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Background: Coronavirus-2019 (COVID-19) vaccination in Australia commenced in February 2021. The first vaccines recommended for use were AZD1222 and BNT162b2, both delivered as a two-dose primary schedule. In the absence of sustained immunity following immunisation, recommendations for booster vaccination have followed. It is likely that periodic boosting will be necessary for at least some Australians, but it is unknown what the optimal booster vaccines and schedules are or for whom vaccination should be recommended. Methods: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, randomised, Bayesian adaptive platform trial evaluating different booster vaccine interventions in immunocompetent children and adults, stratified by their primary vaccination schedule and age. Participants are randomised to receive one of three licensed COVID-19 booster vaccines available for use in Australia. PICOBOO aims to generate evidence about the immunogenicity, reactogenicity, and cross-protection of different booster vaccine strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants/subvariants. The protocol structure specifying PICOBOO is modular and hierarchical. We have previously published the PICOBOO core (master) protocol. Here, we detail the substudy protocol which outlines the study processes which are specific to PICOBOO participants enrolled in the booster vaccination substudy. Discussion: PICOBOO is an adaptive platform trial evaluating different COVID-19 booster vaccination strategies to generate evidence to inform immunisation practice and policy. The modular and flexible protocol structure is intended to enable investigators to respond with agility to new research questions as they arise, such as immunogenicity targeting emergent virus variants, and the immunogenicity and reactogenicity of new vaccines as they become available for use. Trial registration: Australian and New Zealand Clinical Trials Register ACTRN12622000238774; registered on 10/02/2022. Protocol V8.0_23112023. [ABSTRACT FROM AUTHOR]

Introduction: Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear. Methods: We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination. Results: We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti-spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2-producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion. Discussion: Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients. [ABSTRACT FROM AUTHOR]

Background: DS-5670 is a messenger ribonucleic acid (mRNA) vaccine platform targeting the receptor-binding domain (RBD) of the spike protein derived from severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Booster vaccination against coronavirus disease 2019 (COVID-19) with monovalent DS-5670a (incorporating mRNA encoding the RBD from the original SARS-CoV-2 strain) or bivalent DS-5670a/b (original and omicron BA.4-5 RBD antigens) is effective and safe in adults. Data from a phase 2/3 active-controlled, noninferiority, pediatric study evaluating a third booster dose of DS-5670a/b are reported here. Methods: Children aged 5-11 years who had completed the two-dose primary vaccination series with monovalent BNT162b2 (original strain) at least 3 months prior to enrolment were randomly assigned to receive DS-5670a/b (20 µg of mRNA) or bivalent BNT1 62b2 (original/omicron BA.4-5; 10 µg of mRNA) on Day 1. The primary efficacy endpoint was blood neutralization geometric mean titer (GMT) against SARS-CoV-2 (omicron variant BA.5.2.1) and immune response rate (≥ 4-fold increase in post-vaccination circulating anti-SARS-CoV-2 neutralizing activity) on Day 29. Results: Among evaluable participants (DS-5670a/b, n = 74; bivalent BNT162b2, n = 75), the adjusted GMT ratio of DS-5670a/b to bivalent BNT162b2 on Day 29 was 1.636 (95% CI, 1.221, 2.190). Immune response rates were ≥ 89% with both study vaccines; adjusted difference 2.6% (95% CI, -7.8, 13.8). The prespecified non-inferiority margins were exceeded, and the study met the primary endpoint. DS-5670a/b also demonstrated broad neutralization activity across recent omicron sublineages and no cases of COVID-19 between Days 8-29 post-administration were reported. There were no novel safety concerns in the pediatric population at data cut-off. Conclusions: Bivalent DS-5670a/b was non-inferior to bivalent BNT162b2 in terms of immunogenicity, and had a manageable safety profile, when administered as a heterologous booster in children aged 5-11 years. [ABSTRACT FROM AUTHOR]

Abstract Background Coronavirus-2019 (COVID-19) vaccination in Australia commenced in February 2021. The first vaccines recommended for use were AZD1222 and BNT162b2, both delivered as a two-dose primary schedule. In the absence of sustained immunity following immunisation, recommendations for booster vaccination have followed. It is likely that periodic boosting will be necessary for at least some Australians, but it is unknown what the optimal booster vaccines and schedules are or for whom vaccination should be recommended. Methods The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, randomised, Bayesian adaptive platform trial evaluating different booster vaccine interventions in immunocompetent children and adults, stratified by their primary vaccination schedule and age. Participants are randomised to receive one of three licensed COVID-19 booster vaccines available for use in Australia. PICOBOO aims to generate evidence about the immunogenicity, reactogenicity, and cross-protection of different booster vaccine strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants/subvariants. The protocol structure specifying PICOBOO is modular and hierarchical. We have previously published the PICOBOO core (master) protocol. Here, we detail the substudy protocol which outlines the study processes which are specific to PICOBOO participants enrolled in the booster vaccination substudy. Discussion PICOBOO is an adaptive platform trial evaluating different COVID-19 booster vaccination strategies to generate evidence to inform immunisation practice and policy. The modular and flexible protocol structure is intended to enable investigators to respond with agility to new research questions as they arise, such as immunogenicity targeting emergent virus variants, and the immunogenicity and reactogenicity of new vaccines as they become available for use. Trial registration Australian and New Zealand Clinical Trials Register ACTRN12622000238774; registered on 10/02/2022. Protocol V8.0_23112023.

Background: Positive mental health (PMH) response for families who have schizophrenic patients in the implementation of vaccination is a double burden that occurs in efforts to prevent the Covid-19 Virus in schizophrenic patients. Purpose: The study aims to explain Family Psychological Responses to the implementation of booster vaccination in Schizophrenia as a Prevention of Covid-19 based on PMH. Methods: This means Between October and December 2022, there will be 127 families with schizophrenia-afflicted members. This study used a sequential explanatory design with a mixed methodology. PMH scale instrument was employed as the research tool in a community-based adult with the PMH scale's sensitivity. Results: Results of the study findings revealed that the overall PMH questionnaire of PMH scale included 6 items 1) General coping Rural (2.99 ±1.2); Urban (2.27 ±1.1) 2) Emotional support Rural (2.99±1.2); Urban (2.27 ±1.1); 3) Spirituality, Rural (2.99±1.8); Urban (2.29 ± 1.3), 4) Interpersonal Skill highest score Rural (2.99 ± 1.2); Urban (2.27 ±1.1), 5) Personal Growth & Autonomous Rural (2.99 ±1.2); Urban (2.27 ±1.1), 6) Global Affect Rural (2.98 ±1.6); Urban (2.28 ±1.1). Conclusion: PMH psychological responses can occur in the implementation of booster vaccination in families of schizophrenia patients so Along with PMH, Negative Mental Health, and vaccination implementation in families of schizophrenia patients, it is important to pay attention to both (NMH).

Background Diphtheria can be effectively prevented by adequate immunization. A combined vaccine against diphtheria toxoid, pertussis, and tetanus toxoid (DPT) is currently used in routine pediatric immunizations. Outbreaks of diphtheria could emerge in Indonesia as a consequence of declining routine vaccination during the COVID-19 pandemic. Objective To analyze the impact of the first (administered at 18-24 months of age ) and second diphtheria boosters (administered at 5-7 years of age ) in retaining protective levels of anti-diphtheria toxoid antibodies. We also investigated for relevant factors associated with anti-diphtheria toxoid antibody titers. Methods This cross-sectional study was conducted in the Senen District of Jakarta, Indonesia. The inclusion criteria were healthy children aged 6 to 7 years with documented history of DPT vaccination. Primary vaccination defined as 3 doses of DPT at age less than 1 year , first booster was DPT vaccination at 18-24 years of age, and second booster was diphtheria-tetanus (DT) vaccination received at 5 to 7 years of age. Peripheral blood specimens were obtained from participating children, after informed consent was provided by their parents. Antibodies against diphtheria in sera specimens were assessed by commercial anti-diphtheria toxoid immunoglobulin G (IgG) enzyme-linked immunosorbent assay. Results There were 154 children included in the study, with a female majority (61%). Overall, specific humoral immunity against diphtheria was observed in 113 children (73.4%). There was no statistical difference in immunity level between genders. Importantly, children who received the first and second diphtheria booster had significantly higher anti-diphtheria antibody level than those who did not receive both diphtheria booster (P

Abstract Formative research is an important component of health communication campaign development. Rapid message testing approaches are useful for testing new messaging quickly and efficiently during public health emergencies, such as COVID-19, when guidance and recommendations are rapidly changing. Wiki surveys simultaneously collect quantitative message testing data and qualitative feedback on potential social media campaign messages. Philly CEAL used wiki surveys to test messages about COVID-19 vaccinations for dissemination on social media. A cross-sectional survey of Philadelphia residents (N = 199) was conducted between January and March 2023. Wiki surveys were used to assess the perceived effectiveness of messages promoting the updated COVID-19 booster and child vaccination. In each wiki survey, participants were presented with two messages and asked to select the one that they perceived as most effective. Participants could alternatively select “can’t decide” or submit their own message. A score estimating the probability of selection was calculated for each message. Participant-generated messages were routinely reviewed and incorporated into the message pool. Participants cast a total of 32,281 votes on messages seeded by the research team (n = 20) and participants (n = 43). The highest scoring messages were those that were generated by participants and spoke to getting your child vaccinated to protect them against serious illness and getting the booster to protect your health and that of your community. These messages were incorporated into social media posts disseminated by Philly CEAL’s social media accounts. Wiki surveys are a feasible and efficient method of rapid message testing for social media campaigns.

