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Background: The current study analyzed articles shared on Facebook between 2019 and 2021 that discuss the HPV vaccine. Results address a gap in knowledge about the persuasive strategies used in HPV vaccine discourse on Facebook. Methods: Using Buzzsumo.com, we collected 138 articles, shared on Facebook between 2019 and 2021, with the highest "engagement scores," or total number of reactions, comments, and shares. Using a content analysis methodology, three independent coders were trained in using the study codebook, achieved acceptable inter-rater reliability (Krippendorf's alpha = 0.811), and coded each article in Atlas.ti. Results: Seventy-two articles had a positive valence toward the HPV vaccine, 48 had a negative valence, and 18 were mixed-valence or neutral. Pro-vaccine articles presented a variety of evidence types in support of benefits of HPV vaccination. Pro-vaccine articles primarily originated from national and local news sources. Anti-vaccine articles combined presentation of evidence with persuasive arguments and strategies, such as mistrust of institutions, fear appeals, ideological appeals, presenting a high number of arguments or detail, and minimizing the severity of HPV. Three sources were responsible for producing 62.5% of all anti-vaccine articles in the dataset. Mixed-valence or neutral articles mixed cancer prevention discourse with ideological appeals about protecting parental rights, and were mostly produced by local news outlets. Conclusion: The results of this study can help health communicators anticipate the types of discourses that vaccine-hesitant parents may have encountered online. Implications and suggestions for practice are discussed. [ABSTRACT FROM AUTHOR]

Background: To combat coronavirus disease 2019 (COVID-19), booster vaccination strategies are important. However, the optimal administration of booster vaccine platforms remains unclear. Herein, we aimed to assess the benefits and harms of three or four heterologous versus homologous booster regimens. Methods: From November 3 2022 to December 21, 2023, we searched five databases for randomised clinical trials (RCT). Reviewers screened, extracted data, and assessed bias risks independently with the Cochrane risk-of-bias 2 tool. We conducted meta-analyses and trial sequential analyses (TSA) on our primary (all-cause mortality; laboratory confirmed symptomatic and severe COVID-19; serious adverse events [SAE]) and secondary outcomes (quality of life [QoL]; adverse events [AE] considered non-serious). We assessed the evidence with the GRADE approach. Subgroup analyses were stratified for trials before and after 2023, three or four boosters, immunocompromised status, follow-up, risk of bias, heterologous booster vaccine platforms, and valency of booster. Results: We included 29 RCTs with 43 comparisons (12,538 participants). Heterologous booster regimens may not reduce the relative risk (RR) of all-cause mortality (11 trials; RR 0.86; 95% CI 0.33 to 2.26; I2 0%; very low certainty evidence); laboratory-confirmed symptomatic COVID-19 (14 trials; RR 0.95; 95% CI 0.72 to 1.25; I2 0%; very low certainty); or severe COVID-19 (10 trials; RR 0.51; 95% CI 0.20 to 1.33; I2 0%; very low certainty). For safety outcomes, heterologous booster regimens may have no effect on SAE (27 trials; RR 1.15; 95% CI 0.68 to 1.95; I2 0%; very low certainty) but may raise AE considered non-serious (20 trials; RR 1.19; 95% CI 1.08 to 1.32; I2 64.4%; very low certainty). No data on QoL was available. Our TSAs showed that the cumulative Z curves did not reach futility for any outcome. Conclusions: With our current sample sizes, we were not able to infer differences of effects for any outcomes, but heterologous booster regimens seem to cause more non-serious AE. Furthermore, more robust data are instrumental to update this review. [ABSTRACT FROM AUTHOR]

Background: The magnitude and durability of cell-mediated immunity in older and severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether vaccination induces an anti-inflammatory cellular immune response. To address these issues, a 48-week-long prospective longitudinal study was conducted. A total of 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients [median age; 72.0 years], and 21 healthcare workers [median age; 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for the assessment of spike-specific PBMC responses before primary vaccination, 24 weeks after primary vaccination, and three months after booster vaccination. Cellular immune responses to severe acute respiratory syndrome coronavirus 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, and IL-10 levels secreted from the spike protein peptide-stimulated PBMCs of participants. Results: LTCF residents exhibited significantly lower IFN-γ, TNF, IL-2, and IL-6 levels than healthcare workers after the primary vaccination. Booster vaccination increased IL-2 and IL-6 levels in LTCF residents comparable to those in healthcare workers, whereas IFN-γ and TNF levels in LTCF residents remained significantly lower than those in healthcare workers. IL-10 levels were not significantly different from the initial values after primary vaccination but increased significantly after booster vaccination in all subgroups. Multivariate analysis showed that age was negatively associated with IFN-γ, TNF, IL-2, and IL-6 levels but not with IL-10 levels. The levels of pro-inflammatory cytokines, including IFN-γ, TNF, IL-2, and IL-6, were positively correlated with humoral immune responses, whereas IL-10 levels were not. Conclusions: Older and severely frail individuals may exhibit diminished spike-specific PBMC responses following COVID-19 vaccination compared to the general population. A single booster vaccination may not adequately enhance cell-mediated immunity in older and severely frail individuals to a level comparable to that in the general population. Furthermore, booster vaccination may induce not only a pro-inflammatory cellular immune response but also an anti-inflammatory cellular immune response, potentially mitigating detrimental hyperinflammation. [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]

Background: With the onset of the COVID-19 pandemic, governments implemented social distancing regulations to limit the spread of the disease. Some health experts warned that these measures could negatively affect access to essential health services, such as routine childhood immunizations. Others noted that without these regulations, COVID-19 cases would increase, leading to overburdened health systems. Methods: We analyze four years (2018–2021) of monthly administrative data on childhood immunizations in all administrative districts in Ghana and exploit variations in social distancing regulations across districts. Given variations in social distancing regulations across Ghanaian districts, we can further differentiate between the effect of public lockdowns and the effect of the pandemic. Results: We find that child immunizations in Ghana declined by 6% during the public lockdown in April 2020, but the country compensated with higher vaccination rates starting in June, and immunization services recovered to pre-pandemic growth levels by 2021. Time-critical vaccines, such as polio, were not affected at all. We do find a substantially larger disruption in April 2020 (14%) and a slower recovery in 2020 in the 40 lockdown-affected districts. Interestingly, vaccination rates already decreased in February and March by about 5% before the public lockdown and before the pandemic had reached Ghana, but with the pandemic already spreading globally and in the news. Conclusion: Our results indicate that the negative effect on child immunization was less severe and shorter than predicted by experts. Fear of COVID-19 and delayed vaccination campaigns had a substantial impact on childhood immunization while rising COVID-19 cases and moderate social distancing regulations did not seem to affect immunization rates. [ABSTRACT FROM AUTHOR]

