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AbstractObjectiveMethodsResultsConclusionTo investigate the safety of COVID-19 inactivated vaccine in immature mice.We selected 3-week-old immature BALB/c mice, continuously observed until 7 weeks old after continuous immunization with fully inactivated vaccine (initial strengthening), and sacrificed BALB/c mice at 7 weeks old, and used H&E, Masson, mast cells and Ki-67 staining to analyze the changes of heart, liver, spleen, kidney, lung and brain. In addition, RNA was extracted from important organs such as the heart, liver, spleen, kidney, lung, and brain, and to evaluate whether there was any effect after vaccination through bulk-RNA sequencing.After H&E, Masson, mast cells and Ki-67 staining analyses, there are no significant differences between tissues and organs in the vaccine group and the PBS group, and RNA-Seq did not show that the vaccine had any effect on immature mice.COVID-19 inactivated vaccine is safe in immature mice. [ABSTRACT FROM AUTHOR]

Largemouth bass (Micropterus salmoides) is an economically important fish, yet it is plagued by frequent diseases caused by Aeromonas veronii infection in its aquaculture. Vaccination is a pivotal strategy in the prevention and management of infectious diseases, and adjuvants play a crucial role in augmenting the effectiveness of vaccines. Interleukin-8 (IL-8), one of the CXC chemokines, has been identified as having adjuvant potential in various species, although its efficacy in largemouth bass remains uncertain. In the present study, recombinant largemouth bass IL-8 (rLbIL-8) was prepared to explore its adjuvant potential in the A. veronii inactivated vaccine. Challenge experiment results revealed that the relative percent survival (RPS) of largemouth bass in the inactivated A. veronii + rLbIL-8 vaccinated group was calculated to be 70% following challenges with live A. veronii, higher than that of the inactivated A. veronii vaccinated group (56.67%). Furthermore, co-inoculation of rLbIL-8 and inactivated A. veronii markedly elevated serum SOD levels and lysozyme activities in largemouth bass. Indirect ELISA analysis found that rLbIL-8 enhanced the inactivated A. veronii vaccine's ability to induce serum-specific antibodies against A. veronii. qRT-PCR analysis showed that rLbIL-8 enhanced the upregulation of IL-1β, TNF-α, CD4, MHC II, and IgM expression induced by inactivated A. veronii, with peak expression occurring on days 1 and 5 post-vaccination, respectively. Collectively, these findings attest to the potential of rLbIL-8 as a vaccine adjuvant for largemouth bass, advancing the progress and implementation of vaccines in aquaculture. [ABSTRACT FROM AUTHOR]

Background: To estimate vaccine effectiveness(VE) against COVID-19-related hospitalization for inactivated vaccines during the Omicron BF.7-predominant epidemic wave in Beijing, China. Methods: We recruited a cohort in Beijing on 17 and 18 December 2022, collected status of vaccination and COVID-19-related hospitalization since 1 November 2022 and prospectively followed until 9 January 2023. A Poisson regression model was used to estimate the VE. Results: 16(1.15%) COVID-19-related hospitalizations were reported in 1391 unvaccinated participants; 7(0.25%) in 2765 participants with two doses, resulting in a VE of 70.89%(95% confidence interval[CI] 26.25 to 87.73); 32(0.27%) in 11,846 participants with three doses, with a VE of 65.25%(95% CI 32.24 to 81.83). The VE of three doses remained above 64% at 1 year or more since the last dose. Elderly people aged ≥ 60 years had the highest hospitalization incidence(0.66%), VE for two doses was 74.11%(95%CI: − 18.42 to 94.34) and VE for three doses was 80.98%(95%CI:52.83 to 92.33). We estimated that vaccination had averted 65,007(95%CI: 12,817 to 97,757) COVID-19-related hospitalizations among people aged ≥ 60 years during the BF.7-predominant period in Beijing. Conclusion: Inactivated COVID-19 vaccines were effective against COVID-19-related hospitalization, especially for the elderly population who have increased risk of severe disease owing to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Objective To explore the dynamic changes of anti-coronavirus antibodies in medical staff of intensive care unit after three doses of novel coronavirus inactivated vaccine, and to dynamically evaluate their immune status. Methods A total of 30 medical staff in intensive care unit who received three doses of inactivated SARS-CoV-2 vaccine in this hospital from November 2020 to November 2021 were selected as the research objects. Venous blood samples were collected at 0, 1, 3, 6 and 12 months after inoculation of novel coronavirus vaccine to detect the titer of anti-novel, coronavirus antibody immunoglobulin G, lymphocyte subsets and cytokines, and the changes were analyzed. Results Anti-coronavirus antibodies were positive in 30 medical staff one month after injection of three doses of inactivated coronavirus vaccine, and the titer increased significantly in the first month, with statistically significant difference (P＜0. 05). In the first month, the anti-neo-coronavirus antibody reached a peak and then gradually decreased. In the 12th month, the anti-neo-coronavirus antibody was still higher than that in the 0 th month, and the difference was statistically significant (P＜0. 05). There was no significant difference in lymphocyte subsets at different time points (P＞0. 05). After inoculation with the novel coronavirus inactivated vaccine, interleukin-2 (IL-2), IL-10, interferon-γ, and tumor necrosis factor-α all showed inverted U-shaped changes, IL-6 showed U-shaped changes, and IL-4 showed fluctuating changes. Conclusion The three-dose inactivated vaccine can produce a higher level of antibody and maintain a high titer for at least six months. [ABSTRACT FROM AUTHOR]

Background: Pregnancy is a critical time for women, making them more susceptible to infectious diseases like COVID-19. This study aims to determine the immunogenicity of COVID-19 in pregnant women who have been infected compared to those who have received the inactive COVID-19 vaccine. Materials and methods: In this retrospective cohort study, pregnant women who received the inactivated COVID-19 vaccine (Sinopharm) and those with a history of COVID-19 infection during pregnancy were studied. Participants who had experienced stillbirth, received different COVID-19 vaccines, or had intrauterine fetal death were excluded from the study. Overall, the study included 140 participants. The participants were divided into two groups of 70 participants - pregnant women who received the Sinopharm vaccine and pregnant women who had COVID-19 infection during pregnancy. Before delivery, blood samples were collected from all mothers to evaluate the maternal immunoglobulin G (IgG) level. Blood samples were also taken from the baby's umbilical cord during delivery to measure the newborn's IgG level. Additionally, blood samples were collected from babies whose mothers showed signs of acute infection to measure their IgM levels and evaluate vertical transmission. Findings: The study found a significant relationship between the mean level of maternal IgG and umbilical cord IgG within the groups (P < 0.001). The highest levels of maternal IgG (2.50 ± 2.17) and umbilical cord IgG (2.43 ± 2.09) were observed in pregnant women with a previous COVID-19 infection and no history of vaccination (P < 0.001). Only one baby was born with a positive IgM, and this baby was born to a mother who showed signs of COVID-19 infection in the last five days of pregnancy. The mother was 28 years old, with a BMI of 33; it was her first pregnancy, and she gave birth to a male newborn at term. Conclusion: Administering an inactivated vaccine during pregnancy can generate immunity in both the mother and the child. However, the vaccine's immunity level may not be as potent as that conferred by COVID-19 infection during pregnancy. Nonetheless, the risk of vertical transmission of COVID-19 is considered minimal and can be classified as negligible. [ABSTRACT FROM AUTHOR]