Background: Real-world vaccine effectiveness following the third dose of vaccination against SARS-CoV-2 remains less investigated among people with HIV (PWH). Methods: PWH receiving the third dose of BNT162b2 and mRNA-1273 (either 50- or 100-μg) were enrolled. Participants were followed for 180 days until the fourth dose of COVID-19 vaccination, SARS-CoV-2 infection, seroconversion of anti-nucleocapsid IgG, death, or loss to follow-up. Anti-spike IgG was determined every 1–3 months. Results: Of 1427 participants undergoing the third-dose COVID-19 vaccination, 632 (44.3%) received 100-μg mRNA-1273, 467 (32.8%) 50-μg mRNA-1273, and 328 (23.0%) BNT162b2 vaccine and the respective rate of SARS-CoV-2 infection or seroconversion of anti-nucleocapsid IgG was 246.1, 280.8 and 245.2 per 1000 person-months of follow-up (log-rank test, p = 0.28). Factors associated with achieving anti-S IgG titers >1047 BAU/mL included CD4 count 200 copies/mL (aOR, 0.27; 95% CI, 0.09–0.80), having achieved anti-spike IgG >141 BAU/mL within 3 months after primary vaccination (aOR, 3.69; 95% CI, 2.68–5.07), receiving BNT162b2 vaccine as the third dose (aOR, 0.20; 95% CI, 0.10–0.41; reference, 100-μg mRNA-1273), and having previously received two doses of mRNA vaccine in primary vaccination (aOR, 2.46; 95% CI, 1,75-3.45; reference, no exposure to mRNA vaccine). Conclusions: PWH receiving different types of the third dose of COVID-19 vaccine showed similar vaccine effectiveness against SARS-CoV-2 infection. An additional dose with 100-μg mRNA-1273 could generate a higher antibody response than with 50-μg mRNA-1273 and BNT162b2 vaccine.

Abstract Background Scale drop disease virus (SDDV) threatens Asian seabass (Lates calcarifer) aquaculture production by causing scale drop disease (SDD) in Asian seabass. Research on the development of SDDV vaccines is missing an in-depth examination of long-term immunity and the immune reactions it provokes. This study investigated the long-term immune protection and responses elicited by an SDDV vaccine. The research evaluated the effectiveness of a formalin-inactivated SDDV vaccine (SDDV-FIV) using both prime and prime-booster vaccination strategies in Asian seabass. Three groups were used: control (unvaccinated), single-vaccination (prime only), and booster (prime and booster). SDDV-FIV was administered via intraperitoneal route, with a booster dose given 28 days post-initial vaccination. Results The immune responses in vaccinated fish (single and booster groups) showed that SDDV-FIV triggered both SDDV-specific IgM and total IgM production. SDDV-specific IgM levels were evident until 28 days post-vaccination (dpv) in the single vaccination group, while an elevated antibody response was maintained in the booster group until 70 dpv. The expression of immune-related genes (dcst, mhc2a1, cd4, ighm, cd8, il8, ifng, and mx) in the head kidney and peripheral blood lymphocytes (PBLs) of vaccinated and challenged fish were significantly upregulated within 1–3 dpv and post-SDDV challenge. Fish were challenged with SDDV at 42 dpv (challenge 1) and 70 dpv (challenge 2). In the first challenge, the group that received booster vaccinations demonstrated notably higher survival rates than the control group (60% versus 20%, P 0.05). These findings suggest that the SDDV-FIV vaccine effectively stimulates both humoral and cellular immune responses against SDDV. Booster vaccination enhances this response and improves survival rates up to 42 dpv. Conclusions This research provides valuable insights into the development of efficient SDDV vaccines and aids in advancing strategies for immune modulation to enhance disease management in the aquaculture of Asian seabass.

Formative research is an important component of health communication campaign development. Rapid message testing approaches are useful for testing new messaging quickly and efficiently during public health emergencies, such as COVID-19, when guidance and recommendations are rapidly changing. Wiki surveys simultaneously collect quantitative message testing data and qualitative feedback on potential social media campaign messages. Philly CEAL used wiki surveys to test messages about COVID-19 vaccinations for dissemination on social media. A cross-sectional survey of Philadelphia residents (N = 199) was conducted between January and March 2023. Wiki surveys were used to assess the perceived effectiveness of messages promoting the updated COVID-19 booster and child vaccination. In each wiki survey, participants were presented with two messages and asked to select the one that they perceived as most effective. Participants could alternatively select "can't decide" or submit their own message. A score estimating the probability of selection was calculated for each message. Participant-generated messages were routinely reviewed and incorporated into the message pool. Participants cast a total of 32,281 votes on messages seeded by the research team (n = 20) and participants (n = 43). The highest scoring messages were those that were generated by participants and spoke to getting your child vaccinated to protect them against serious illness and getting the booster to protect your health and that of your community. These messages were incorporated into social media posts disseminated by Philly CEAL's social media accounts. Wiki surveys are a feasible and efficient method of rapid message testing for social media campaigns. [ABSTRACT FROM AUTHOR]

Postacute symptoms are not uncommon after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with pre-Omicron variants. How the Omicron variant and coronavirus disease 2019 (COVID-19) booster vaccination influence the risk of postacute symptoms is less clear. We analyzed data from a nationwide Danish questionnaire study, EFTER-COVID, comprising 36 109 individuals aged ≥15 years who were tested between July 2021 and January 2022, to evaluate the associations of the Omicron variant and COVID-19 booster vaccination with postacute symptoms and new-onset general health problems 4 months after infection with SARS-CoV-2. Risk differences (RDs) were estimated by comparing Omicron cases with controls, comparing Omicron cases with Delta cases, and comparing Omicron cases vaccinated with 3 doses with those vaccinated with 2 doses, adjusting for age, sex, body mass index, self-reported chronic diseases, Charlson comorbidity index, health-care occupation, and vaccination status. Four months after testing for SARS-CoV-2 during the Omicron period, cases experienced substantial postacute symptoms and new-onset health problems in comparison with controls; the largest RD was observed for memory issues (RD = 7.4%; 95% CI, 6.4-8.3). However, risks were generally lower than those in the Delta period, particularly for dysosmia (RD = –15.0%; 95% CI, −17.0 to −13.2) and dysgeusia (RD = –11.2%; 95% CI, −13.2 to −9.5). Booster vaccination was associated with fewer postacute symptoms and new-onset health problems 4 months after Omicron infection as compared with 2 doses of COVID-19 vaccine. [ABSTRACT FROM AUTHOR]

Background: Scale drop disease virus (SDDV) threatens Asian seabass (Lates calcarifer) aquaculture production by causing scale drop disease (SDD) in Asian seabass. Research on the development of SDDV vaccines is missing an in-depth examination of long-term immunity and the immune reactions it provokes. This study investigated the long-term immune protection and responses elicited by an SDDV vaccine. The research evaluated the effectiveness of a formalin-inactivated SDDV vaccine (SDDV-FIV) using both prime and prime-booster vaccination strategies in Asian seabass. Three groups were used: control (unvaccinated), single-vaccination (prime only), and booster (prime and booster). SDDV-FIV was administered via intraperitoneal route, with a booster dose given 28 days post-initial vaccination. Results: The immune responses in vaccinated fish (single and booster groups) showed that SDDV-FIV triggered both SDDV-specific IgM and total IgM production. SDDV-specific IgM levels were evident until 28 days post-vaccination (dpv) in the single vaccination group, while an elevated antibody response was maintained in the booster group until 70 dpv. The expression of immune-related genes (dcst, mhc2a1, cd4, ighm, cd8, il8, ifng, and mx) in the head kidney and peripheral blood lymphocytes (PBLs) of vaccinated and challenged fish were significantly upregulated within 1–3 dpv and post-SDDV challenge. Fish were challenged with SDDV at 42 dpv (challenge 1) and 70 dpv (challenge 2). In the first challenge, the group that received booster vaccinations demonstrated notably higher survival rates than the control group (60% versus 20%, P < 0.05). However, in the second challenge, while there was an observable trend towards improved survival rates for the booster group compared to controls (42% versus 25%), these differences did not reach statistical significance (P > 0.05). These findings suggest that the SDDV-FIV vaccine effectively stimulates both humoral and cellular immune responses against SDDV. Booster vaccination enhances this response and improves survival rates up to 42 dpv. Conclusions: This research provides valuable insights into the development of efficient SDDV vaccines and aids in advancing strategies for immune modulation to enhance disease management in the aquaculture of Asian seabass. [ABSTRACT FROM AUTHOR]