Background: Oncogenic types of human Papillomavirus (HPV) infection cause substantial morbidity and mortality in Nigeria. Nigeria has low cervical cancer screening and vaccination rates, suggesting the need for community engagement to enhance reach and uptake. We organised a designathon to identify community-led, innovative approaches to promote HPV screening and vaccination for women and girls, respectively, in Nigeria. A designathon is a three-phase participatory process informed by design thinking that includes the preparation phase that includes soliciting innovative ideas from end-users, an intensive collaborative event to co-create intervention components, and follow-up activities. Methods: We organised a three-phase designathon for women (30-65yrs) and girls (11-26yrs) in Nigeria. First, we launched a national crowdsourcing open call for ideas on community-driven strategies to support HPV screening among women and vaccination among girls. The open call was promoted widely on social media and at in-person gatherings. All eligible entries were graded by judges and 16 exceptional teams (with 4-6members each). All six geo-political zones of Nigeria were invited to join an in-person event held over three days in Lagos to refine their ideas and present them to a panel of expert judges. The ideas from teams were reviewed and scored based on relevance, feasibility, innovation, potential impact, and mother-daughter team dynamics. We present quantitative data on people who submitted and themes from the textual submissions. Results: We received a total of 612 submissions to the open call from mother-daughter dyads. Participants submitted ideas via a website designated for the contest (n = 392), in-person (n = 99), email (n = 31), or via an instant messaging application (n = 92). Overall, 470 were eligible for judging after initial screening. The average age of participants for daughters was 19 years and 39 years for mothers. Themes from the top 16 proposals included leveraging local leaders (5/16), faith-based networks (4/16), educational systems (4/16), and other community networks (7/16) to promote awareness of cervical cancer prevention services. After an in-person collaborative event, eight teams were selected to join an innovation training boot camp, for capacity building to implement ideas. Conclusions: Innovative strategies are needed to promote HPV screening for mothers and vaccination for girls in Nigeria. Our designathon was able to facilitate Nigerian mother-daughter teams to develop cervical cancer prevention strategies. Implementation research is needed to assess the effectiveness of these strategies. [ABSTRACT FROM AUTHOR]

Background: Despite the availability of effective vaccines, human papillomavirus (HPV) vaccine uptake remains low in most resource-limited settings including Nigeria. Mobile health technology (mHealth) has the potential to empower patients to manage their health, reduce health disparities, and enhance the uptake of HPV vaccination. Aim: The "mHealth-HPVac" study will assess the effects of mHealth using short text messages on the uptake of HPV vaccination among mothers of unvaccinated girls aged 9–14 years and also determine the factors influencing the uptake of HPV vaccination among these mothers. Methods: This protocol highlights a randomised controlled trial involving women aged 25–65 years who will be enrolled on attendance for routine care at the General Outpatient clinics of Lagos University Teaching Hospital, Lagos, Nigeria between July and December 2024. At baseline, n = 123 women will be randomised to either a short text message or usual care (control) arm. The primary outcome is vaccination of the participant's school-age girl(s) at any time during the 6 months of follow-up. The associations between any two groups of continuous variables will be assessed using the independent sample t-test for normally distributed data, or the Mann-Whitney U test for skewed data. For two groups of categorical variables, the Chi-square (X2) test or Fisher's exact test will be used, as appropriate. Using the multivariable binary logistic regression model, we will examine the effects of all relevant sociodemographic and clinical variables on HPV vaccination uptake among mothers of unvaccinated but vaccine-eligible school-age girls. Statistical significance will be reported as P < 0.05. Discussion: The mHealth-Cervix study will evaluate the impact of mobile technologies on HPV vaccination uptake among mothers of unvaccinated but vaccine-eligible school-age girls in Lagos, Nigeria as a way of contributing to the reduction in the wide disparities in cervical cancer incidence through primary prevention facilitated using health promotion to improve HPV vaccination uptake. Registration: PACTR202406727470443 (6th June 2024). [ABSTRACT FROM AUTHOR]

Background: For the past three years, the pandemic has had a major effect on global public health, mainly on those with underlying medical conditions, such as people living with Multiple Sclerosis. Vaccination among this group is of great importance, and the long-term impacts of vaccination and its safety on the health of these patients will continue to be revealed. Therefore, risks related to vaccination and immune response need to be assessed. The objective here was to characterize the immune response, short-term safety, and the effects of multiple variables on these factors after COVID-19 vaccination (mainly Sinopharm) among people with Multiple Sclerosis. We assessed the short-term safety and humoral SARS-COV-2 anti-RBD IgG response using a data collection form and Immunoassay, respectively. Results: No severe adverse events or MS relapse was observed. Myalgia/body pain (26.7%), low-grade fever (22.2%), and mild headache (15.6%) were the most common adverse events. The use and type of vaccine influenced the frequency of side effects with a p-value < 0.0001. Regarding immune response, patients on rituximab and fingolimod had a lower antibody titer compared to other medications. With a significant difference, hybrid immunity (p-value: 0.047) and type of DMTs (p-value: 0.017) affected the humoral response. Conclusion: There is a low incidence of serious adverse effects, MS worsening or relapse after COVID-19 vaccination, and mainly, side effects are similar to that of the general population. It appears that treatment with various disease-modifying therapies does not induce or worsen the post-vaccination side effects, although some, including Rituximab and fingolimod, may affect the immunity induced after vaccination. [ABSTRACT FROM AUTHOR]