The safety of the mRNA and inactivated SARS-CoV-2 vaccine has been demonstrated for people living with HIV (PLHIV). However, vaccine studies in PLHIV are limited, and there is a gap in which vaccine type provides the best response in PLHIV. Thus, PLHIV may benefit from mRNA vaccine types compared to inactivated vaccines. This study aims to assess the immune responses to vaccination by measuring specific antibodies (IgG) targeting the receptor binding sites (RBDs) of the SARS-CoV-2 virus and the levels of IL-2 and IFN-γ in plasma. A total of 41 PLHIV who regularly take antiretroviral therapy (ART) over a period of six months, along with 31 individuals in a healthy control group (HC), were administered either two mRNA or inactivated vaccines. Data regarding demographics and clinical information were gathered from the medical records. An analysis was conducted on the neutralisation antibody IgG specific to RBD using the chemiluminescence microparticle assay (CMIA). The levels of IL-2 and IFN-γ were quantified using the Luminex assay method from plasma samples. Data were collected in the laboratory 28 days after each vaccination. After the first vaccination, the level of anti-SARS-CoV-2 RBD IgG was higher in PLHIV who received the mRNA vaccines than those who received inactivated vaccines (p = 0.006). The levels of mRNA in the PLHIV group showed a significant correlation with IL-2 and IFN-γ after the second vaccination (r = 0.51, p = 0.0035; r = 0.68, p = 0.002). The group of PLHIV who received the inactivated vaccine showed increased IL-2 and IFN-γ after the initial vaccination, compared to PLHIV who received the mRNA vaccine (p = 0.04; p = 0.08). Administering a two-dose vaccination is essential to increase the levels of neutralising antibodies significantly (p = 0.013) in PLHIV who have received inactivated vaccines; further study is needed to make this a recommendation. The responses observed after vaccination in PLHIV were not affected by their CD4 cell counts. PLHIV showed higher levels of SARS-CoV-2 IgG and increased IL-2 and IFN-γ levels. Our study encourages SARS-CoV-2 vaccination in PLHIV regardless of its CD4 cell counts. Furthermore, the mRNA vaccine may give robust high antibody responses in PLHIV. [ABSTRACT FROM AUTHOR]

Caseous lymphadenitis (CLA) is a chronic and subclinical bacterial disease of ruminants caused by Corynebacterium pseudotuberculosis (C. pseudotuberculosis) infection. Until 2014, there were no reports of CLA outbreaks in South Korea; however, the prevalence of CLA cases has steadily increased. In this study, we used recently obtained field isolates to develop the first inactivated CLA vaccine in South Korea and evaluated it in various animal models. The inactivated vaccine was evaluated for virulence and effectiveness. Mice were tested for virulence and immunization challenges, and guinea pigs and Korean Native Black Goats (KNBGs) evaluated various vaccine concentrations to determine the optimal dose and effectiveness. In the case of KNBGs, clinical symptoms were not observed after vaccination. In addition, CLA-specific IgG was detected at a significantly (p < 0.05) high level and was maintained. In histopathological evaluations, inflammation was predominantly observed in the prefemoral lymph nodes in the non-vaccinated+CHAL group. The genetic diversity of C. pseudotuberculosis, which has become widespread in South Korea, is less than 0.5% our vaccine is expected to prevent infection by a wide range of strains effectively. In summary, our CLA vaccine can potentially prevent CLA and foster the growth of South Korea's domestic KNBG industry. [ABSTRACT FROM AUTHOR]

Abstract Vaccination has been widely recognized as an effective measure for preventing infectious diseases. To facilitate quantitative research into the activation of adaptive immune responses in the human body by vaccines, it is important to develop an appropriate mathematical model, which can provide valuable guidance for vaccine development. In this study, we constructed a novel mathematical model to simulate the dynamics of antibody levels following vaccination, based on principles from immunology. Our model offers a concise and accurate representation of the kinetics of antibody response. We conducted a comparative analysis of antibody dynamics within the body after administering several common vaccines, including traditional inactivated vaccines, mRNA vaccines, and future attenuated vaccines based on defective interfering viral particles (DVG). Our findings suggest that booster shots play a crucial role in enhancing Immunoglobulin G (IgG) antibody levels, and we provide a detailed discussion on the advantages and disadvantages of different vaccine types. From a mathematical standpoint, our model proposes four essential approaches to guide vaccine design: enhancing antigenic T-cell immunogenicity, directing the production of high-affinity antibodies, reducing the rate of IgG decay, and lowering the peak level of vaccine antigen-antibody complexes. Our study contributes to the understanding of vaccine design and its application by explaining various phenomena and providing guidance in comprehending the interactions between antibodies and antigens during the immune process.

“ARRIAH-AviFluVac” vaccine against H5 avian influenza was demonstrated to be effective for ducks, geese and turkeys both in the laboratory and production environment. When administered to ducks at 0.5; 1.0 and 1.5 cm3, the vaccine provided 100%-effective protection of birds against the disease and death after challenge with the relevant high pathogenicity avian influenza virus of subtype H5N1, clade 2.3.4.4b. Singular 0.5–1.5 cm3 inoculation induced formation of antibodies, which were detected in the hemagglutination inhibition test at the titres that ranged from 4.3 to 6.1 log2. The vaccine facilitated 9–26-fold decrease in the virulent virus shedding by the ducks. Protection of turkeys vaccinated at the dose of 1.0 cm3 was maintained at the level of 87.5% after challenge with high pathogenicity avian influenza virus of subtype H5N1, clade 2.3.4.4b. The vaccine induced formation of antibodies at the titres of 4.9 and 5.5 log2 in turkeys after singular and double vaccination at the dose of 1.0 cm3, respectively. It was demonstrated, that after double administration of 1.0 cm3 of “ARRIAH-AviFluVac” vaccine, the post-vaccinal avian influenza antibody level exceeded 5.0 log2 in 75.9–90.0% of the geese population. The most appropriate way of the vaccine use in turkeys, ducks and geese involves at least its double administration at the double commercial dose. Higher species resistance of ducks to the challenge with avian influenza virus of subtype H5, clade 2.3.4.4bas compared to turkeys was also demonstrated.

Abstract Background To estimate vaccine effectiveness(VE) against COVID-19-related hospitalization for inactivated vaccines during the Omicron BF.7-predominant epidemic wave in Beijing, China. Methods We recruited a cohort in Beijing on 17 and 18 December 2022, collected status of vaccination and COVID-19-related hospitalization since 1 November 2022 and prospectively followed until 9 January 2023. A Poisson regression model was used to estimate the VE. Results 16(1.15%) COVID-19-related hospitalizations were reported in 1391 unvaccinated participants; 7(0.25%) in 2765 participants with two doses, resulting in a VE of 70.89%(95% confidence interval[CI] 26.25 to 87.73); 32(0.27%) in 11,846 participants with three doses, with a VE of 65.25%(95% CI 32.24 to 81.83). The VE of three doses remained above 64% at 1 year or more since the last dose. Elderly people aged ≥ 60 years had the highest hospitalization incidence(0.66%), VE for two doses was 74.11%(95%CI: − 18.42 to 94.34) and VE for three doses was 80.98%(95%CI:52.83 to 92.33). We estimated that vaccination had averted 65,007(95%CI: 12,817 to 97,757) COVID-19-related hospitalizations among people aged ≥ 60 years during the BF.7-predominant period in Beijing. Conclusion Inactivated COVID-19 vaccines were effective against COVID-19-related hospitalization, especially for the elderly population who have increased risk of severe disease owing to SARS-CoV-2 infection.