Kidney transplant recipients (KTRs), like other solid organ transplant recipients display a suboptimal response to mRNA vaccines, with only about half achieving seroconversion after two doses. However, the effectiveness of a booster dose, particularly in generating neutralizing antibodies (NAbs), remains poorly understood, as most studies have mainly focused on non‐neutralizing antibodies. Here, we have longitudinally assessed the humoral response to the SARS‐CoV‐2 mRNA vaccine in 40 KTRs over a year, examining changes in both anti‐spike IgG and NAbs following a booster dose administered about 5 months post‐second dose. We found a significant humoral response increase 5 months post‐booster, a stark contrast to the attenuated response observed after the second dose. Of note, nearly a quarter of participants did not achieve protective plasma levels even after the booster dose. We also found that the higher estimated glomerular filtration rate (eGFR) correlated with a more robust humoral response postvaccination. Altogether, these findings underscore the effectiveness of the booster dose in enhancing durable humoral immunity in KTRs, as evidenced by the protective level of NAbs found in 65% of the patients 5 months post‐ booster, especially those with higher eGFR rates. [ABSTRACT FROM AUTHOR]

Early studies have found that the initial COVID-19 vaccination series was protective against severe symptoms and long COVID. However, few studies have explored the association of booster doses on severe disease outcomes and long COVID. This cross-sectional analysis used data from the 2022 US National Health Interview Survey data to investigate how vaccination status correlates with COVID-19 infection severity and long COVID among previously infected individuals. Participants were categorized into three groups: those who had received at least one booster, those with only the initial complete vaccination series, and those with either an incomplete series or no vaccinations. Out of 9521 survey respondents who reported a past positive COVID-19 test, 51.2% experienced moderate/severe infections, and 17.6% experienced long COVID. Multivariable regression models revealed that receiving at least one booster shot was associated with lower odds of experiencing moderate/severe symptoms (aOR = 0.78, p < 0.001) compared to those unvaccinated or with an incomplete series. Additionally, having at least one booster reduced long COVID odds by 24% (aOR = 0.76, p = 0.003). Completing only the primary vaccine series did not significantly decrease the likelihood of severe illness or long COVID. These findings support the continued promotion of booster vaccinations to mitigate long COVID risks in vulnerable populations. [ABSTRACT FROM AUTHOR]

IntroductionSolid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear.MethodsWe investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination.ResultsWe corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti- spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2- producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion.DiscussionOur study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients.

Objectives: To assess the safety and immunogenicity of a fourth vaccination (second booster) in individuals aged ≥75 years. Methods: Participants were randomized to BNT162b2 (Comirnaty, 30 µg) or messenger RNA (mRNA)-1273 (Spikevax, 100 µg). The primary end point was the rate of two-fold antibody titer increase 14 days after vaccination, targeting the receptor binding domain (RBD) region of wild-type SARS-CoV-2. The secondary end points included changes in neutralizing activity against wild-type and 25 variants. Safety was assessed by monitoring solicited adverse events (AEs) for 7 days. Results: A total of 269 participants (mean age 81 years, mRNA-1273 n = 135/BNT162b2 n = 134) were included. Two-fold anti-RBD immunoglobulin (Ig) G titer increase was achieved by 101 of 129 (78%) and 116 of 133 (87%) subjects in the BNT162b2 and the mRNA-1273 group, respectively (P = 0.054). A second booster of mRNA-1273 provided higher anti-RBD IgG geometric mean titer: 21.326 IU/mL (95% confidence interval: 18.235-24.940) vs BNT162b2: 15.181 IU/mL (95% confidence interval: 13.172-17.497). A higher neutralizing activity was noted for the mRNA-1273 group. The most frequent AE was pain at the injection site (51% in mRNA-1273 and 48% in BNT162b2). Participants in the mRNA-1273 group had less vaccine-related AEs (30% vs 39%). Conclusions: A second booster of either BNT162b2 or mRNA-1273 provided substantial IgG increase. Full-dose mRNA-1273 provided higher IgG levels and neutralizing capacity against SARS-CoV-2, with similar safety profile for subjects of advanced age.

Abstract Despite the high efficacy and safety demonstrated in clinical trials, COVID-19 booster vaccination rates in Malaysia remain below 50% among the general public. This study explores the factors influencing public acceptance of the COVID-19 booster vaccine among the Malaysian population. The questionnaire included variables on sociodemographics, knowledge, and the Health Belief Model (HBM) constructs. Based on the Chi-squared test of contingencies, a t-test and multivariate logistic regression analysis on 411 collected responses, the findings revealed that older participants, individuals of Chinese ethnicity, and those with higher education levels and incomes were more willing to accept booster vaccinations. The analysis further identified perceived susceptibility, perceived severity and perceived barriers as significant predictors influencing booster vaccination acceptance rates. Healthcare policymakers may consider targeting interventions to diminish the obstacles associated with booster vaccinations. These intervention strategies include implementing health intervention programmes, such as public health awareness initiatives, to raise awareness of the risks and severity of COVID-19, ultimately encouraging higher uptake of booster vaccines.

Purpose: Previous studies have demonstrated that the majority of patients with an inborn error of immunity (IEI) develop a spike (S)-specific IgG antibody and Tcell response after two doses of the mRNA-1273 COVID-19 vaccine, but little is known about the response to a booster vaccination. We studied the immune responses 8 weeks after booster vaccination with mRNA-based COVID-19 vaccines in 171 IEI patients. Moreover, we evaluated the clinical outcomes in these patients one year after the start of the Dutch COVID-19 vaccination campaign. Methods: This study was embedded in a large prospective multicenter study investigating the immunogenicity of COVID-19 mRNA-based vaccines in IEI (VACOPID study). Blood samples were taken from 244 participants 8 weeks after booster vaccination. These participants included 171 IEI patients (X-linked agammaglobulinemia (XLA;N=11), combined immunodeficiency (CID;N=4), common variable immunodeficiency (CVID;N=45), isolated or undefined antibody deficiencies (N=108) and phagocyte defects (N=3)) and 73 controls. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T-cell responses were evaluated. One year after the start of the COVID-19 vaccination program, 334 study participants (239 IEI patients and 95 controls) completed a questionnaire to supplement their clinical data focusing on SARS-CoV-2 infections. Results: After booster vaccination, S-specific IgG titers increased in all COVID-19 naive IEI cohorts and controls, when compared to titers at 6 months after the priming regimen. The fold-increases did not differ between controls and IEI cohorts. SARS-CoV-2-specific T-cell responses also increased equally in all cohorts after booster vaccination compared to 6 months after the priming regimen. Most SARS-CoV-2 infections during the study period occurred in the period when the Omicron variant had become dominant. The clinical course of these infections was mild, although IEI patients experienced more frequent fever and dyspnea compared to controls and their symptoms persisted longer. Conclusion: Our study demonstrates that mRNA-based booster vaccination induces robust recall of memory B-cell and T-cell responses in most IEI patients. One-year clinical follow-up demonstrated that SARS-CoV-2 infections in IEI patients were mild. Given our results, we support booster campaigns with newer variant-specific COVID-19 booster vaccines to IEI patients with milder phenotypes. [ABSTRACT FROM AUTHOR]