Background: Understanding the relative contributions of SARS-CoV-2 infection-induced and vaccine-induced seroprevalence is key to measuring overall population-level seroprevalence and help guide policy decisions. Methods: Using a series of six population-based cross-sectional surveys conducted among persons aged ≥7 years in a large health system with over 4.5 million members between May 2021 and April 2022, we combined data from the electronic health record (EHR), an electronic survey and SARS-CoV-2 spike antibody binding assay, to assess the relative contributions of infection and vaccination to population-level SARS-CoV-2 seroprevalence. EHR and survey data were incorporated to determine spike antibody positivity due to SARS-CoV-2 infection and COVID-19 vaccination. We used sampling and non-response weighting to create population-level estimates. Results: We enrolled 4,319 persons over six recruitment waves. SARS-CoV-2 spike antibody seroprevalence increased from 83.3% (CI 77.0–88.9) in May 2021 to 93.5% (CI 89.5–97.5) in April 2022. By April 2022, 68.5% (CI 61.9–74.3) of the population was seropositive from COVID-19 vaccination only, 13.9% (10.7–17.9) from COVID-19 vaccination and prior diagnosed SARS-CoV-2 infection, 8.2% (CI 4.5–14.5) from prior diagnosed SARS-CoV-2 infection only and 2.9% (CI 1.1–7.6) from prior undiagnosed SARS-CoV-2 infection only. We found high agreement (≥97%) between EHR and survey data for ascertaining COVID-19 vaccination and SARS-CoV-2 infection status. Conclusions: By April 2022, 93.5% of persons had detectable SARS-CoV-2 spike antibody, predominantly from COVID-19 vaccination. In this highly vaccinated population and over 18 months into the pandemic, SARS-CoV-2 infection without COVID-19 vaccination was a small contributor to overall population-level seroprevalence. [ABSTRACT FROM AUTHOR]

The cancer vaccine is one of the potent cancer immunotherapies based on provoking antigen‐specific adaptive immune responses in patients. Activating host antigen‐presenting cells by delivering antigens and adjuvants is one of the most important requirements to enhance cancer vaccine efficacy. This study proposes an effective cancer vaccine platform based on injectable mesocellular foam (MCF) silica microparticles with a dual role capable of in situ recruitment of host dendritic cells (DCs) and intracellular delivery of antigens to the recruited DCs. Subcutaneously administrated MCF microparticles loaded with chemoattractant to DCs (GM‐CSF), antigenic protein (OVA), and TLR9 agonist (CpG‐ODN) lead to robust DC maturation and high antigen‐specific T cell responses. The cell recruitment, DC activation, and T cell responses of MCF‐based cancer vaccine are significantly higher than injectable mesoporous silica scaffold, of which role is mostly limited to the cell recruiting scaffold. These features of MCF lead to effective inhibition of tumor growth in prophylactic vaccine setting and lung metastatic cancer model, representing MCF enabling cell‐recruiting scaffold formation and intracellular delivery of antigen can be a promising material platform for an enhanced cancer vaccine. [ABSTRACT FROM AUTHOR]

Introduction: Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. Methods: This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019–2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination for bivalent COVID-19 and influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants' experiences with AEs also were collected for the COVID-19 vaccine recipients. Results: Females were more likely to report local AEs after either influenza (OR = 2.28, p = 0.001) or COVID-19 (OR = 2.57, p = 0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after either influenza (OR = 1.18, p = 0.552) or COVID-19 (OR = 0.96, p = 0.907) vaccination. Hormonal birth control use did not impact the rates of reported AEs following influenza vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. Conclusions: Our findings highlight the need for sex- and gender-inclusive policies to inform more effective mandatory occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers, a predominately female population, and to more fully characterize the post-vaccination behavioral differences between men and women. Plain English summary: Research that addresses both the sex and gender differences of vaccine outcomes and behaviors is lacking. In this survey study of healthcare workers, comprised of mostly reproductive-aged females/women, we investigated biological sex (male/female) and gender (man/woman) differences in vaccine adverse events and outcomes following either influenza or bivalent COVID-19 vaccination. Regardless of age or race, females were more likely to report local (at injection site), but not systemic (whole body), adverse events than males, consistent across influenza and bivalent COVID-19 vaccine cohorts. Sex hormones are hypothesized to play a role in the differences in immune response following vaccination between males and females. We investigated if hormonal birth control use among females may be associated with differences in vaccine adverse events among the influenza vaccine cohort. However, there was no difference in the likelihood of reporting adverse events between birth control users and non-users. Based on open-ended responses to survey questions, women were found to report more interruptions to their daily routine than men following COVID-19 vaccination. Women were also more likely to seek out self-treatment with over-the-counter medication and intentionally schedule their vaccination around days off in anticipation of adverse events. With nearly 80% of healthcare jobs held by women, even higher for direct patient care positions like nursing, females/women may be disproportionately impacted by mandated annual vaccinations. Vaccinations are necessary for the prevention of disease transmission; however, our findings highlight a need for more equitable occupational vaccine strategies that consider both sex and gender differences. Highlights: • Research that addresses both the sex and gender disparities of vaccine outcomes and behaviors is lacking. • This active reporting study implements both logistic regression and thematic analyses to examine sex and gender differences in AEs following influenza or bivalent COVID-19 vaccination among a cohort of predominately female, reproductive-aged healthcare workers. • Females report more local adverse events than males following either influenza or bivalent COVID-19 vaccination, regardless of age or race. • Women report more disruptions to their daily routines than men. Women also are more likely to seek out self-treatment and schedule their vaccinations around days off in anticipation of adverse events. • Sex and gender differences in vaccine AEs and outcomes should drive the development of more equitable vaccine strategies and policies in occupational health settings, particularly for mandated vaccinations. [ABSTRACT FROM AUTHOR]