Abstract Background Pregnancy is a critical time for women, making them more susceptible to infectious diseases like COVID-19. This study aims to determine the immunogenicity of COVID-19 in pregnant women who have been infected compared to those who have received the inactive COVID-19 vaccine. Materials and methods In this retrospective cohort study, pregnant women who received the inactivated COVID-19 vaccine (Sinopharm) and those with a history of COVID-19 infection during pregnancy were studied. Participants who had experienced stillbirth, received different COVID-19 vaccines, or had intrauterine fetal death were excluded from the study. Overall, the study included 140 participants. The participants were divided into two groups of 70 participants - pregnant women who received the Sinopharm vaccine and pregnant women who had COVID-19 infection during pregnancy. Before delivery, blood samples were collected from all mothers to evaluate the maternal immunoglobulin G (IgG) level. Blood samples were also taken from the baby’s umbilical cord during delivery to measure the newborn’s IgG level. Additionally, blood samples were collected from babies whose mothers showed signs of acute infection to measure their IgM levels and evaluate vertical transmission. Findings The study found a significant relationship between the mean level of maternal IgG and umbilical cord IgG within the groups (P

Background: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients. Methods: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information. Results: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%. Conclusions: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination. [ABSTRACT FROM AUTHOR]

Various vaccine platforms have been approved for broad use to prevent the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, these vaccines exhibit distinct differences in immunogenicity and efficacy, which decline after vaccination and are further exacerbated by the emergence of virus variants and mutants. This study reports the immunization outcomes against the SARS-CoV-2 virus by assessing the immune responses and safety of different SARS-CoV-2 vaccines co-administered in BALB/c mice. Vaccine combinations comprising mRNA/adenovirus26-vector, mRNA/inactivated, adenovirus26-vector/inactivated, and mRNA/adenovirus26-vector/inactivated vaccines were prepared in optimized doses, and their activities upon immunization evaluated in comparison with individual mRNA, adenovirus26-vectored, and inactivated vaccines. Fourteen- and 28-days post-immunization, we measured spike-specific IgG response using Enzyme-Linked Immunosorbent Assay (ELISA), cytokine expression profiles through Quantitative real-time polymerase chain reaction (RT-PCR), and evaluated safety through histopathological examination. The mRNA/Vector/Inactivated group exhibited slightly higher anti-spike IgG levels, albeit not statistically significant (p > 0.132). Importantly, this regimen induced elevated IL-6 and IFN-γ mRNA expression levels (p < 0.0001) compared to immunization with individual vaccines. In summary, this study demonstrated that co-administering the mRNA/adenovirus26 vector/inactivated SARS-CoV-2 vaccines improved spike-specific IgG response, triggered significantly enhanced IL-6 and IFN-γ mRNA expression levels, and proved safe in mice.

Senecavirus A (SVA) is a picornavirus that is endemic in swine, causing a vesicular disease clinically indistinguishable from other vesicular diseases, like foot-and-mouth disease. The widespread viral circulation, constant evolution, and economic losses caused to the swine industry emphasize the need for measures to control the agent. In this study, we evaluated the immunogenicity of a whole-virus-inactivated vaccine using a representative contemporary Brazilian SVA strain in Balb/ByJ mice. The animals were vaccinated with two doses by an intramuscular route. The humoral response induced by the vaccination was evaluated by an in-house ELISA assay for IgG detection. The cellular response was assessed by flow cytometry after in vitro SVA stimulation in splenocyte cultures from vaccinated and non-vaccinated groups. Protection against SVA was assessed in the experimental groups following an oral challenge with the homologous virus. The vaccination induced high levels of IgG antibodies and the proliferation of CD45R/B220+sIgM+, CD3e+CD69+, and CD3e+CD4+CD44+CD62L− cells. These results indicate the immunogenicity and safety of the vaccine formulation in a murine model and the induction of humoral and cellular response against SVA. [ABSTRACT FROM AUTHOR]

The extensive growth of intensive fish farming has led to a massive spread of infectious diseases. Nervous necrosis virus (NNV) is the causative agent of the viral encephalo‐ and retinopathy disease which has become a major threat for fish farming all over the globe. The devastating mortality rates recorded in disease outbreaks, especially when infected specimens are at early stages of development, have a high economic impact on the sector. Currently, vaccines are the most cost‐effective preventing tool in the fight against viruses. Inactivated vaccines have the advantage of simplicity in their development at the same time as present the antigen in a similar manner than the natural infection in the host. Nevertheless, they usually trigger weaker immune responses needing adjuvants to boost their effectiveness. In this work, we have intraperitoneally vaccinated Senegalese sole juveniles (Solea senegalensis) with a previously designed inactivated vaccine against NNV based on binary ethylenimine (BEI), mixed or not with an oil‐adjuvant. Our results demonstrated the potential activation of different immune pathways when the vaccine was administered alone compared to the oil‐adjuvanted vaccine, both resulting in an equivalent partial improvement in survival following a NNV challenge. However, whilst the vaccine alone led to a significant increase in specific antibodies, in the adjuvanted version those antibodies were kept basal although with a slight improvement in their neutralization capacity. At transcriptional level, neither vaccine (adjuvanted or not) triggered the immune system activation during the vaccination period. However, after NNV infection, the BEI‐inactivated vaccines alone and oil‐adjuvanted both elicited the stimulation of antiviral responsive genes (rtp3, herc4), antigen presentation molecules (mhcii) and T‐cell markers (cd8a) in the head‐kidney. Additionally, the oil‐adjuvanted vaccine appears to stimulate mediator cytokines (il6) and B‐cell markers (ight and ighm). Surprisingly, when the adjuvant was administered alone, fish showed the highest survival rates concomitantly with a lack of NNV‐IgM production, pointing to the possible induction of different immune pathways than the B‐cell responses via antibodies by the adjuvant. Since this combined vaccine did not succeed in the full extension of protection against the pathogen, further studies should be performed focusing on unravelling the molecular mechanisms through which adjuvants trigger the immune response, both independently and when added to a vaccine antigen. [ABSTRACT FROM AUTHOR]

Acquired hemophilia A (AHA) is a rare bleeding disorder (1.4 per million inhabitants per year) caused by neutralizing antibodies against factor VIII. Although uncommon, these autoantibodies can cause a high rate of morbidity and mortality. Several conditions are linked with AHA; based on an EACH2 study, 3.8% of AHA could be connected to infection. In the last four years, most humans have contracted the SARS-CoV-2 infection or have been vaccinated against it. Whether or not COVID-19 immunization might induce AHA remains controversial. This review aims to evaluate the evidence about this possible association. Overall, 18 manuscripts (2 case series and 16 case reports) were included. The anti-SARS-CoV-2 vaccination, as also happens with other vaccines, may stimulate an autoimmune response. However, older individuals with various comorbidities are both at risk of developing AHA and of COVID-19-related morbidity and mortality. Therefore, the COVID-19 vaccine must always be administered because the benefits still outweigh the risks. Yet, we should consider the rare possibility that the activation of an immunological response through vaccination may result in AHA. Detailed registries and prospective studies would be necessary to analyze this post-vaccine acquired bleeding disorder, looking for possible markers and underlying risk factors for developing the disease in association with vaccination. [ABSTRACT FROM AUTHOR]

Ornithobacterium rhinotracheale (ORT) is a gram-negative bacterium that causes respiratory infection in chickens and turkeys. The Co-infection of ORT with other viral or bacterial pathogens results in the development of severe clinical symptoms and significant economic losses. The proportion of ORT strains resistant to the current antibiotics employed in poultry flocks has increased in successive years. Contingent on the source of the isolate. It is recommended that the inactivated wholecell vaccine (bacterin) be administered against multi-drug resistant strains of ORT that are present on poultry farms. In the present study, a formalin-inactivated bacterin formulated with an oil adjuvant (MontanideTM ISA 70 VG) was developed based on a local ORT isolate. A prime-boost regimen was employed for the immunization of specific pathogen-free chicken (SPF) groups. Subsequently, the immunogenic potency of the vaccine candidate was evaluated via ELISA and compared with that of a Nobilis® commercial inactivated ORT vaccine.The safety of the Vaccine was studied following the inoculation of a dose that was twice the recommended dose of the prepared bacterin. The commercial inactivated ORT vaccine and the prepared bacterin both elicited the production of induced specific antibodies after three weeks following the initial vaccination, with this response continuing until 16 weeks postvaccination. The immunization of chickens with the commercial vaccine resulted in a higher level of antibody compared to the experimental vaccine. However, no significant difference (P<0.05) was observed between the treated groups overall. The safety test revealed the absence of any adverse local or systemic reactions were found in chickens throughout the post-vaccination period. The data indicate that the prepared ORT-inactivated vaccine is safe and capable of inducing adequate and longlasting immune responses in experimental SPF chickens. It is imperative to conduct field trials to ensure the efficacy of this vaccine candidate in preventing ORT infection. [ABSTRACT FROM AUTHOR]