After the termination of zero‐COVID‐19 policy, the populace in China has experienced both Omicron BA.5 and XBB waves. Considering the poor antibody responses and severe outcomes observed among the elderly following infection, we conducted a longitudinal investigation to examine the epidemiological characteristics and antibody kinetics among 107 boosted elderly participants following the Omicron BA.5 and XBB waves. We observed that 96 participants (89.7%) were infected with Omicron BA.5, while 59 (55.1%) participants were infected with Omicron XBB. Notably, 52 participants (48.6%) experienced dual infections of both Omicron BA.5 and XBB. The proportion of symptomatic cases appeared to decrease following the XBB wave (18.6%) compared to that after the BA.5 wave (59.3%). Omicron BA.5 breakthrough infection induced lower neutralizing antibody titers against XBB.1.5, BA.2.86, and JN.1, while reinfection with Omicron XBB broadened the antibody responses against all measured Omicron subvariants and may alleviate the wild type‐vaccination induced immune imprinting. Boosted vaccination type and comorbidities were the significant factors associated with antibody responses. Updated vaccines based on emerging severe acute respiratory syndrome coronavirus 2 variants are needed to control the Coronavirus Disease 2019 pandemic in the elderly. [ABSTRACT FROM AUTHOR]

Hungary provides the opportunity to evaluate the effectiveness of COVID-19 vaccination in a setting where naturally acquired immunity and hybrid immunity are likely to play a greater role due to suboptimal vaccination coverage. Methods: A test-negative study was conducted during the 2022–2023 respiratory season at the primary care level to determine the effectiveness of at least one COVID-19 booster dose in preventing medically attended symptomatic RT-PCR-confirmed SARS-CoV-2 infection in adults. Unvaccinated patients were used as a reference group. Results: A total of 247 cases and 1073 controls were included in the analysis. CVE was 56.8% (95% CI: 11.9–78.8%) in the population aged 60 years and older and 2.3% (95% CI: −50.0–36.3%) in the younger adults against COVID-19 caused by Omicron subvariants, mainly BA.5, BQ.1, and XBB.1. Self-reported COVID-19 in the 60–365 days prior to the current illness did not confer protection against reinfection without vaccination, but together with booster vaccination, it reduced the risk of COVID-19 by 63.0% (95% CI: −28.0–89.3%) and 87.6% (95% CI: 26.4–97.9%) among the 18–59 and 60+ age groups, respectively. Conclusions: CVE against COVID-19 was moderately high in the 60+ age groups. Because of the benefit of hybrid immunity, persons with previous SARS-CoV-2 infection should still be considered for vaccination campaigns. [ABSTRACT FROM AUTHOR]

Understanding the association between booster vaccination and COVID-19 outcomes can help strengthen post-pandemic messaging and strategies to increase vaccination and reduce severe and long-term consequences of COVID-19. Using the Household Pulse Survey data collected from U.S. adults from 9 December 2022 to 13 February 2023 (n = 214,768), this study assessed the relationship between COVID-19 booster vaccination and COVID-19 outcomes (testing positive for COVID-19, moderate/severe COVID-19, and long COVID). Disparities were found in COVID-19 outcomes (e.g., testing positive for COVID-19, moderate/severe COVID-19, and long COVID) by sociodemographic characteristics, region of residence, food insecurity status, mental health status, disability status, and housing type. Receipt of a COVID-19 booster vaccination was negatively associated with testing positive for COVID-19 (aOR = 0.75, 95%CI: 0.72,0.79), having moderate/severe COVID-19 (aOR = 0.92, 95%CI: 0.88, 0.97), or having long COVID (aOR = 0.86 (0.80, 0.91)). Even among those who tested positive for COVID-19, those who received the booster vaccine were less likely to have moderate/severe COVID-19 and less likely to have long COVID. Communicating the benefits of COVID-19 booster vaccination, integrating vaccination in patient visits, and reducing access barriers can increase vaccination uptake and confidence for all individuals and protect them against the severe negative outcomes of COVID-19. [ABSTRACT FROM AUTHOR]

Despite the high efficacy and safety demonstrated in clinical trials, COVID-19 booster vaccination rates in Malaysia remain below 50% among the general public. This study explores the factors influencing public acceptance of the COVID-19 booster vaccine among the Malaysian population. The questionnaire included variables on sociodemographics, knowledge, and the Health Belief Model (HBM) constructs. Based on the Chi-squared test of contingencies, a t-test and multivariate logistic regression analysis on 411 collected responses, the findings revealed that older participants, individuals of Chinese ethnicity, and those with higher education levels and incomes were more willing to accept booster vaccinations. The analysis further identified perceived susceptibility, perceived severity and perceived barriers as significant predictors influencing booster vaccination acceptance rates. Healthcare policymakers may consider targeting interventions to diminish the obstacles associated with booster vaccinations. These intervention strategies include implementing health intervention programmes, such as public health awareness initiatives, to raise awareness of the risks and severity of COVID-19, ultimately encouraging higher uptake of booster vaccines. [ABSTRACT FROM AUTHOR]

Immunomodulatory and immunosuppressive therapy is needed in people with a chronic neuroinflammatory disease of the central nervous system such as multiple sclerosis (MS). Therefore, MS requires monitoring for and preventing against infectious diseases like SARS-CoV-2. Vaccination and anti-viral treatments are, in particular, recommended for elderly people and people at risk of a severe course of infection and of MS. Here, we asked whether repetitive infection or vaccination influenced responses upon receiving high efficacy treatments, namely sphingosine-1-phosphate receptor modulator (S1P) or anti-CD20 B cell antibody (anti-CD20) treatments. We performed a prospective real-world study of people with MS (pwMS) under S1P or anti-CD20 with repetitive exposure to the SARS-CoV-2 virus or vaccine. The measurement of anti-SARS-CoV-2 antibody titres was performed by two independent immunoassays after initial immunisation and after booster vaccination or infection. Other laboratory and clinical parameters were included in the analysis of influencing factors. As secondary outcomes, lymphocyte and immunoglobulin levels were observed longitudinally under intravenous and subcutaneous anti-CD20 treatment. In a long-term real-world cohort of 201 pwMS, we found that despite lymphopenia upon S1P drugs, the SARS-CoV-2 immunisation response increased both in selective and non-selective S1P (100% and 88% seroconversion, respectively), whereas those under anti-CD20 therapies merely exhibited a slight long-term increase in antibody titres (52% seroconversion). The latter was independent of immunoglobulin or total lymphocyte levels, which mostly remained stable. If the individual was immunised prior to therapy initiation, their levels of SARS-CoV-2 antibodies remained high under treatment. PwMS under non-selective S1P benefit from repetitive vaccination. The risk of an insufficient vaccination response mirrored by lower SARS-CoV-2 antibodies remains in pwMS receiving anti-CD20 treatment, even after repetitive exposure to the vaccine or virus. Due to the compromised vaccination response in CD20-depleting drugs, prompt antiviral treatment might be necessary. [ABSTRACT FROM AUTHOR]

Abstract Background Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. Methods The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants’ demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. Results A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415–0.823) and older age (HR = 0.974, 95%CI 0.966–0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949–0.977). Female sex (HR = 2.570, 95%CI1.435–4.603), smoking (HR = 1.965, 95%CI1.147–3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465–5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. Conclusion The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. Trial registration DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021.

Background: To date, few studies from the Asian region have reported the effectiveness of messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccines against disease progression and death after hospitalization. Methods: We evaluated the data from the COVID-19 registry in Japan during the delta- and omicron-dominant phases. A propensity score-matched cohort study was conducted between the incompletely (0–1 dose) and fully (2 doses) vaccinated groups during the delta-dominant phase and among the incompletely, fully, and booster (3 doses) vaccinated groups during the omicron-dominant phase. Results: In the delta-dominant phase, 411 pairs were matched. The fully vaccinated group showed a significantly lower oxygen supplementation rate (24.1 % vs. 41.1 %, p

Background: Amidst the COVID-19 pandemic, vaccination has been a crucial strategy for mitigating transmission and disease severity. However, vaccine-effectiveness may be influenced by various factors, including booster vaccination, as well as personal factors such as age, sex, BMI, smoking, and comorbidities. To investigate the potential effects of these factors on SARS-CoV-2 infection and disease severity, we analyzed data from the third round of the Cologne Corona Surveillance (CoCoS) project, a large cross-sectional survey. Methods: The study was conducted mid-February to mid-March 2022 in Cologne, Germany. A random sample of 10,000 residents aged 18 years and older were invited to participate in an online survey. Information on participants' demographics (age, sex), SARS-CoV-2 infections, vaccination status, smoking, and preexisting medical conditions were collected. The outcomes of the study were: (1) the occurrence of SARS-CoV-2 infection despite vaccination (breakthrough infection) and (2) the occurrence of moderate-to-severe disease as a result of a breakthrough infection. Cox proportional-hazards regression was used to investigate possible associations between the presence/absence of booster vaccination, personal factors and the occurrence of SARS-CoV-2 infection. Associations with moderate-to-severe infection were analyzed using the Fine and Gray subdistribution hazard model. Results: A sample of 2,991 residents responded to the questionnaire. A total of 2,623 primary immunized participants were included in the analysis of breakthrough infection and 2,618 in the analysis of SARS-CoV-2 infection severity after exclusions due to incomplete data. The multivariable results show that booster vaccination (HR = 0.613, 95%CI 0.415–0.823) and older age (HR = 0.974, 95%CI 0.966–0.981) were associated with a reduced hazard of breakthrough infection. Regarding the severity of breakthrough infection, older age was associated with a lower risk of moderate-to-severe breakthrough infection (HR = 0.962, 95%CI0.949–0.977). Female sex (HR = 2.570, 95%CI1.435–4.603), smoking (HR = 1.965, 95%CI1.147–3.367) and the presence of chronic lung disease (HR = 2.826, 95%CI1.465–5.450) were associated with an increased hazard of moderate-to-severe breakthrough infection. Conclusion: The results provide a first indication of which factors may be associated with SARS-CoV-2 breakthrough infection and moderate-to-severe course of infection despite vaccination. However, the retrospective nature of the study and risk of bias in the reporting of breakthrough infection severity limit the strength of the results. Trial registration: DRKS.de, German Clinical Trials Register (DRKS), Identifier: DRKS00024046, Registered on 25 February 2021. [ABSTRACT FROM AUTHOR]