Background: The exploration of cancer vaccines has yielded a multitude of studies, resulting in a diverse collection of information. The heterogeneity of cancer vaccine data significantly impedes effective integration and analysis. While CanVaxKB serves as a pioneering database for over 670 manually annotated cancer vaccines, it is important to distinguish that a database, on its own, does not offer the structured relationships and standardized definitions found in an ontology. Recognizing this, we expanded the Vaccine Ontology (VO) to include those cancer vaccines present in CanVaxKB that were not initially covered, enhancing VO's capacity to systematically define and interrelate cancer vaccines. Results: An ontology design pattern (ODP) was first developed and applied to semantically represent various cancer vaccines, capturing their associated entities and relations. By applying the ODP, we generated a cancer vaccine template in a tabular format and converted it into the RDF/OWL format for generation of cancer vaccine terms in the VO. '12MP vaccine' was used as an example of cancer vaccines to demonstrate the application of the ODP. VO also reuses reference ontology terms to represent entities such as cancer diseases and vaccine hosts. Description Logic (DL) and SPARQL query scripts were developed and used to query for cancer vaccines based on different vaccine's features and to demonstrate the versatility of the VO representation. Additionally, ontological modeling was applied to illustrate cancer vaccine related concepts and studies for in-depth cancer vaccine analysis. A cancer vaccine-specific VO view, referred to as "CVO," was generated, and it contains 928 classes including 704 cancer vaccines. The CVO OWL file is publicly available on: http://purl.obolibrary.org/obo/vo/cvo.owl, for sharing and applications. Conclusion: To facilitate the standardization, integration, and analysis of cancer vaccine data, we expanded the Vaccine Ontology (VO) to systematically model and represent cancer vaccines. We also developed a pipeline to automate the inclusion of cancer vaccines and associated terms in the VO. This not only enriches the data's standardization and integration, but also leverages ontological modeling to deepen the analysis of cancer vaccine information, maximizing benefits for researchers and clinicians. Availability: The VO-cancer GitHub website is: https://github.com/vaccineontology/VO/tree/master/CVO. [ABSTRACT FROM AUTHOR]

Background: The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically. Methods: Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China's National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed. Results: A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively. Conclusion: HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work. [ABSTRACT FROM AUTHOR]

Background: During the initial wave of the COVID-19 pandemic, there was a surprisingly low incidence of SARS-CoV-2 among People Who Use Drugs (PWUD) in Oslo, Norway, despite their heightened vulnerability regarding risk of infection and severe courses of the disease.This study aims to investigate the seroprevalence of SARS-CoV-2 antibodies among PWUD, their antibody responses to relevant virus infections and COVID-19 mRNA vaccines, and their vaccination coverage compared to the general population. Methods: Conducted as a prospective cohort study, data was collected from residents in six institutions for homeless PWUD and users of a low-threshold clinic for opioid agonist treatment. Ninety-seven participants were recruited for SARS-CoV-2 seroprevalence analysis. Additional two participants with known positive SARS-CoV-2 test results were recruited for further analyses. Twenty-five participants completed follow-up. Data included questionnaires, nasal swabs and blood samples. Data on vaccination coverage was obtained from the National Vaccine Register. Serologic methods included detection of antibodies to relevant virus proteins, neutralizing antibodies to SARS-CoV-2, antibodies to the full-length spike protein, and receptor-binding domain from SARS-CoV-2. Results: Among PWUD, antibodies to SARS-CoV-2 were detected in 2 out of 97 samples before vaccines against SARS-CoV-2 were available, comparable to a 2.8% frequency in population-based screening. Levels of serum antibodies to seasonal coronaviruses and Epstein-Barr-Virus (EBV) in PWUD were similar to population-based levels. After the second vaccine dose, binding and neutralizing antibody levels to SARS-CoV-2 in PWUD were comparable to controls. Eighty-four of PWUD received at least one dose of COVID-19 mRNA vaccine, compared to 89% in the general population. Conclusion: Results indicate that PWUD did not exhibit increased SARS-CoV-2 seroprevalence or elevated serum antibodies to seasonal coronaviruses and EBV. Moreover, vaccine responses in PWUD were comparable to controls, suggesting that vaccination is effective in conferring protection against SARS-CoV-2 also in this population. [ABSTRACT FROM AUTHOR]

Background: Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed. Methods: An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency. Results: Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8+ T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses. Conclusions: The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with "undruggability." Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses. The current investigation introduces an innovative conceptualization of bispecific short hairpin RNA (bs_shRNA) tailored for the equilibrated modulation of dual genes within a singular cellular context. This novel bs_shRNA was loaded into the genome of an oncolytic adenovirus to augment the therapeutic efficacy of oncolytic viral interventions via the targeted inhibition of mTOR and STAT3 pathways. In addition, the administration of BSV significantly reduced the volume of bladder cancer tumors, concomitantly facilitating an enhanced recruitment of CD8+T lymphocytes in vivo. [ABSTRACT FROM AUTHOR]

• Regardless of COVID-19 vaccine introduction to all countries in the WHO EMR in 2020–2021, there was inequity in access to vaccine and vaccination coverage across the region. • As of 31 December 2023, COVID-19 vaccine availability, vaccination coverage, and vaccine acceptance were improved in the region. • COVID-19 could imperil the high-risk groups, including healthcare workers and elderly. Due to low-risk perception on COVID-19, however, we recommend changing an approach from time-bound and project type approach to sustainable and long-term approach of COVID-19 vaccine delivery by integrating COVID-19 vaccination into EPI and PHC as a way-forward. In 2020–2021, all countries of the WHO Eastern Mediterranean Region [EMR] introduced COVID-19 vaccine with inequalities in coverage across countries. As for 2023, we reviewed subsequent progress in deployment, coverage, acceptance, and integration. As of 31 December 2023, coverage in EMR reached 51% for primary series and 19 % for the first booster, higher in high income countries (77 % and 44 %, respectively) than in upper middle-income countries (49 % and 20 %), Advance Market Commitment [AMC] non-Gavi eligible countries (47 % and 15 %) and AMC Gavi eligible countries (49 % and 16 %). Thirteen countries measured coverage among healthcare workers (76 % and 43 %, respectively) and 15 among elderly (69 % and 38 %, respectively). Three rounds of the regional Knowledge, Attitudes, and Practices [KAP] survey on COVID-19 vaccine acceptance in 2021–2022 indicated that acceptance increased from 20 % in June-July 2021 to 62 % in October-November 2021, and 77 % in June-July 2022. Those unvaccinated but intending to be vaccinated decreased from 60 % to 23 % and 11 %, respectively. Unvaccinated without intention to be vaccinated decreased from 15 % to 10 % and 11 %, respectively. Twenty out of 22 countries in the region had completely or partially integrated COVID-19 vaccination into the Expanded Programme on Immunization [EPI] and Primary Health Care [PHC]. Overall, challenges to reach high-risk groups persisted as the population was less concerned about Omicron variant of the SARS-CoV-2 virus. Countries should build on the trust, momentum, and lesson-learned generated from COVID-19 vaccination to get the highest risk groups vaccinated and switch from a time bound and project type approach to a sustainable and long-term approach for COVID-19 vaccine delivery that would be integrated into the routine EPI and PHC. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) poses a significant public health threat primarily caused by four major enteroviruses: enterovirus 71 (EV71), coxsackieviruses A16, A10, and A6. Broadly protective immune responses are essential for complete protection against these major enteroviruses. In this study, we designed a new tetravalent immunogen for HFMD, validated it in silico , in vivo evaluated the immunogenicity of the DNA-based tetravalent vaccine in mice, and identified immunogenic B-cell and T-cell epitopes. A new tetravalent immunogen, VP1me, was designed based on the chimeric protein and epitope-based vaccine principles. It contains a complete EV71 VP1 protein and six reported neutralizing B-cell epitopes derived from the four major enteroviruses causing HFMD. In silico validation using multiple immunoinformatic tools indicated good attributes of the VP1me immunogen suitable for vaccine development. The VP1me-based DNA vaccine efficiently induced both humoral and cellular immune responses in BALB/cAJcl mice. A combination of in silico prediction and immunoassays enabled the identification of immunogenic linear B-cell and CD8 T-cell epitopes within the VP1me immunogen. Immunodominant linear B-cell epitopes were identified in six regions of VP1me, with one epitope located at the N-terminus of the VP1 protein (aa 9–23) regarded as a novel epitope. Interestingly, some B-cell epitopes could also induce the CD8 T-cell response, suggesting their dual functions in immune stimulation. These results lay the groundwork for further development of VP1me as a new vaccine candidate. [ABSTRACT FROM AUTHOR]