Mineral oils are the most common adjuvants that are used in the production of poultry killed vaccine based on water-in-oil emulsion (W/O) to create high and long term antibody responses to vaccine antigens. The vaccine structural specifications, including particle size and formulation on stability and immunogenicity, have needed more clarification for vaccine producers so that they can produce their products based on highly efficient methods. This study assessed the effect of particle size on the stability and immunogenicity of a W/O vaccine. Different W/O emulsions were formulated by three different homogenization times by means of inactivated Avian Influenza Virus subtype H9N2 (AI H9N2) and Newcastle Disease Virus (V4) antigens and Montanide™ ISA 70 adjuvant. The three killed AI+ND vaccines were formulated and 2 commercial vaccines were evaluated for magnitude and duration of specific antibody response in SPF and broiler chickens. The vaccine dose for each bird was considered 0/2 ml. On days 7, 14 and 21 post vaccination, antibody titers of serum were evaluated by Hemagglutination Inhibition (HI) test. The serum antibody titers (ND) of group B and C on days 7 and 21 were higher than the other groups (P<0.05), but the difference between the other groups was not significant on the same day. The serum antibody titers (ND) of broiler chickens in group B and C on day 7, 21 and also group E on day 21 were significantly higher than other groups. The serum antibody titers (AI) of SPF chickens on day 21, in group C, had significant difference with other groups. The antibody titers (AI) on days 7 and 14 showed no significant difference in all groups except group D. The immunogenicity of emulsions was higher in more homogenization time. In all, these results indicate that increases in homogenization time create a smaller size of droplets and are effective for the rapid onset of antibody production. The small size of droplets not only creates a fast and good response, but also promotes immunogenicity both in broilers and SPF chickens. [ABSTRACT FROM AUTHOR]

Background: We aimed to evaluate the efficacy, safety, and immunogenicity of a SARS-CoV-2 mRNA vaccine (Omicron BA.5) LVRNA012 given as the booster in immunized but SARS-CoV-2 infection-free adults in China. Methods: This is a single-center, randomized, double-blind, placebo-controlled phase 3 clinical trial enrolling healthy adult participants (≥18 years) who had completed two or three doses of inactivated COVID-19 vaccines at least 6 months before, in Bengbu, Anhui province, China. Eligible participants were randomly assigned (1:1) to receive a booster intramuscular vaccination with an LVRNA012 vaccine (100ug) or placebo. The primary endpoint was the protective efficacyof a boosterdose of the LVRNA012vaccineor placeboagainst symptomatic COVID-19 of any severity 14 days after vaccination. Laboratory-confirmed COVID- 19 infections were identified from14 days to 180 days after intervention, with active surveillance for symptomatic illness 8 times permonth between 7 to 90 days and at least once per month between 90 to 180 days after intervention. Results: 2615 participants were recruited and randomly assigned in a 1:1 ratio to either the vaccine group (1308) or the placebo group (1307). A total of 141 individuals (46 in the LVRNA012 group and 95 in the placebo group) developed symptomatic COVID-19 infection 14 days after the booster immunization, showing a vaccine efficacy of 51.9% (95% CI, 31.3% to 66.4%). Most infections were detected 90 days after intervention during a period when XBB was prevalent in the community. Adverse reactions were reported by 64% of participants after the LVRNA012 vaccination, but most of them were mild or moderate. The booster vaccination with the LVRNA012 mRNA vaccine could significantly enhance neutralizing antibody titers against the Omicron variant XBB.1.5 (GMT 132.3 99.8, 175.4]) than did those in the placebo group (GMT 12.5 [8.4, 18.7]) at day 14 for the previously immunized individuals. Conclusion: The LVRNA012 mRNA vaccine is immunogenic, and shows robust efficacy in preventing COVID-19 during the omicron-predominate period. Clinical trial registration: ClinicalTrials.gov, identifier NCT05745545. [ABSTRACT FROM AUTHOR]

Objective: The mRNA SARS-CoV-2 vaccine has been shown to have no adverse effects on semen parameters. However, it is yet unknown whether the inactivated vaccinations have the same effect. Thus, our objective was to evaluate the parameters of sperm prior and following the administration of mRNA and inactivated COVID-19 vaccinations. Methods: In this study, the sperm quality was evaluated both before and after receiving the COVID-19 mRNA and inactivated vaccines. Of the participants, 28 received two doses of CoronaVac vaccine and 152 received two doses of mRNA BNT162b2 mRNA vaccine (Pfizer-BioNTech). Semen analyses were repeated 72 (57-145) days after the same individuals had received their second dose of COVID-19 vaccination. Results: No significant differences were found in the parameters of sperm before and after administration of two doses of BNT162b2 vaccine. Prior to and following administration of the two doses of the inactivated vaccine, there was no appreciable variation in the volume of semen, sperm concentration, progressive motility, total motility, immotility, or morphologically normal sperm features. Following CoronaVac vaccination before and after two doses, only the total sperm count was shown to statistically decrease (p=0.03). Conclusion: As a result, while there was no significant difference in the sperm parameters of the mRNA vaccine, it was determined that there was a statistical decrease in the total sperm count before and after two doses of CoronaVac vaccine. Since the semen volume of all patients is within normal limits, the first issue to be used here as a number is sperm per ml, which is important in terms of infertility, is the number. [ABSTRACT FROM AUTHOR]

Various vaccine platforms have been approved for broad use to prevent the transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. However, these vaccines exhibit distinct differences in immunogenicity and efficacy, which decline after vaccination and are further exacerbated by the emergence of virus variants and mutants. This study reports the immunization outcomes against the SARS-CoV-2 virus by assessing the immune responses and safety of different SARS-CoV-2 vaccines co-administered in BALB/c mice. Vaccine combinations comprising mRNA/adenovirus26-vector, mRNA/inactivated, adenovirus26-vector/inactivated, and mRNA/adenovirus26-vector/inactivated vaccines were prepared in optimized doses, and their activities upon immunization evaluated in comparison with individual mRNA, adenovirus26-vectored, and inactivated vaccines. Fourteen- and 28-days post-immunization, we measured spike-specific IgG response using Enzyme-Linked Immunosorbent Assay (ELISA), cytokine expression profiles through Quantitative real-time polymerase chain reaction (RT-PCR), and evaluated safety through histopathological examination. The mRNA/Vector/Inactivated group exhibited slightly higher anti-spike IgG levels, albeit not statistically significant (p > 0.132). Importantly, this regimen induced elevated IL-6 and IFN-γ mRNA expression levels (p < 0.0001) compared to immunization with individual vaccines. In summary, this study demonstrated that co-administering the mRNA/adenovirus26 vector/inactivated SARS-CoV-2 vaccines improved spike-specific IgG response, triggered significantly enhanced IL-6 and IFN-γ mRNA expression levels, and proved safe in mice. [ABSTRACT FROM AUTHOR]