• RA patients showed lower IgG-anti-TBEV compared to HC. • In RA, IgG-anti-TBEV are influenced by age at, time since last TBEV vaccination and disease duration. • Higher IgG-anti-TBEV responses in RA patients who had received booster vaccination. • Lower natural killer cell responses in RA patients. • Immunological benefits are suggested for timely boosters. Inactivated vaccines, such as tick-borne-encephalitis-virus-(TBEV) vaccine, have been discussed as less immunogenic in elderly and in immunocompromised patients. In this controlled cross-sectional cohort study, the antibody and cellular responses after TBEV-vaccination were investigated in 36 rheumatoid arthritis (RA) patients and 112 healthy controls (HC) by evaluating IgG-anti-TBEV concentration, neutralization and relative avidity index (RAI). Cellular reactivity was assessed by IFNgamma-producing spot-forming-units (SFU) by ELISPOT assay and flow cytometry. RA patients showed lower IgG-anti-TBEV compared to HC, which were influenced by age at and time since last TBEV vaccination and disease duration. High-responders regarding cellular immunity and avidity were less frequent in RA compared to HC. RA patients who had received booster vaccinations were more likely to demonstrate higher IgG-anti-TBEV responses compared to those who had not. In conclusion, RA patients showed a negative effect of age on anti-TBEV-IgG and immunological benefits of timely booster vaccination are suggested. [ABSTRACT FROM AUTHOR]

• Study of determinants of COVID-19 autumn booster uptake in risk groups in the Netherlands. • Booster uptake was 68 % among people ≥ 60 years and 30 % among medical risk group 18–59 years. • Most important determinant for booster uptake in both target groups was age. • Political preference, migration status and household type are important determinants. • Findings are important for future campaigns targeting people at increased risk of severe COVID-19. A booster with bivalent COVID-19 vaccine was offered in the Netherlands in autumn, 2022. We aimed to investigate vaccine uptake during the autumn 2022 booster round among the population subgroups at risk for severe COVID-19 that were specifically targeted by this campaign: the medical risk group aged 18–59 years and individuals ≥ 60 years. We calculated booster uptake in both populations and analyzed determinants of booster uptake among those who had received at least one prior COVID-19 vaccination. Having had an autumn 2022 booster dose was defined as having received a COVID-19 vaccination between 19 September 2022 and 7 March 2023. The study population included individuals who received at least one previous COVID-19 vaccination. National registries of sociodemographic determinants and COVID-19 vaccination were linked by a unique person identifier. Voting proportions for political parties were included at neighborhood level. Determinants of COVID-19 vaccine autumn booster uptake were ranked by importance by random forest analyses. Booster uptake was 68 % among those aged ≥ 60 and 30 % among those aged 18–59 years with a medical risk factor for severe disease. For both target groups the most important determinant for booster uptake was age (15 % in 18–29 years to 72 % in 80 + years). Voting proportions for progressive liberal political parties ranked second in the random forest analysis in both groups, with an increasing proportion of votes associated with higher uptake. In the 60 + group, household type ranked third, with highest vaccine uptake among married couples without children (72 %) and the lowest uptake among unmarried couples with children (47 %). In the medical risk group, migration status ranked third. Migrants with two parents born abroad had the lowest uptake (18 %), whereas migrants with both parents born in the Netherlands had the highest uptake (35 %). The target group of people aged ≥ 60 years was much better reached than the target group of people with a medical risk aged 18–59 years. Uptake varied considerably among subgroups in both target groups. The findings of this study can be used in future vaccination strategies as well as for further research to better understand the drivers and barriers of vaccine uptake among the subgroups with notably low uptake. [ABSTRACT FROM AUTHOR]

Although the pandemic has ended officially, COVID-19 remains impactful. Booster COVID-19 vaccination is still needed to protect individuals against COVID-19 and the disease's harmful consequences. This study investigated the prevalence of the intention to get booster COVID-19 vaccination after receiving the COVID-19 diagnosis and its associated factors among people reporting prior COVID-19. A population-based anonymous telephone survey was conducted in Hong Kong, China from June to August 2022 among Chinese people reporting prior COVID-1 between February and August 2022 and having taken up ≥2 doses of COVID-19 vaccines prior to COVID-19 diagnosis. The prevalence of the intention to get booster vaccination was 59.2 %. Older age (>60 years), being currently married, not employed full-time, and having chronic diseases were positively associated with the intention to get booster vaccination. Adjusted for the background factors, higher levels of the cognitive factors of perceived susceptibility to COVID-19, perceived acquired moderate-to-strong immunity against COVID-19, and perceived adequate knowledge of COVID-19 were positively associated with the intention to get booster vaccination; stronger perceived severity of prior infection despite vaccination was negatively associated with the intention outcome. In contrast, stronger mental distress due to COVID-19, illness concern, and emotional representation were positively associated with the intention. Self-perceived long COVID status was not a significant factor. The prevalence of the intention to get booster COVID-19 vaccination was limited, especially among younger people reporting prior COVID-19. Health promotion is still required among people reporting prior COVID-19 and may emphasize the significant cognitive factors positively associated with the intention. Future studies are needed to confirm the findings, clarify the role of emotional factors on booster vaccination, and explore other factors of the intention to get booster vaccination among people reporting prior COVID-19. [ABSTRACT FROM AUTHOR]

During the post-coronavirus disease (COVID-19) era, a primary question is whether booster vaccination is effective against severe COVID-19 and should be recommended, particularly to individuals at high risk for severe disease (i.e., the elderly or those with additional severe comorbidities). From December 2020 to February 2023, a cohort study was conducted to estimate IgG and IgA immunogenicity and the dynamics of booster mono- and bivalent COVID-19 mRNA vaccines in 260 individuals (male/female: 114/146, median age: 68 years, interquartile range (IQR) = 31) who initially received either mRNA (218) or adenovirus-vector-based vaccines (42). Participants were followed until the 90th day after the third booster dose. Our cohort study indicated a beneficial effect of booster vaccination on the magnitude of IgG and IgA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We found that second and third booster doses were more protective than one against fatal disease (p = 0.031, OR 0.08). In conclusion, booster COVID-19 vaccination should be strongly recommended, especially to individuals at high risk for severe/fatal disease. [ABSTRACT FROM AUTHOR]

The 3-dose COVID-19 vaccine (booster vaccination) has been offered worldwide. As booster vaccinations continue, it is important to understand the antibody dynamics elicited by booster vaccination in order to evaluate and develop vaccination needs and strategies. Here, we investigated longitudinal data by monitoring IgG antibodies against the receptor binding domain (RBD) in health care workers. We extended our previously developed mathematical model to booster vaccines and successfully fitted antibody titers over time in the absence and presence of past SARS-CoV-2 infection. Quantitative analysis using our mathematical model indicated that anti-RBD IgG titers increase to a comparable extent after booster vaccination, regardless of the presence or absence of infection, but infection history extends the duration of antibody response by 1.28 times. Such a mathematical modeling approach can be used to inform future vaccination strategies on the basis of an individual's immune history. Our simple quantitative approach can be extended to any kind of vaccination and therefore can form a basis for policy decisions regarding the distribution of booster vaccines to strengthen immunity in future pandemics. [ABSTRACT FROM AUTHOR]