• First study of ancestral recombinant vaccine, S-268019-b for prevention in Vietnam. • The vaccine efficacy for prevention not verified in Omicron-dominant period. • S-268019-b immunogenicity and tolerability confirmed. • Similar efficacy and safety of S-268019-b with other ancestral strain vaccines. Clinical trials of new vaccines based on existing variants of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are often impacted by the emergence of new virus variants. We evaluated the efficacy, immunogenicity, and safety of S-268019-b, a recombinant spike protein subunit vaccine based on the ancestral strain, for preventing symptomatic coronavirus disease 2019 (COVID-19) during the Omicron (BA.2)-dominant period in Vietnam. In this multicentre, phase 3, randomised (2:1), observer-blind, placebo-controlled crossover study, participants received 2 intramuscular doses (28 days apart) of either 10 µg of S-268019-b (Recombinant S-protein vaccine) or placebo. The primary endpoint was incidence of laboratory-confirmed symptomatic COVID-19 before crossover, with onset within 14 days following the second dose, in participants who were seronegative and reverse transcription polymerase chain reaction (RT-PCR)-negative at baseline. The secondary endpoints included immunogenicity and safety. In total, 8,594 participants were randomised (S-268019-b [n = 5,727]; placebo [n = 2,867]). Vaccine efficacy versus placebo was 39·1 % (95 % confidence interval [CI]:26·6–49·5; one-sided P = 0·0723). The incidence rate (95 % CI) of symptomatic COVID-19 was 776·41/1,000 person-years (682·04–880·19) in the S-268019-b group and 1272·87/1,000 person-years (1101·32–1463·57) in the placebo group. The geometric mean titres (95 % CI) of the SARS-CoV-2 neutralising antibody increased on Day 57 versus baseline with S-268019-b (34·66 [27·04–44·41] versus 2·50 (non-estimable) but not with placebo. There were no safety concerns regarding S-268019-b. S-268019-b did not demonstrate the targeted efficacy threshold against symptomatic COVID-19; however, findings were comparable with other prophylactic vaccines based on ancestor strain during the Omicron-dominant period. S-268019-b demonstrated immunogenicity and was well-tolerated. ClinicalTrials.gov identifier: NCT05212948. [ABSTRACT FROM AUTHOR]

We assessed the vaccination effectiveness (VE) of a COVID-19 booster vaccine dose and the association between morbidity and absenteeism with COVID-19 booster vaccine receipt among healthcare personnel (HCP) in 2022–2023 in Greece. We followed 5752 HCP from November 14, 2022 through May 28, 2023 for episodes of absenteeism. Absenteeism for non-infectious causes, pregnancy leave, or annual leave was not recorded. Full vaccination was defined as a primary vaccination series plus one booster dose within the past six months. Multivariable regression models were used to estimate the association of full COVID-19 vaccination with the outcomes of interest. A total of 1029 episodes of absenteeism occurred during the study period (17.9 episodes per 100 HCP). The mean duration of absence per episode was 5.2 days, and the total duration of absence was 5237 days. COVID-19 was diagnosed in 736 (12.8 %) HCP, asymptomatic SARS-CoV-2 infection in 62 (1.1 %) HCP, and influenza in 95 (1.7 %) HCP. Overall, COVID-19, influenza, and asymptomatic SARS-CoV-2 infection accounted for 71.5 %, 9.2 %, and 6.0 % of episodes of absenteeism, respectively. Multivariable regression models indicated that fully vaccinated HCP were absent from work for shorter periods [adjusted odds ratio (aOR): 0.42; 95 % confidence interval (CI): 0.21–0.83], were less likely to develop COVID-19 [aOR: 0.37; 95 % CI: 0.17–0.81)], and were more likely to develop an asymptomatic SARS-CoV-2 infection (aOR: 5.90; 95 % CI: 1.27–27.45). The adjusted full VE against COVID-19 was 62.8 % (95 % CI: 18.6 %-83.0 %). COVID-19 remains a significant cause of morbidity and absenteeism among HCP. Full COVID-19 vaccination status conferred significant protection against COVID-19 and was associated with shorter periods of absence from work. [ABSTRACT FROM AUTHOR]