This study longitudinally evaluated the immune response in individuals over a year after receiving three doses of an inactivated SARS‐CoV‐2 vaccine, focusing on reactions to Omicron breakthrough infections. From 63 blood samples of 37 subjects, results showed that the third booster enhanced the antibody response against Alpha, Beta, and Delta VOCs but was less effective against Omicron. Although antibody titres decreased post‐vaccination, SARS‐CoV‐2‐specific T‐cell responses, both CD4+ and CD8+, remained stable. Omicron breakthrough infections significantly improved neutralization against various VOCs, including Omicron. However, the boost in antibodies against WT, Alpha, Beta, and Delta variants was more pronounced. Regarding T cells, breakthrough infection predominantly boosted the CD8+ T‐cell response, and the intensity of the spike protein‐specific T‐cell response was roughly comparable between WT and Omicron BA.5. [ABSTRACT FROM AUTHOR]

An outbreak of camelpox occurred in the Mangistau region of Kazakhstan in 2019. To control the outbreak of camelpox and to prevent its further spread to other regions, camels were vaccinated using live and inactivated camelpox vaccines produced in Kazakhstan. To evaluate the efficacy of these camelpox vaccines in the field, vaccine trials used 172 camels on camel farms in the Beineu district. Of these, 132 camels were vaccinated using a live attenuated camelpox vaccine and 40 camels were vaccinated using an inactivated vaccine to observe immunogenicity and safety. The live vaccine was inoculated into camels by scarification at a dose of 5 × 104 EID50, and the inactivated vaccine was injected intramuscularly at 5 mL twice, with an interval of 35 days. During the safety evaluation, camels administered either vaccine displayed no clinical signs of illness or any adverse effects. Post-vaccination seroconversion demonstrated that the live attenuated vaccine started to elicit antibody responses in some animals as early as day seven, while, by day 28, 99% of vaccinated camels responded. For camels immunized with the inactivated vaccine, seroconversion began on day 21 at low titers ranging from 1:2 to 1:4. Ninety days post vaccination, 77% of the camels demonstrated an immune response that was up to a titer of 1:16. The antibody response waned six months post vaccination in camels vaccinated with two types of vaccine. Nonetheless, both vaccines were 100% effective at preventing clinical disease in vaccinated camels during the camelpox outbreak. All unvaccinated camels became ill, with manifestations of clinical signs characteristic of camelpox. Following these successful field trials in Kazakhstan, a vaccination program for camels, to control camelpox using the domestically produced live attenuated camelpox vaccine, has started. [ABSTRACT FROM AUTHOR]

ABSTRACT It remains unclear how previous infections and vaccinations influenced and shaped heterogeneous immune responses against Omicron and its variants in diverse populations in China. After the national wave of Omicron in early 2023, we evaluated serum levels of neutralizing antibodies (nAbs) against Omicron (B.1.1.529) and its variants (BA.5, BF.7, and CH1.1) in 33 COVID-19 convalescents and 40 uninfected vaccinees, using vesicular stomatitis virus-based pseudovirus neutralizing assay. In addition, we followed 34 Delta convalescent patients to compare their immune responses against Omicron before (late 2021) and after the Omicron wave (early 2023). NAbs at the acute phase of the disease were investigated in 50 Omicron inpatients, including 24 vaccinated and 26 unvaccinated patients. Among them, nasal mucosal IgA levels were measured in 42 subjects. Compared to vaccination, breakthrough infections significantly increased the breadth and magnitude of serum nAbs and mucosal IgA levels against Omicron variants. Exposure to Omicron but not Delta elicited stronger pan-Omicron responses. In Omicron inpatients, nAbs continued to rise as vaccination doses increased. However, in both vaccinees and convalescents, a fourth dose vaccination did not elicit higher nAbs against Omicron. Furthermore, nAbs against Omicron variants lasted longer than nAbs against WT SARS-CoV-2. Breakthrough infections of Omicron variants elicited specific immune responses against Omicron compared to vaccination and Delta infection. Although repeated vaccination revealed limited impacts on serum nAbs, populations at high risk of hospitalization may still benefit from continued vaccination.IMPORTANCEThe study described the specific humoral immunity against Omicron and its variants (BA.5, BF.7, and CH1.1) in diverse populations, including Delta-positive convalescent patients, Omicron-infected patients with a previous or current confirmed Delta infection, Omicron-positive patients, and healthy controls. In addition, we followed Delta convalescents for 1 year to evaluate the effect of a booster vaccine, breakthrough infection, and reinfection. Nasal mucosal IgA levels against SARS-CoV-2 were also examined. The findings of this study demonstrated the varied responses of individuals in different states following the outbreak of Omicron, highlighting the potential advantages of ongoing immunization for groups that are more vulnerable and have a greater likelihood of being hospitalized.

Abstract Bordetella bronchiseptica (Bb) is recognized as a leading cause of respiratory diseases in dogs and cats. However, epidemiological data on Bb in dogs and cats in China are still limited, and there is no commercially available vaccine. Live vaccines containing Bb that are widely used abroad are generally effective but can establish latency and potentially reactivate to cause illness in some immunodeficient vaccinated recipients, raising safety concerns. In this study, 34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023. The PCR results showed that the percentage of positive Bb was 22.94% (441/1922), and more than 90% of the Bb isolates had four virulence factor-encoding genes (VFGs), namely, fhaB, prn, betA and dnt. All the isolated strains displayed a multidrug-resistant phenotype. The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice, and we found that eight isolates were highly virulent. Furthermore, the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice, and three Bb strains (WH1218, WH1203 and WH1224) with the best protective efficacy were selected. Dogs immunized with these three strains exhibited strong protection against challenge with the Bb field strain WH1218. Ultimately, the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate. Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb field strain WH1218. This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China, and all the isolates exhibited multidrug resistance. The present work contributes to the current understanding of the prevalence, antimicrobial resistance, and virulence genes of Bb in domestic dogs and cats. Additionally, our results suggest that the WH1218 strain is a promising candidate safe and efficacious inactivated Bb vaccine.

ObjectiveTo determine the serum antibody level and risk factors in the adolescent population in a county in Zhejiang Province， following the immunization with inactivated COVID-19 vaccine， and to construct a prediction model for antibody concentration.MethodsWe conducted the study in a county in Zhejiang Province， employing a stratified cluster random sampling strategy in school children who had received the inactivated COVID-19 vaccine. Data on gender， age， type of vaccine， and time of vaccination was collected. Serum samples were also collected to test for anti-S and N IgG antibody against the SARS-CoV-2 by using chemiluminescent immunoassay （CLIA）. Risk factors were determined to construct a prediction model for antibody concentration.ResultsThe IgG antibody concentration was significantly higher in girls， those who received two doses， and those who had simply received the KX vaccine . It decreased with age and time interval between the sampling and last vaccination. The prediction model constructed by random forest regression in the study had a better model fit and predictive ability than that by the multivariable linear stepwise regression.ConclusionGender， age， vaccination dose， type of vaccine， and time of vaccination are associated with vaccination effectiveness of inactivated COVID-19 vaccines in adolescents. Prediction model could predict the antibody level in the vaccinated population， which can provide a new tool for better evaluation of vaccination effectiveness against emerging infectious diseases in future.

ObjectiveTo illustrate the mechanism of COVID-19 vaccine in the T cell immune response.MethodsBased on the characteristics of T cell and B cell immune response， we matched the data of incubation periods across the SARS-CoV-2 prototype strain， Delta variants， and Omicron variants and effectiveness of mRNA and inactivated COVID-19 vaccines for analysis.ResultsThe effectiveness of mRNA COVID-19 vaccine against infection and onset was consistent with incubation period principally being ≥5 days. In contrast， the effectiveness of inactivated COVID-19 vaccine was consistent with incubation period principally being ≥8 days.ConclusionIt may be interpreted by faster T cell immune response stimulated by mRNA vaccine， compared to B cell immune response by inactivated vaccine.