Since the onset of the COVID-19 pandemic in March 2020, over 769 million confirmed COVID-19 cases, including close to 7 million COVID-19-related deaths, have been reported. Although mortality rates have dropped notably compared to the first months of the pandemic, spikes in reported cases and mortality rates continue to be registered. Both recent spikes in case numbers and the continued emergence of new variants suggest that vulnerable patient groups, including older adults, immunocompromised patients, and patients with severe comorbidities, are going to continue to be affected by COVID-19. In order to curb the pandemic, relieve the pressure on primary care facilities, and reduce mortality rates, global vaccination programs have been established by the WHO, with over 13.5 billion vaccine doses having been administered globally. In most immunocompetent individuals, vaccination against COVID-19 results in the production of anti-SARS-CoV-2 spike antibodies. However, certain patient subsets have inadequate or reduced immune responses, and immune responses are known to decrease with age. General recommendations on the timing of booster vaccinations may therefore be insufficient to protect vulnerable patients. This review aims to evaluate the clinical role of anti-SARS-CoV-2 antibodies, focusing on measurement indications, prognostic value, and potential as a correlate of protection to guide future booster vaccination strategies. [ABSTRACT FROM AUTHOR]

Background Continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outpaces monovalent vaccine cross-protection to new viral variants. Consequently, bivalent coronavirus disease 2019 (COVID-19) vaccines including Omicron antigens were developed. The contrasting immunogenicity of the bivalent vaccines and the impact of prior antigenic exposure on new immune imprinting remains to be clarified. Methods In the large prospective ENFORCE cohort, we quantified spike-specific antibodies to 5 Omicron variants (BA.1 to BA.5) before and after BA.1 or BA.4/5 bivalent booster vaccination to compare Omicron variant-specific antibody inductions. We evaluated the impact of previous infection and characterized the dominant antibody responses. Results Prior to the bivalent fourth vaccine, all participants (N = 1697) had high levels of Omicron-specific antibodies. Antibody levels were significantly higher in individuals with a previous polymerase chain reaction positive (PCR+) infection, particularly for BA.2-specific antibodies (geometric mean ratio [GMR] 6.79, 95% confidence interval [CI] 6.05–7.62). Antibody levels were further significantly boosted in all individuals by receiving either of the bivalent vaccines, but greater fold inductions to all Omicron variants were observed in individuals with no prior infection. The BA.1 bivalent vaccine generated a dominant response toward BA.1 (adjusted GMR 1.31, 95% CI 1.09–1.57) and BA.3 (1.32, 1.09–1.59) antigens in individuals with no prior infection, whereas the BA.4/5 bivalent vaccine generated a dominant response toward BA.2 (0.87, 0.76–0.98), BA.4 (0.85, 0.75–0.97), and BA.5 (0.87, 0.76–0.99) antigens in individuals with a prior infection. Conclusions Vaccination and previous infection leave a clear serological imprint that is focused on the variant-specific antigen. Importantly, both bivalent vaccines induce high levels of Omicron variant-specific antibodies, suggesting broad cross-protection of Omicron variants. [ABSTRACT FROM AUTHOR]

Booster COVID-19 vaccines have shown efficacy in clinical trials and effectiveness in real-world data against symptomatic and severe illness. However, some people still become infected with SARS-CoV-2 following a third (booster) vaccination. This study describes the characteristics of SARS-CoV-2 illness following a third vaccination and assesses the risk of progression to symptomatic disease in SARS-CoV-2 infected individuals with time since vaccination. This prospective, community-based, case-control study used data from UK-based, adult (≥18 years) users of the COVID Symptom Study mobile application, self-reporting a first positive COVID-19 test between June 1, 2021 and April 1, 2022. To describe the characteristics of SARS-CoV-2 illness following a third vaccination, we selected cases and controls who had received a third and second dose of monovalent vaccination against COVID-19, respectively, and reported a first positive SARS-CoV-2 test at least 7 days after most recent vaccination. Cases and controls were matched (1:1) based on age, sex, BMI, time between first vaccination and infection, and week of testing. We used logistic regression models (adjusted for age, sex, BMI, level of social deprivation and frailty) to analyse associations of disease severity, overall disease duration, and individual symptoms with booster vaccination status. To assess for potential waning of vaccine effectiveness, we compared disease severity, duration, and symptom profiles of individuals testing positive within 3 months of most recent vaccination (reference group) to profiles of individuals infected between 3 and 4, 4–5, and 5–6 months, for both third and second dose. All analyses were stratified by time period, based on the predominant SARS-CoV-2 variant at time of infection (Delta: June 1, 2021–27 Nov, 2021; Omicron: 20 Dec, 2021-Apr 1, 2022). During the study period, 50,162 (Delta period) and 162,041 (Omicron) participants reported a positive SARS-CoV-2 test. During the Delta period, infection following three vaccination doses was associated with lower odds of long COVID (symptoms≥ 4 weeks) (OR=0.83, CI[0.50–1.36], p < 0.0001), hospitalisation (OR=0.55, CI[0.39–0.75], p < 0.0001) and severe symptoms (OR=0.36, CI[0.27–0.49], p < 0.0001), and higher odds of asymptomatic infection (OR=3.45, CI[2.86–4.16], p < 0.0001), compared to infection following only two vaccination doses. During the Omicron period, infection following three vaccination doses was associated with lower odds of severe symptoms (OR=0.48, CI[0.42–0.55], p < 0.0001). During the Delta period, infected individuals were less likely to report almost all individual symptoms after a third vaccination. During the Omicron period, individuals were less likely to report most symptoms after a third vaccination, except for upper respiratory symptoms e.g. sneezing (OR=1.40, CI[1.18–1.35], p < 0.0001), runny nose (OR=1.26, CI[1.18–1.35], p < 0.0001), sore throat (OR=1.17, CI[1.10–1.25], p < 0.0001), and hoarse voice (OR=1.13, CI[1.06–1.21], p < 0.0001), which were more likely to be reported. There was evidence of reduced vaccine effectiveness during both Delta and Omicron periods in those infected more than 3 months after their most recent vaccination, with increased reporting of severe symptoms, long duration illness, and most individual symptoms. This study suggests that a third dose of monovalent vaccine may reduce symptoms, severity and duration of SARS-CoV-2 infection following vaccination. For Omicron variants, the third vaccination appears to reduce overall symptom burden but may increase upper respiratory symptoms, potentially due to immunological priming. There is evidence of waning vaccine effectiveness against progression to symptomatic and severe disease and long COVID after three months. Our findings support ongoing booster vaccination promotion amongst individuals at high risk from COVID-19, to reduce severe symptoms and duration of illness, and health system burden. Disseminating knowledge on expected symptoms following booster vaccination may encourage vaccine uptake. • This prospective case-control study used data from over 200,000 community-based participants. • A third monovalent vaccine dose reduced symptoms, severity and duration of SARS-CoV-2 infection post-vaccination. • There was waning of vaccine effectiveness against progression to symptomatic disease over time. • Findings support ongoing booster vaccination promotion for individuals at high risk from COVID-19. [ABSTRACT FROM AUTHOR]

Despite recommendations for COVID-19 primary series completion and booster doses for children and adolescents, coverage has been less than optimal, particularly in some subpopulations. This study explored disparities in childhood/adolescent COVID-19 vaccination, parental intent to vaccinate their children and adolescents, and reasons for non-vaccination in the US. Using the U.S. Census Bureau's Household Pulse Survey (HPS), we analyzed households with children aged <18 years using data collected from September 14 to November 14, 2022 (n = 44,929). Child and adolescent COVID-19 vaccination coverage (≥1 dose, completed primary series, and booster vaccination) and parental intentions toward vaccination were assessed by sociodemographic characteristics. Factors associated with child and adolescent vaccination coverage were examined using multivariable regression models. Reasons for non-vaccination were assessed overall, by the child's age group and respondent's age group. Overall, approximately half (50.1%) of children aged < 18 years were vaccinated against COVID-19 (≥1 dose). Completed primary series vaccination was 44.2% among all children aged <18 years. By age group, completed primary series was 13.2% among children <5 years, 43.9% among children 5–11 years, and 63.3% among adolescents 12–17 years. Booster vaccination among those who completed the primary series was 39.1% among children 5–11 years and 55.3% among adolescents 12–17 years. Vaccination coverage differed by race/ethnicity, educational attainment, household income, region, parental COVID-19 vaccination status, prior COVID-19 diagnosis, child's age group, and parental age group. Parental reluctance was highest for children aged <5 years (46.8%). Main reasons for non-vaccination among reluctant parents were concerns about side effects (53.3%), lack of trust in COVID-19 vaccines (48.7%), and the belief that children do not need a COVID-19 vaccine (38.8%). Disparities in COVID-19 vaccination coverage among children and adolescents continue to exist. Further efforts are needed to increase COVID-19 primary series and booster vaccination and parental confidence in vaccines. Using survey data collected from September 14 to November 14, 2022, COVID-19 vaccination coverage was low among children and adolescents. Overall, approximately half (50.1%) of the children aged <18 years were vaccinated against COVID-19 (≥1 dose). Completed primary series vaccination was 44.2% among all children aged < 18 years. By age group, completed primary series was 13.2% among children <5 years, 43.9% among children 5–11 years, and 63.3% among adolescents 12–17 years. Booster vaccination, among those who completed the primary series, was 39.1% among children 5–11 years and 55.3% among adolescents 12–17 years. Vaccination coverage differed by race/ethnicity, educational attainment, household income, region, parental COVID-19 vaccination status, prior COVID-19 diagnosis, child's age group, and parental age group. Parental reluctance was the highest for children aged <5 years (46.8%), followed by children 5–11 years (35.8%) and adolescents 12–17 years (23.5%). Main reasons for non-vaccination among reluctant parents were concerns about side effects (53.3%), lack of trust in COVID-19 vaccines (48.7%), the belief that children do not need a COVID-19 vaccine (38.8%), lack of trust in the government (35.6%), and that children in the household were not members of a high-risk group (32.8%). Disparities in COVID-19 vaccination coverage among children and adolescents continue to exist. Further efforts are needed to increase COVID-19 primary series and booster vaccination and parental confidence in vaccines. [ABSTRACT FROM AUTHOR]