Trust in governments and public institutions as a determinant of public health outcomes has gained increased attention since the COVID-19 pandemic. Provided historically low confidence in vaccines in Japan, investigating the role of trust in information sources and actual COVID-19 vaccination uptake behavior will be invaluable for future vaccine promotion policymaking. Therefore, the objective of this study was to elucidate the determinants of COVID-19 vaccination uptake and evaluate the relationship between trust in different information sources and COVID-19 vaccination behavior in Japan. For this study, we leveraged a longitudinal series of web-based surveys of 19,174 individuals in Japan conducted between 2021 and 2022 which asked questions regarding a wide range of sociodemographic and psychographic characteristics related to the COVID-19 pandemic. Determinant analysis for vaccination (at least one dose of a COVID-19 vaccine) was conducted via multiple logistic regression, and odds ratios (OR) with 95% confidence intervals (CI) were estimated. After adjustment for sociodemographic determinants of vaccine uptake, aggregate trust in the systems and institutions of vaccine approval (OR: 1.42, 95% CI: 1.30–1.56), and trust in information about the COVID-19 pandemic coming from government sources (OR: 1.27, 95% CI: 1.12–1.44) were found to be consistently powerful predictors of COVID-19 vaccination. Trust in media sources including traditional media (OR: 1.21, 95% CI: 1.07–1.36), and the internet (OR: 0.77, 95% CI: 0.66–0.89) had significant and opposing effects. Our findings support the broader hypothesis that trust in governments and public health institutions remains a powerful determinant for COVID-19 vaccine uptake in Japan. We also found that vaccination decision-making is a multifactorial process that includes the synthesis of trust in public institutions and media, and its interaction with psychosocial determinants such as prosociality and health literacy. We hope to apply this study's findings towards future vaccine programs for contagious diseases. [ABSTRACT FROM AUTHOR]

With the continuous emergence of coronavirus disease 2019 (COVID-19) waves, the scientific community has developed a vaccine that offers broad-spectrum protection at virus-targeted organs for inhibiting the transmission and protection of disease development. In the present study, a bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine containing receptor-binding domain (RBD) protein of spike from Wuhan-1 and omicron BA.1 loaded in nanoparticles, bivalent RBD NPs, was developed. The immunogenicity and protective efficacy of this vaccine candidate were evaluated using an in vivo model. Results showed that mice that received intranasal cGAMP-adjuvanted bivalent RBD-NPs vaccine elicited robust and durable antibody responses. The stimulated antibody broadly neutralized the ancestral strain and variants of concerns (delta and omicron BA.1) in the upper and lower respiratory tracts. Furthermore, the immunized mice developed T-cell response in their lung tissue. Importantly, intranasal immunization with this vaccine candidate efficiently protected mice from nasal infection caused by both Wuhan-1 and BA.1 viruses. Immunized mice that remained susceptible to nasal infection did not develop any symptoms. This is because activated responses in the nasal cavity significantly suppressed virus production. Another word is this nasal vaccine completely protected the mice from disease development and mortality. Therefore, the bivalent RBD vaccine platform has potential to be developed into an anti-SARS-CoV-2 universal vaccine. [ABSTRACT FROM AUTHOR]

Vaccine prevention strategies play a crucial role in the management of people living with HIV (PLWH). The aim of this study was to assess vaccination coverage and identify barriers to vaccine uptake in PLWH in the Paris region. A cross-sectional survey was conducted in PLWH in 16 hospitals in the Paris region. The vaccination status, characteristics, opinions, and behaviors of participants were collected using a face-to-face questionnaire and from medical records. A total of 338 PLWH were included (response rate 99.7 %). The median age of participants was 51 years (IQR: 41–58). Vaccination coverage was 77.3 % for hepatitis B (95 % CI: 72.3–81.8 %), 62.7 % for hepatitis A (57.3–67.9 %), 61.2 % for pneumococcal vaccines (55.8–66.5 %), 56.5 % for diphtheria/tetanus/poliomyelitis (DTP) (51.0–61.9 %), 44.7 % for seasonal influenza (39.3–50.1 %), 31.4 % for measles/mumps/rubella (26.4–36.6 %) and 38.5 % for meningococcal vaccine (13.9–68.4 %). The main reason for vaccine reluctance was related to the lack of vaccination proposals/reminders. The overall willingness to get vaccinated was 71.0 % (65.9–75.8 %). In the multivariable analysis, several factors were associated with a higher vaccine uptake; for DTP vaccine: higher education level, having vaccination records, being registered with a general practitioner; for seasonal influenza vaccine: age > 60 years, higher education level, being employed. The overall vaccination coverage was suboptimal. Development of strategies reducing missed opportunity to offer vaccines is needed. [ABSTRACT FROM AUTHOR]

Most studies examining factors associated with pediatric influenza (flu) and coronavirus disease (COVID-19) vaccination uptake focus on parental demographics. We examined whether the childhood cultural health environment (CHE) of parents (measured by self-reported regular attendance at doctor and dentist visits during childhood) was associated with flu and COVID-19 vaccination of their children. Using 2023 survey data from 397 US parents and causal inference methods, we estimated the average causal effect of parental CHE on flu vaccination rates (0.16 [95 % confidence interval: 0.06,0.27]) and COVID-19 (0.14 [95 % confidence interval: 0.04,0.24]), indicating that if all parents had attended regular doctor/dentist visits as children, flu and COVID-19 vaccination rates in children would be 16 % and 14 % higher, respectively, than if none had. Our findings suggest that early life exposure to medical and dental care has significant and lasting effects on the health of individuals and families. [ABSTRACT FROM AUTHOR]

Measles remains a critical public health concern causing significant morbidity and mortality globally. Despite the success of measles vaccination programs, challenges persist, particularly in India. This study investigates dose-wise measles vaccination coverage and explores gaps in immunization focusing on zero-dose, one-dose, and two-dose coverage among children aged 24–35 months. The National Family Health Survey 2019–21 (NFHS-5) served as the data source and the study analyzed information from 43,864 children aged 24–35 months. Sociodemographic variables such as birth order, wealth quintile, gender, social group, religion, residence, mother education, delivery-related factors, and media exposure were considered. Statistical analysis involved weighted estimates, chi-square tests, and multivariate multinomial logistic regression. The study revealed that challenges persist in achieving optimal measles vaccination coverage. Analysis by sociodemographic factors highlighted disparities in coverage, with variations in zero dose prevalence across states and districts. The percentage of zero-dose children was significantly higher, with 11.5% of children in India remaining to receive any measles vaccination. Factors influencing vaccine coverage include birth order, age, wealth quintile, social group, religion, residence, maternal education, place of delivery, media exposure, and mode of delivery. The findings from the spatial analysis show the clustering of zero-dose children is high in the northeastern states of India. Measles zero-dose children pose a significant obstacle to achieving elimination goals. Spatial analysis identifies clusters of unvaccinated populations guiding targeted interventions. The study aligns with global initiatives such as the Immunization Agenda 2030 emphasizing equitable vaccine access and discusses how India can tailor its strategies to achieve the goal. Lessons from polio eradication efforts inform strategies for measles elimination, stressing the importance of high-quality data and surveillance. The study underscores the urgency of addressing last-mile measles vaccination gaps in India. Spatially targeted interventions informed by sociodemographic factors can enhance immunization coverage. Achieving measles elimination requires sustained efforts and leveraging lessons from successful vaccination campaigns. The study findings have the potential to contribute to informed decision-making, supporting India's roadmap for the measles and rubella elimination goal. [ABSTRACT FROM AUTHOR]