Toxoplasma gondii is a ubiquitous parasite causing significant mortality in captive wildlife, especially marsupials. Historically, treatment has been unrewarding and no vaccine was available. An intranasal vaccine based on purified inactivated T. gondii was developed for toxoplasmosis prevention. A vaccination campaign started in early 2017 and was successful in preventing toxoplasma-related mortality in marsupials in many European and South American zoos. Amongst the vaccinated wallabies, about 30% were T. gondii seropositive before the vaccination, and no toxoplasma-related deaths were observed since the administration of the vaccine. The objective of this case study was to assess the potential effect of the vaccination on a seropositive wallaby. It is important to note that this vaccine doesn't induce any humoral response in sheep, and squirrel monkeys but induces a strong T-cell response. A T. gondii seropositive Yellow-footed rock wallaby (Petrogale xanthopus) from Copenhagen Zoo received two doses of the aforementioned intranasal vaccine. Blood samples were collected before each vaccination and used for peripheral blood mononuclear cell isolation. The impact of the vaccination on the lymphocyte phenotype was characterized by flow cytometry. Cell size, represented by forward scatter, and granularity, represented by side scatter parameters were analyzed. Two doses of the vaccine induced a respective 30.1 and 25.6% increase in cell size and granularity in lymphocytes stimulated with T. gondii antigens, as assessed by flow cytometry. These changes were likely correlated with T-cell activation, which indicates that two doses of the vaccine might have boosted the already-existing T-cell memory response against T. gondii in a seropositive animal. No morphological changes were observed in lymphocytes from an unvaccinated seronegative wallaby. This is the first documented case of boosting an already-existing cellular immune response against toxoplasmosis by the vaccine in a seropositive Yellow-footed rock wallaby.

ABSTRACTCoxsackievirus B4 (CVB4) is associated with a range of acute and chronic diseases such as hand, foot, and mouth disease, myocarditis, meningitis, pancreatitis, and type 1 diabetes, affecting millions of young children annually around the world. However, no vaccine is currently available for preventing CVB4 infection. Here, we report the development of inactivated viral particle vaccines for CVB4. Two types of inactivated CVB4 particles were prepared from CVB4-infected cell cultures as vaccine antigens, including F-particle (also called mature virion) consisting of VP1, VP3, VP2, and VP4 subunit proteins, and E-particle (also called empty capsid) which is made of VP1, VP3, and uncleaved VP0. Both the inactivated CVB4 F-particle and E-particle were able to potently elicit neutralizing antibodies in mice, despite slightly lower neutralizing antibody titres seen with the E-particle vaccine after the third immunization. Importantly, we demonstrated that passive transfer of either anti-F-particle or anti-E-particle sera could completely protect the recipient mice from lethal CVB4 challenge. Our study not only defines the immunogenicity and protective efficacy of inactivated CVB4 F-particle and E-particle but also reveals the central role of neutralizing antibodies in anti-CVB4 protective immunity, thus providing important information that may accelerate the development of inactivated CVB4 vaccines.

Bordetella bronchiseptica (Bb) is recognized as a leading cause of respiratory diseases in dogs and cats. However, epidemiological data on Bb in dogs and cats in China are still limited, and there is no commercially available vaccine. Live vaccines containing Bb that are widely used abroad are generally effective but can establish latency and potentially reactivate to cause illness in some immunodeficient vaccinated recipients, raising safety concerns. In this study, 34 canine-derived and two feline-derived Bb strains were isolated from 1809 canine and 113 feline nasopharyngeal swab samples collected from eight provinces in China from 2021 to 2023. The PCR results showed that the percentage of positive Bb was 22.94% (441/1922), and more than 90% of the Bb isolates had four virulence factor-encoding genes (VFGs), namely, fhaB, prn, betA and dnt. All the isolated strains displayed a multidrug-resistant phenotype. The virulence of 10 Bb strains isolated from dogs with respiratory symptoms was tested in mice, and we found that eight isolates were highly virulent. Furthermore, the eight Bb isolates with high virulence were inactivated and intramuscularly injected into mice, and three Bb strains (WH1218, WH1203 and WH1224) with the best protective efficacy were selected. Dogs immunized with these three strains exhibited strong protection against challenge with the Bb field strain WH1218. Ultimately, the WH1218 strain with the greatest protection in dogs was selected as the vaccine candidate. Dogs and cats that received a vaccine containing 109 CFU of the inactivated WH1218 strain showed complete protection against challenge with the Bb field strain WH1218. This study revealed that Bb is an important pathogen that causes respiratory diseases in domestic dogs and cats in China, and all the isolates exhibited multidrug resistance. The present work contributes to the current understanding of the prevalence, antimicrobial resistance, and virulence genes of Bb in domestic dogs and cats. Additionally, our results suggest that the WH1218 strain is a promising candidate safe and efficacious inactivated Bb vaccine. [ABSTRACT FROM AUTHOR]

Porcine idiopathic vesicular disease (PIVD), one of several clinically indistinguishable vesicular diseases of pigs, is caused by the emerging pathogen Senecavirus A (SVA). Despite the widespread prevalence of porcine SVA infection, no effective commercial vaccines for PIVD prevention and control are available, due to high costs associated with vaccine testing in pigs, considerable SVA diversity, and SVA rapid evolution. In this study, SVA CH/JL/2022 (OP562896), a novel mutant SVA strain derived from an isolate obtained from a pig farm in Jilin Province, China, was inactivated then combined with four adjuvants, MONTANIDETM GEL02 PR (GEL 02), MONTANIDETM ISA 201 VG (ISA 201), MONTANIDETM IMG 1313 VG N (IMS1313), or Rehydragel LV (LV). The resulting inactivated SVA CH/JL/2022 vaccines were assessed for efficacy in mice and found to induce robust in vivo lymphocyte proliferation responses and strong IgG1, IgG2a, and neutralizing antibody responses with IgG2a/IgG1 ratios of <1. Furthermore, all vaccinated groups exhibited significantly higher levels of serum cytokines IL-2, IL-4, IL-6, and IFN as compared to unvaccinated mice. These results indicate that all vaccines elicited both Th1 and Th2 responses, with Th2 responses predominating. Moreover, vaccinated mice exhibited enhanced resistance to SVA infection, as evidenced by reduced viral RNA levels and SVA infection-induced histopathological changes. Collectively, our results demonstrate that the SVA-GEL vaccine induced more robust immunological responses in mice than did the other three vaccines, thus highlighting the potential of SVA-GEL to serve an effective tool for preventing and controlling SVA infection. [ABSTRACT FROM AUTHOR]