The recently mutated severe acute respiratory syndrome coronavirus 2 variant Omicron has very high infectivity and a strong ability to evolve and evade immunity. We collected six sets of sera from uninfected individuals and individuals recovering from breakthrough infections who completed homologous or heterologous booster immunization and assessed their susceptibility against the BA.5.2.48, BF.7.14, XBB.1.5, XBB.1.5.4, and XBB.1.16 subvariants. The results demonstrated that the Omicron variants possess an exceptional potential to evade the immune barriers strengthened by vaccine administration and natural infections in the population, particularly XBB.1.16, and showed that heterologous boosters exhibit higher vaccine efficacy compared with homologous boosters. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines based on variant strains have been in use as booster doses to update immunity against circulating variants. Here we present the results of a phase one prospective, randomized, and open-labeled trial to study the safety and immunogenicity of a booster dose consisting of a subunit vaccine based on the stabilized prefusion SARS-CoV-2 spike protein, MVC-COV1901, or its Beta version, MVC-COV1901-Beta. Participants aged ≥18 and <55 years who received two or three prior doses of MVC-COV1901 vaccines were enrolled and were to receive a booster dose of either 15 mcg of MVC-COV1901, 15 mcg, or 25 mcg of MVC-COV1901-Beta in a 1:1:1 ratio. Adverse reactions after either MVC-COV1901 or MVC-COV1901-Beta booster doses after two or three doses of MVC-COV1901 were comparable and mostly mild and transient. At four weeks after the booster dose, participants with two prior doses of MVC-COV1901 had higher levels of neutralizing antibodies against ancestral SARS-CoV-2, Beta, and Omicron variants than participants with three prior doses of MVC-COV1901, regardless of the type of booster used. MVC-COV1901 and MVC-COV1901-Beta can both be effectively used as booster doses against SARS-CoV-2, including the BA.4/BA.5 Omicron variants. [ABSTRACT FROM AUTHOR]

PurposePrevious studies have demonstrated that the majority of patients with an inborn error of immunity (IEI) develop a spike (S)-specific IgG antibody and T-cell response after two doses of the mRNA-1273 COVID-19 vaccine, but little is known about the response to a booster vaccination. We studied the immune responses 8 weeks after booster vaccination with mRNA-based COVID-19 vaccines in 171 IEI patients. Moreover, we evaluated the clinical outcomes in these patients one year after the start of the Dutch COVID-19 vaccination campaign.MethodsThis study was embedded in a large prospective multicenter study investigating the immunogenicity of COVID-19 mRNA-based vaccines in IEI (VACOPID study). Blood samples were taken from 244 participants 8 weeks after booster vaccination. These participants included 171 IEI patients (X-linked agammaglobulinemia (XLA;N=11), combined immunodeficiency (CID;N=4), common variable immunodeficiency (CVID;N=45), isolated or undefined antibody deficiencies (N=108) and phagocyte defects (N=3)) and 73 controls. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T-cell responses were evaluated. One year after the start of the COVID-19 vaccination program, 334 study participants (239 IEI patients and 95 controls) completed a questionnaire to supplement their clinical data focusing on SARS-CoV-2 infections.ResultsAfter booster vaccination, S-specific IgG titers increased in all COVID-19 naive IEI cohorts and controls, when compared to titers at 6 months after the priming regimen. The fold-increases did not differ between controls and IEI cohorts. SARS-CoV-2-specific T-cell responses also increased equally in all cohorts after booster vaccination compared to 6 months after the priming regimen. Most SARS-CoV-2 infections during the study period occurred in the period when the Omicron variant had become dominant. The clinical course of these infections was mild, although IEI patients experienced more frequent fever and dyspnea compared to controls and their symptoms persisted longer.ConclusionOur study demonstrates that mRNA-based booster vaccination induces robust recall of memory B-cell and T-cell responses in most IEI patients. One-year clinical follow-up demonstrated that SARS-CoV-2 infections in IEI patients were mild. Given our results, we support booster campaigns with newer variant-specific COVID-19 booster vaccines to IEI patients with milder phenotypes.

Throughout the COVID-19 pandemic, changes in policy, shifts in behavior, and the emergence of new SARS-CoV-2 variants spurred multiple waves of transmission. Accurate assessments of the changing risks were vital for ensuring adequate healthcare capacity, designing mitigation strategies, and communicating effectively with the public. Here, we introduce a model of COVID-19 transmission and vaccination that provided rapid and reliable projections as the BA.1, BA.4 and BA.5 variants emerged and spread across the US. For example, our three-week ahead national projection of the early 2021 peak in COVID-19 hospitalizations was only one day later and 11.6–13.3% higher than the actual peak, while our projected peak in mortality was two days earlier and 0.22–4.7% higher than reported. We track population-level immunity from prior infections and vaccination in terms of the percent reduction in overall susceptibility relative to a completely naive population. As of October 1, 2022, we estimate that the US population had a 36.52% reduction in overall susceptibility to the BA.4/BA.5 variants, with 61.8%, 15.06%, and 23.54% of immunity attributable to infections, primary series vaccination, and booster vaccination, respectively. We retrospectively projected the potential impact of expanding booster coverage starting on July 15, 2022, and found that a five-fold increase in weekly boosting rates would have resulted in 70% of people over 65 vaccinated by Oct 10, 2022 and averted 25,000 (95% CI: 14,400–35,700) deaths during the BA.4/BA.5 surge. Our model provides coherent variables for tracking population-level immunity in the increasingly complex landscape of variants and vaccines and enables robust simulations of plausible scenarios for the emergence and mitigation of novel COVID variants.

Abstract Introduction Effect of booster vaccination and vitamin D status on antibody production of Omicron variant‐infected adults need to be further explored. Methods A retrospective, longitudinal, real‐world cohort study was performed. All included cases were divided into vitamin D deficiency (VDD) and non‐VDD (control) groups according to baseline serum 25‐hydroxyvitamin D [25(OH)D] concentration and then into unvaccinated, routinely vaccinated, and booster vaccinated VDD and control subgroups according to vaccination status. Antibody dynamics were observed within six time periods during hospitalization. Results A total of 204 adult cases were included, of which 121 (59%) were males; 23 (11%), 31 (15%), and 26 (13%) or 50 (25%), 35 (17%), and 39 (19%) were unvaccinated, routinely vaccinated, and booster vaccinated VDD cases or controls, respectively. The median (interquartile range) for age and baseline 25(OH)D concentration was 42.5 (31–53.5) years and 21.5 (18–25.4) ng/mL, respectively. The IgM titers within 3 to 7 days and 7 to 14 days increased rapidly to 1.8‐fold (P

Early studies have found that the initial COVID-19 vaccination series was protective against severe symptoms and long COVID. However, few studies have explored the association of booster doses on severe disease outcomes and long COVID. This cross-sectional analysis used data from the 2022 US National Health Interview Survey data to investigate how vaccination status correlates with COVID-19 infection severity and long COVID among previously infected individuals. Participants were categorized into three groups: those who had received at least one booster, those with only the initial complete vaccination series, and those with either an incomplete series or no vaccinations. Out of 9521 survey respondents who reported a past positive COVID-19 test, 51.2% experienced moderate/severe infections, and 17.6% experienced long COVID. Multivariable regression models revealed that receiving at least one booster shot was associated with lower odds of experiencing moderate/severe symptoms (aOR = 0.78, p < 0.001) compared to those unvaccinated or with an incomplete series. Additionally, having at least one booster reduced long COVID odds by 24% (aOR = 0.76, p = 0.003). Completing only the primary vaccine series did not significantly decrease the likelihood of severe illness or long COVID. These findings support the continued promotion of booster vaccinations to mitigate long COVID risks in vulnerable populations.