Background In 2020, the Council of State and Territorial Epidemiologists (CSTE) pertussis case definition was modified; the main change was classifying polymerase chain reaction (PCR)-positive cases as confirmed, regardless of cough duration. Pertussis data reported through Enhanced Pertussis Surveillance (EPS) in 7 sites and the National Notifiable Diseases Surveillance System (NNDSS) were used to evaluate the impact of the new case definition. Methods We compared the number of EPS cases with cough onset in 2020 to the number that would have been reported based on the prior (2014) CSTE case definition. To assess the impact of the change nationally, the proportion of EPS cases newly reportable under the 2020 CSTE case definition was applied to 2020 NNDSS data to estimate how many additional cases were captured nationally. Results Among 442 confirmed and probable cases reported to EPS states in 2020, 42 (9.5%) were newly reportable according to the 2020 case definition. Applying this proportion to the 6124 confirmed and probable cases reported nationally in 2020, we estimated that the new definition added 582 cases. Had the case definition not changed, reported cases in 2020 would have decreased by 70% from 2019; the observed decrease was 67%. Conclusions Despite a substantial decrease in reported pertussis cases in the setting of coronavirus disease 2019 (COVID-19), our data show that the 2020 pertussis case definition change resulted in additional case reporting compared with the previous case definition, providing greater opportunities for public health interventions such as prophylaxis of close contacts. [ABSTRACT FROM AUTHOR]

Introduction A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. Methods Healthy adults (n = 180), ages 19–50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed. Results Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6–212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval. Conclusions Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807. [ABSTRACT FROM AUTHOR]

Background A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman–Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®). Methods This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5 IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was >−5% at D28. Safety was assessed up to 6 months after the last injection. Results Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5 IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines. Conclusions In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines. Clinical Trials Registration NCT03965962. [ABSTRACT FROM AUTHOR]

Background The adjuvanted RSV prefusion F protein–based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post–dose 1. Methods In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre–season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre–season 2; participants who received placebo pre–season 1 received placebo pre–season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided CIs around efficacy estimates >20%). Results The efficacy analysis comprised 24 967 participants (RSV_1dose: 6227; RSV_revaccination: 6242; placebo: 12 498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2–80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6–92.0%) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1–80.0%) against RSV-LRTD and 78.8% (95% CI: 52.5–92.0%) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1. Conclusions One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post–dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population. Clinical Trials Registration ClinicalTrials.gov: NCT04886596. [ABSTRACT FROM AUTHOR]

Current serologic tests for HIV screening and confirmation of infection present challenges to the adoption of HIV vaccines. The detection of vaccine-induced HIV-1 antibodies in the absence of HIV-1 infection, referred to as vaccine-induced seropositivity/seroreactivity, confounds the interpretation of test results, causing misclassification of HIV-1 status with potential affiliated stigmatization. For HIV vaccines to be widely adopted with high community confidence and uptake, tests are needed that are agnostic to the vaccination status of tested individuals (ie, positive only for true HIV-1 infection). Successful development and deployment of such tests will require HIV vaccine developers to work in concert with diagnostic developers. Such tests will need to match today's high-performance standards (accuracy, cost-effectiveness, simplicity) for use in vaccinated and unvaccinated populations, especially in low- and middle-income countries with high HIV burden. Herein, we discuss the challenges and strategies for developing modified serologic HIV tests for concurrent deployment with HIV vaccines. [ABSTRACT FROM AUTHOR]

Background Plasmodium falciparum and Plasmodium vivax account for >90% global malaria burden. Transmission intervention strategies encompassing transmission-blocking vaccines (TBV) and drugs represent ideal public health tools to eliminate malaria at the population level. The availability of mature P. falciparum gametocytes through in vitro culture has facilitated development of a standard membrane feeding assay to assess efficacy of transmission interventions against P. falciparum. The lack of in vitro culture for P. vivax has significantly hampered similar progress on P. vivax and limited studies have been possible using blood from infected patients in endemic areas. The ethical and logistical limitations of on-time access to blood from patients have impeded the development of P. vivax TBVs. Methods Transgenic murine malaria parasites (Plasmodium berghei) expressing TBV candidates offer a promising alternative for evaluation of P. vivax TBVs through in vivo studies in mice, and ex vivo membrane feeding assay (MFA). Results We describe the development of transmission-competent transgenic TgPbvs25 parasites and optimization of parameters to establish an ex vivo MFA to evaluate P. vivax TBV based on Pvs25 antigen. Conclusions The MFA is expected to expedite Pvs25-based TBV development without dependence on blood from P. vivax -infected patients in endemic areas for evaluation. [ABSTRACT FROM AUTHOR]

Background Malaria is preventable yet causes >600 000 deaths annually. RTS,S, the first marketed malaria vaccine, has modest efficacy, but improvements are needed for eradication. Methods We conducted an open-label, dose escalation phase 1 study of a full-length recombinant circumsporozoite protein vaccine (rCSP) administered with adjuvant glucopyranosyl lipid A–liposome Quillaja saponaria 21 formulation (GLA-LSQ) on days 1, 29, and 85 or 1 and 490 to healthy, malaria-naive adults. The primary end points were safety and reactogenicity. The secondary end points were antibody responses and Plasmodium falciparum parasitemia after homologous controlled human malaria infection. Results Participants were enrolled into 4 groups receiving rCSP/GLA-LSQ: 10 µg × 3 (n = 20), 30 µg × 3 (n = 10), 60 µg × 3 (n = 10), or 60 µg × 2 (n = 9); 10 participants received 30 µg rCSP alone × 3, and there were 6 infectivity controls. Participants experienced no serious adverse events. Rates of solicited and unsolicited adverse events were similar among groups. All 26 participants who underwent controlled human malaria infection 28 days after final vaccinations developed malaria. Increasing vaccine doses induced higher immunoglobulin G titers but did not achieve previously established RTS,S benchmarks. Conclusions rCSP/GLA-LSQ had favorable safety results. However, tested regimens did not induce protective immunity. Further investigation could assess whether adjuvant or schedule adjustments improve efficacy. Clinical Trials Registration NCT03589794 [ABSTRACT FROM AUTHOR]