Background and objectives: Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction. No cohort study has investigated the efficacy of inactivated vaccines in patients with MG. Materials and methods: This prospective observational cohort study included healthy controls (HCs) and patients with MG with or without immunosuppressive treatment. Vaccination occurred between May and December 2021. Patients with MG were subjected to a clinical scale assessment for disease severity. The neutralization antibodies (Nabs) levels were measured in all participants using the pseudovirus neutralization assay. Results: Twenty-one patients (Female/Male:10/11); age median [interquartile range (IQR)]: 43 [30, 56]) were included in this study. Two patients (2/21) were lost during follow-up after enrollment. No sustained vaccine-related adverse effects occurred in any visit of patients with MG. No exacerbation of MG was observed. Acetylcholine receptor antibody (AChR-Ab) levels showed no statistically significant changes between the first and second visit (median [IQR]: 2.22 [0.99, 2.63] nmol/L vs. 1.54 [1.07, 2.40] nmol/L, p = 0.424). However, levels of AChR-Ab decreased at the third visit (median [IQR]: 2.22 [0.96, 2.70] nmol/L vs. 1.69 [0.70, 1.85] nmol/L, p = 0.011). No statistically significant difference in Nabs levels was found between HCs and patients with MG (median [IQR]: 102.89 [33.13, 293.86] vs. 79.29 [37.50, 141.93], p = 0.147). Discussion: The safety of the SARS-CoV-2 inactivated vaccine was reconfirmed in this study. No significant difference in Nabs level was found between patients with MG and HCs. Nabs levels correlated with AChR-Ab levels before vaccination and ΔAChR-Ab levels. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the immunogenicity and safety of different types of poliovirus vaccines. Methods: A randomized, blinded, single-center, parallel-controlled design was employed, and 360 infants aged ≥ 2 months were selected as study subjects. They were randomly assigned to bOPV group (oral Sabin vaccine) and sIPV group (Sabin strain inactivated polio vaccine), with 180 infants in each group. Adverse reaction events in the vaccinated subjects were recorded. The micro-neutralization test using cell culture was conducted to determine the geometric mean titer (GMT) of neutralizing antibodies against poliovirus types I, II, and III in different groups, and the seroconversion rates were calculated. Results: Both groups exhibited a 100% seropositivity rate after booster immunization. The titers of neutralizing antibodies for the three types were predominantly distributed within the range of 1:128 to 1:512. The fold increase of type I antibodies differed markedly between the two groups (P < 0.05). Moreover, the fold increase of type II and type III antibodies for poliovirus differed slightly between the two groups (P > 0.05). The fourfold increase rate in sIPV group was drastically superior to that in bOPV group (P < 0.05). When comparing the post-immunization GMT levels of type I antibodies in individuals who completed the full course of spinal muscular atrophy vaccination, bOPV group showed greatly inferior levels to sIPV group (P < 0.05). For type II and type III antibodies, individuals in bOPV group demonstrated drastically superior post-immunization GMT levels to those in sIPV group (P < 0.05). The incidence of adverse reactions between the bOPV and sIPV groups differed slightly (P > 0.05). Conclusion: These findings indicated that both the oral vaccine and inactivated vaccine had good safety and immunogenicity in infants aged ≥ 2 months. The sIPV group generated higher levels of neutralizing antibodies in serum, particularly evident in the post-immunization GMT levels for types II and III. [ABSTRACT FROM AUTHOR]

Uncovering the immune response to an inactivated SARS‐CoV‐2 vaccine (In‐Vac) and natural infection is crucial for comprehending COVID‐19 immunology. Here we conducted an integrated analysis of single‐cell RNA sequencing (scRNA‐seq) data from serial peripheral blood mononuclear cell (PBMC) samples derived from 12 individuals receiving In‐Vac compared with those from COVID‐19 patients. Our study reveals that In‐Vac induces subtle immunological changes in PBMC, including cell proportions and transcriptomes, compared with profound changes for natural infection. In‐Vac modestly upregulates IFN‐α but downregulates NF‐κB pathways, while natural infection triggers hyperactive IFN‐α and NF‐κB pathways. Both In‐Vac and natural infection alter T/B cell receptor repertoires, but COVID‐19 has more significant change in preferential VJ gene, indicating a vigorous immune response. Our study reveals distinct patterns of cellular communications, including a selective activation of IL‐15RA/IL‐15 receptor pathway after In‐Vac boost, suggesting its potential role in enhancing In‐Vac‐induced immunity. Collectively, our study illuminates multifaceted immune responses to In‐Vac and natural infection, providing insights for optimizing SARS‐CoV‐2 vaccine efficacy. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a life-threatening viral zoonosis. The causative agent of this disease is the Dabie bandavirus, which is usually known as the SFTS virus (SFTSV). Although the role of vertebrates in SFTSV transmission to humans remains uncertain, some reports have suggested that dogs could potentially transmit SFTSV to humans. Consequently, preventive measures against SFTSV in dogs are urgently needed. In the present study, dogs were immunized three times at two-week intervals with formaldehyde-inactivated SFTSV with two types of adjuvants. SFTSV (KCD46) was injected into all dogs two weeks after the final immunization. Control dogs showed viremia from 2 to 4 days post infection (dpi), and displayed white pulp atrophy in the spleen, along with a high level of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling assay (TUNEL) positive area. However, the inactivated SFTSV vaccine groups exhibited rare pathological changes and significantly reduced TUNEL positive areas in the spleen. Furthermore, SFTSV viral loads were not detected at any of the tested dpi. Our results indicate that both adjuvants can be safely used in combination with an inactivated SFTSV formulation to induce strong neutralizing antibodies. Inactivated SFTSV vaccines effectively prevent pathogenicity and viremia in dogs infected with SFTSV. In conclusion, our study highlighted the potential of inactivated SFTSV vaccination for SFTSV control in dogs. [ABSTRACT FROM AUTHOR]

Background: Despite the widespread adoption of COVID-19 vaccination, a comprehensive understanding of potential vaccine-induced adverse effects, particularly in the context of pregnancy, remains a critical area of investigation. Elevated concerns surround the maternal and neonatal outcomes subsequent to prenatal maternal COVID-19 vaccination. While existing studies have provided insights into the safety profile of COVID-19 mRNA vaccines, the extrapolation of these conclusions to inactivated COVID-19 vaccines poses uncertainties. Notably, limited data are available regarding the maternal and neonatal effects associated with inactivated COVID-19 vaccines. Objective: To evaluate the prenatal maternal inactivated COVID-19 vaccination and the impact on maternal and neonatal outcomes. Methods: This was a retrospective cohort study of women who delivered between January and June 2022 at a single university-affiliated hospital. Those who have completed at least one dose of inactivated vaccine before or during pregnancy were included in "vaccinated group," and those who were not vaccinated were included in "unvaccinated group," the maternal, pregnancy and neonatal outcomes were evaluated. Propensity score matching (PSM) was performed to balance the baseline parameters of the two groups. Results: A total of 1926 women were enrolled in this study, 827 (42.94%) women were prenatally vaccinated, and 1099 (57.06%) unvaccinated. The gestational week of delivery were slightly lower in the vaccinated group, 38.61 ± 1.89 weeks in the vaccinated group and 38.93 ± 1.49 weeks in the unvaccinated group. There was a higher rate of overall preterm delivery in the vaccinated group (aOR 1.61, 95% CI 1.07-2.42; p = 0.02), however, the probability of delivery before 34 weeks and before 32 weeks (early preterm delivery) were similar (p > 0.05). A total of 2009 infants were born, 851 in the vaccinated group and 1158 in the unvaccinated group. There were similar neonatal outcomes in the two groups. Conclusion: Although we found a slightly lower gestational week of delivery and a possible increased rate of late preterm birth in the vaccination group, there was no difference in mean neonatal weight, incidence of low birth weight infants and other neonatal adverse complications. Meanwhile, there was no difference in pregnancy and maternal outcomes between the two groups. [ABSTRACT FROM AUTHOR]

Dengue, caused by the dengue virus (DENV), affects millions of people worldwide every year. This virus has two distinct life cycles, one in the human and another in the mosquito, and both cycles are crucial to be controlled. To control the vector of DENV, the mosquito Aedes aegypti, scientists employed many techniques, which were later proved ineffective and harmful in many ways. Consequently, the attention shifted to the development of a vaccine; researchers have targeted the E protein, a surface protein of the virus and the NS1 protein, an extracellular protein. There are several types of vaccines developed so far, such as live attenuated vaccines, recombinant subunit vaccines, inactivated virus vaccines, viral vectored vaccines, DNA vaccines, and mRNA vaccines. Along with these, scientists are exploring new strategies of developing improved version of the vaccine by employing recombinant DNA plasmid against NS1 and also aiming to prevent the infection by blocking the DENV life cycle inside the mosquitoes. Here, we discussed the aspects of research in the field of vaccines until now and identified some prospects for future vaccine developments. [ABSTRACT FROM AUTHOR]