Abstract Background SARS-CoV-2 breakthrough infections (BI) after vaccine booster dose are a relevant public health issue. Methods Multicentric longitudinal cohort study within the ORCHESTRA project, involving 63,516 health workers (HW) from 14 European settings. The study investigated the cumulative incidence of SARS-CoV-2 BI after booster dose and its correlation with age, sex, job title, previous infection, and time since third dose. Results 13,093 (20.6%) BI were observed. The cumulative incidence of BI was higher in women and in HW aged 130 days. Conclusions The risk of BI after booster is significantly reduced by previous infection, heterologous vaccination, and older ages. Immunosuppression is relevant for increased BI incidence. Time elapsed from booster affects BI severity, confirming the public health usefulness of booster. Further research should focus on BI trend after 4th dose and its relationship with time variables across the epidemics.

Abstract Background Negative conversion of nucleic acid was a key factor in deciding discharge or the end of isolation of asymptomatic or mild COVID-19 patients. We aimed to explore the effect of vaccination on the time to negative conversion after Omicron infection. Methods This retrospective cohort study included asymptomatic or mild patients with COVID-19 admitted to Fangcang shelter Hospital from November 10, 2022 to December 2, 2022. The relationship between vaccination status and the time to negative conversion was analyzed by multiple linear regression. Results A total of 2,104 asymptomatic or mild COVID-19 patients were included in the analysis, of whom 1,963 were vaccinated. The mean time to negative conversion of no vaccination, one dose, two doses, and three doses were 12.57 (5.05), 12.18 (3.46), 11.67 (4.86) and 11.22 (4.02) days, respectively (p = 0.002). Compared with no vaccination, two doses (β=-0.88, 95% CI: -1.74, -0.02, p = 0.045), and three doses (β=-1.51, 95% CI: -2.33, -0.70, p

Objective: To further explore the effect of vaccination regimen and frequency on clinical outcomes of breakthrough infections caused by the Omicron variant, as well as the durability of vaccine effectiveness. Methods: A retrospective, propensity score matching, real-world cohort study was conducted. Vaccination frequency was categorized into regular vaccination, first booster, and second booster. Results: A total of 7428 cases were included, with 3910 (53 %) being male. The median age was 39 years. BA.2 than BA.5/5.2 infection presented with more pulmonary symptoms and fewer influenza-like symptoms. Among the 3516 cases of BA.5/5.2 breakthrough infections, patients who received the second booster than the first booster or regular vaccination had higher first IgM and IgG titers and first cycle thredhold values for N gene on admission, a lower percentage of fever, lower peak body temperatures, and a higher percentage of asymptomatic cases. Patients who received the first booster vaccinated with homologous mRNA or heterologous inactivated plus mRNA vaccines than homologous inactivated vaccines had higher first IgM and IgG titers, a higher percentage of asymptomatic cases, and a lower percentage of fever. Moreover, significantly different first IgG titers were observed among patients receiving the second booster vaccinated with any of the three regimens. There was no statistical difference between booster regimens of homologous mRNA vaccines and heterologous inactivated plus mRNA vaccines. Patients in Month 7- than Month 0–6 after the first booster had lower first IgM and IgG titers and first cycle thredhold values, a lower percentage of asymptomatic cases, and a higher percentage of fever; and a higher percentage of pneumonia after the second booster. Conclusions: Repeated booster vaccinations every six months, with priority given to heterologous mRNA vaccine booster regimens in countries previously primarily using inactivated vaccines, may provide protection for adult patients with Omicron-variant breakthrough infections and improve clinical outcomes.

ABSTRACTCoronavirus disease 2019 (COVID-19) vaccines have saved millions of lives. However, variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged causing large numbers of breakthrough infections. These developments necessitated the rollout of COVID-19 vaccine booster doses. It has been reported that mucosal antibody levels in the upper respiratory tract, especially for secretory IgA (sIgA), correlate with protection from infection with SARS-CoV-2. However, it is still unclear how high levels of mucosal antibodies can be induced. In this study, we measured serum IgG, saliva IgG, and saliva sIgA responses in individuals who received COVID-19 mRNA booster vaccinations or who experienced breakthrough infections. We found that mRNA booster doses could induce robust serum and saliva IgG responses, especially in individuals who had not experienced infections before, but saliva sIgA responses were weak. In contrast, breakthrough infections in individuals who had received the primary mRNA vaccination series induced robust serum and saliva IgG as well as saliva sIgA responses. Individuals who had received a booster dose and then had a breakthrough infection showed low IgG induction in serum and saliva but still responded with robust saliva sIgA induction. These data suggest that upper respiratory tract exposure to antigen is an efficient way of inducing mucosal sIgA while exposure via intramuscular injection is not.IMPORTANCEAntibodies on mucosal surfaces of the upper respiratory tract have been shown to be important for protection from infection with SARS-CoV-2. Here we investigate the induction of serum IgG, saliva IgG, and saliva sIgA after COVID-19 mRNA booster vaccination or breakthrough infections.

Introduction: The mortality rate of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTR) has significantly decreased with the implementation of vaccination programs. However, the real-world information on the impact of vaccinations, particularly in resource limited settings in Asia, is still limited. Methods: The Thai Transplant Society conducted a prospective multicenter cohort registry, including KTR diagnosed with COVID-19. Cox proportional hazards regression was used to examine factors associated with poor COVID-19 outcomes and complications, including death, COVID-19 pneumonia, and superimposed bacterial infection. Results: A total of 413 patients from 17 transplant centers who developed COVID-19 were analyzed. The COVID-19 mortality rate was 5.6 % and the incidence of pneumonia was 18.8 %. With each 10-year increase in age, the risk of death, pneumonia, and bacterial infection increased by 61 %, 32 %, and 43 %, respectively. A total of 11.4 % of KTR received one dose of COVID vaccination (incomplete vaccination), 25.7 % received two doses (complete primary vaccination), 42.6 % received three doses (first booster dose), and 10.4 % received four doses of vaccination (second booster dose). Even a single dose of vaccination significantly decreased the risk of death, pneumonia, and superimposed bacterial infection among KTR compared to those who remained unvaccinated. Completing the primary vaccination (2-dose) reduced the risk of death by 89 %, pneumonia by 88 %, and bacterial infection by 83 % compared to unvaccinated KTR. Receiving a booster dose (third or fourth dose) further reduced the risk of death by 94 %, pneumonia by 95 %, and bacterial infection by 96 % compared to unvaccinated individuals. Conclusions: This Asian cohort demonstrated that the mortality and complications of COVID-19 significantly decreased in KTR after the national immunization. Our study suggests that any type of COVID-19 vaccine can be beneficial in preventing adverse outcomes. Administering booster vaccinations is strongly recommended.

Diphtheria is an infectious disease caused by a strain of Corynebacterium diphtheria and forms part of the childhood vaccine-preventable diseases. The Diphtheria vaccine is a component of one of the routine vaccines given to children thrice before their first birthday. The protection against diphtheria derived from the diphtheria vaccine in infancy wanes in later childhood, necessitating a booster dose to protect the child as they grow older. To determine the impact of a booster dose of the diphtheria vaccine amidst a contaminated environment, a diphtheria model that incorporates a vaccine booster and a contaminated environment is formulated. The reproduction number R0 is computed and used to prove the local and global stability of the disease-free equilibrium. Global sensitivity analysis is conducted via the application of Latin Hypercube Sampling (LHS) with a Partial Rank Correlation coefficient on the infected humans and the contaminated environment to deduce the most sensitive parameters of the dynamics of diphtheria disease. Then, the model is further extended based on the result of the global sensitivity analysis by introducing four time-dependent controls, disinfection, screening/treatment, booster vaccination, and hygiene practice, to form an optimal control model. The control model is analyzed using Pontryagin’s maximum principle. The numerical simulation shows that diphtheria disease will reduce drastically in the community if any control combination involves booster vaccination since the diphtheria vaccine in infancy wanes after ten years. In a situation where there are limited resources to implement all the controls simultaneously, it is recommended to implement any two of the combined controls: disinfection of the environment and administration of booster vaccination or screening/treatment of the asymptomatic infected and administration of booster vaccination. The study shows that the best combination is to disinfect the environment, screen/treat the asymptomatic infected humans, and administer booster vaccination to the community.