Next-generation pneumococcal conjugate vaccines (PCVs) have been approved for use. The serotype distribution of pneumococcal isolates can vary between regions. To understand the potential impacts of new PCVs, we evaluated trends in invasive pneumococcal disease (IPD) among adults in Germany at a local level using Bayesian hierarchical logistic regression. There was little spatial variation in IPD cases caused by 13-valent PCV serotypes, which dropped from 60% of IPD cases in 2006 to 30% in 2018. More than half of IPD cases in 2018 were attributable to serotypes covered by new PCVs (15-valent and 20-valent PCVs), which suggests they could further reduce the burden of IPD. [ABSTRACT FROM AUTHOR]

Background Variability in vaccine responsiveness among young children is poorly understood. Methods Nasopharyngeal secretions were collected in the first weeks of life for measurement of cytokines/chemokines seeking a biomarker, and blood samples were collected at age 1 year to identify vaccine responsiveness status, defined as low vaccine responder (LVR), normal vaccine responder (NVR), and high vaccine responder (HVR), to test for vaccine antigen–induced immune memory and for antigen-presenting cell (APC) function. Results Significantly lower specific cytokine/chemokine levels as biosignatures, measurable in nasopharyngeal secretions at infant age 1–3 weeks, predicted LVR status compared to NVR and HVR children. Antibiotic exposures were correlated with increased occurrence of LVR. At age 1 year, LVRs had fewer CD4+ T-helper 1 and T-helper 2 memory cells responsive to specific vaccine antigens. APC responses observed among LVRs, both at rest and in response to Toll-like receptor 7/8 stimulation by R848, were suboptimal, suggesting that altered innate immunity may contribute to immune deficiency in LVRs. Conclusions Cytokine biosignatures in the first weeks of life may predict vaccine responsiveness in children during the first year of life. Antibiotic exposure is associated with LVR in children. CD4+ T-cell memory induction and APC deficiencies occur in LVR children. [ABSTRACT FROM AUTHOR]

Summary: Splenectomy is an effective treatment for immune thrombocytopenia (ITP). The effect of COVID‐19 vaccination on splenectomized patients with ITP during the COVID‐19 pandemic has not been reported. Therefore, this study aimed to investigate the effect of COVID‐19 vaccination on clinical outcomes in these patients. This was a longitudinal study of splenectomized patients with ITP. A total of 191 splenectomized patients were included in this study. After a median follow‐up of 114 months, 146 (76.4%) patients had a sustained response to splenectomy. During COVID‐19 infection, vaccinated patients showed a lower risk of severe infections (odds ratio [OR], 0.13; 95% confidence interval [CI]: 0.05–0.36; p < 0.001), hospitalization (OR, 0.13; 95% CI, 0.04–0.48; p = 0.002), and ITP exacerbation (OR, 0.16; 95% CI, 0.04–0.67; p = 0.012). These findings indicate that COVID‐19 vaccination plays a protective role in splenectomized patients with ITP. [ABSTRACT FROM AUTHOR]

The 2021 tuberculosis (TB) preventive treatment guidelines in India included silicosis as a screening group, yet latent TB infection (LTBI) testing for silica-dust-exposed individuals is underemphasized. Focusing on an estimated 52 million silica-dust-exposed workers, particularly agate-stone workers in Khambhat, Gujarat, our study aims to estimate LTBI prevalence, identify predictors, and gather insights from TB and silicosis experts. Employing a sequential explanatory mixed-methods approach, a cross-sectional study involved 463 agate-stone workers aged ≥ 20 years in Khambhat, using IGRA kits for LTBI testing. In-depth interviews with experts complemented quantitative findings. Among agate-stone workers, 58% tested positive for LTBI, with predictors including longer exposure, type of work, and BCG vaccination. Our findings reveal a nearly double burden of LTBI compared to the general population, particularly in occupations with higher silica dust exposure. Experts advocate for including silica-dust-exposed individuals in high-risk groups for LTBI testing, exploring cost-effective alternatives like improved skin sensitivity tests, and shorter TB preventive treatment regimens to enhance compliance. Future research should explore upfront TB preventive treatment for silica-dust-exposed individuals with high LTBI prevalence and optimal exposure duration. This study underscores the urgent need for policy changes and innovative approaches to TB prevention among silica-dust-exposed populations, impacting global occupational health strategies. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 had devastating consequences for human health. Despite the introduction of several vaccines, COVID-19 continues to pose a serious health risk due to emerging variants of concern. DNA vaccines gained importance during the pandemic due to their advantages such as induction of both arms of immune response, rapid development, stability, and safety profiles. Here, we report the immunogenicity and protective efficacy of a DNA vaccine encoding spike protein with D614G mutation (named pcoSpikeD614G) and define a large-scale production process. According to the in vitro studies, pcoSpikeD614G expressed abundant spike protein in HEK293T cells. After the administration of pcoSpikeD614G to BALB/c mice through intramuscular (IM) route and intradermal route using an electroporation device (ID + EP), it induced high level of anti-S1 IgG and neutralizing antibodies (P < 0.0001), strong Th1-biased immune response as shown by IgG2a polarization (P < 0.01), increase in IFN-γ levels (P < 0.01), and increment in the ratio of IFN-γ secreting CD4+ (3.78–10.19%) and CD8+ (5.24–12.51%) T cells. Challenging K18-hACE2 transgenic mice showed that pcoSpikeD614G administered through IM and ID + EP routes conferred 90–100% protection and there was no sign of pneumonia. Subsequently, pcoSpikeD614G was evaluated as a promising DNA vaccine candidate and scale-up studies were performed. Accordingly, a large-scale production process was described, including a 36 h fermentation process of E. coli DH5α cells containing pcoSpikeD614G resulting in a wet cell weight of 242 g/L and a three-step chromatography for purification of the pcoSpikeD614G DNA vaccine. [ABSTRACT FROM AUTHOR]