Context: Feedlot entry can be a period of stress for cattle due to transportation, altered diets and other influences. Stress can suppress host defence mechanisms. Innate immune stimulants, such as mycobacterial cell-wall fractions, attract attention for the primary objective of enhancing non-specific immune resistance of cattle against microbial diseases during periods of stress-induced susceptibility. These stimulants are also recognised for their capacity to modify responses of the adaptive immune system to vaccines. Aims: This study aims to evaluate the potential for mycobacterial cell-wall fractions in Amplimune® to modify adaptive immune responses to the commercial vaccines Rhinogard® (modified live bovine alphaherpesvirus-1 (BoHV-1)) and Bovilis MH + IBR® (inactivated Mannheimia haemolytica and BoHV-1) in yearling cattle during simulated feedlot induction. Methods: Fifty-four mixed-sex Angus yearling cattle were transported for 6 h on Day −1 and on Day 0. The cattle were assigned to the following six treatment groups (n = 9/group): Rhinogard plus 2 mL Amplimune, Rhinogard plus 5 mL Amplimune, Bovilis MH + IBR plus 2 mL Amplimune, Bovilis MH + IBR plus 5 mL Amplimune, Rhinogard plus 5 mL saline, and Bovilis MH + IBR plus 5 mL saline. Blood and nasal secretions were sampled at various time points following treatment and antigen-specific antibody (immunoglobulin G) responses to components of the vaccines were assessed. Interferon-γ production by peripheral blood mononuclear cells in response to BoHV-1, Concanavalin A or media only were assessed. Key results: No adverse clinical reactions were observed to administration of Amplimune and vaccines. A systemic antibody response to vaccination was observed for the Bovilis MH + IBR vaccine. Vaccine-specific antibody and cytokine responses were not modified by Amplimune. Conclusions: Amplimune can be administered at the same time as Rhinogard or Bovilis MH + IBR vaccines, without undesirable effects on specific immune responses to vaccination. Implications: The primary interest in using Amplimune is to potentiate non-specific immune defences as an alternative to antibiotics for the prevention and/or treatment of microbial diseases such as bovine respiratory disease in production animals. In view of its adjuvant-like activities, administration of Amplimune might also confer beneficial or detrimental effects on antigen-specific responses of the adaptive immune system to contemporaneous vaccination. Most vaccines do not confer immediate protection in the host; however, concurrent administration of immune stimulants may enhance or impair immune responses to those vaccines. Bovine respiratory disease (BRD) is costly for Australian cattle and, in this trial, concurrent vaccination against BRD with the stimulant Amplimune was investigated and found to have no detrimental effect on immune responses. These findings warrant further examination of the effect of Amplimune on morbidities and mortalities in feedlots. [ABSTRACT FROM AUTHOR]

Rabies is a zoonotic disease with high lethality. Most human deaths are associated with the bites received from dogs and cats. Vaccination is the most effective method of preventing rabies disease in both animals and humans. In this study, the ability of an adjuvant based on recombinant Salmonella typhimurium flagellin to increase protective activity of the inactivated rabies vaccine in mice was evaluated. A series of inactivated dry culture vaccine for dogs and cats "Rabikan" (strain Shchelkovo-51) with addition of an adjuvant at various dilutions were used. The control preparation was a similar series of inactivated dry culture vaccine without an adjuvant. Protective activity of the vaccine preparations was evaluated by the NIH potency test, which is the most widely used and internationally recommended method for testing effectiveness of the inactivated rabies vaccines. The value of specific activity of the tested rabies vaccine when co-administered with the adjuvant was significantly higher (48.69 IU/ml) than that of the vaccine without the adjuvant (3.75 IU/ml). Thus, recombinant flagellin could be considered as an effective adjuvant in the composition of future vaccine preparations against rabies virus. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19 vaccination is considered a primary preventive measure to combat the COVID-19 pandemic. Several types of COVID-19 vaccines were developed, among them the mRNA-based vaccine and the inactivated virus vaccine. Different COVID-19 vaccines have different purchase price and require different logistics system, which translate into different estimated vaccination costs. Therefore, this study aims to estimate the cost of COVID-19 vaccination using the mRNA-based vaccine compared to the inactivated virus vaccine to assist future decision-making related to COVID-19 vaccination. Methods: Direct costs for per-dose vaccination for both vaccines were estimated from the health provider's perspective using the microcosting approach. Vaccination pathways were constructed for both the mRNA-based and the inactivated virus vaccine based on activities involving the acquisition, transportation, storage, and vaccine injection processes. Cost value was obtained from purchase documents, asset records, and market surveys. Results: The estimated costs for COVID-19 vaccination were RM 69.71 per dose for the mRNA-based vaccine and RM 91.68 per dose for the inactivated virus vaccine. The difference in estimated vaccination costs was mainly driven by the difference in the vaccine purchase costs which was higher for the inactivated virus vaccine. Conclusion: COVID-19 vaccination using the mRNA-based vaccine incur was estimated to incur lower total costs to the health provider compared to the inactivated virus vaccine during the pandemic. [ABSTRACT FROM AUTHOR]

This article presents the findings of a survey conducted in India on adverse events following COVID-19 vaccination. The study found that the majority of participants experienced adverse events, with pain at the injection site, general unwell feeling, and fever/chills being the most commonly reported effects. The study concluded that these adverse events were mostly mild and that both viral vector and inactivated vaccines were safe. The article suggests the need for increased public awareness of adverse event reporting to improve vaccine coverage. [Extracted from the article]

Objective: This study investigates the effectiveness of the 1st booster dose against COVID-19 severe and critical hospitalizations and deaths occurring due to the Omicron wave in Morocco. Participants/methods: This study uses nationally representative data on COVID-19 from 15 December 2021 to 31 January 2022. The aim is to investigate the effectiveness of the inactivated COVID-19 vaccine BBIBP-CorV (Sinopharm) 1st booster dose against the Omicron wave in Morocco using real-world data established from nationally representative statistics on COVID-19 cases, deaths and vaccinations. Statistical Analyses: The screening method was used to estimate vaccine effectiveness against COVID-19 severe or critical hospitalization and COVID-19-related deaths. The data were grouped by, age subgroup, sex, week, and geographical area and were analyzed using binary logistic regression with an offset for vaccine coverage. Results: The overall BBIBP-CorV VE estimate is 89% (95% CI 85 to 92) effective in curbing COVID-19 deaths, and 81% (95% CI 78 to 84 in curbing COVID-19 severe/critical hospitalizations. Death-related VE estimate was 86% (95% CI 81 to 90) for patients aged ≥65 years, 96% (95% CI 90 to 98) for those aged <65 years, 95% (95% CI 88 to 98) in no-risk factor patients, 91% (95% CI 85 to 94) with 1 risk factor, 90% (95% CI 83 to 95) with 2 risk factors, and 72% (95% CI 52 to 84) in patients with 3 risk factors and more. Severe/critical hospitalization VE estimate was 78% (95% CI 74 to 82) for patients aged ≥65 years, 87% (95% CI 82 to 90) for those aged <65 years, 86% (95% CI 80 to 90) in no-risk factor patients, 80% (95% CI 73 to 84) with 1 risk factor, 80% (95% CI 70 to 85) with 2 risk factors, and 80% (95% CI 68 to 86) in patients with 3 risk factors and more. Conclusions: BBIBP-CorV boosters are effective in increasing protection against the Omicron variant-related COVID-19 deaths and severe/critical hospitalizations. The protection is reduced with older age and higher risk factors. These findings emphasize the importance of targeted vaccination strategies for different demographic groups and underscore the protective benefits of the first booster BBIBP-CorV vaccine. [ABSTRACT FROM AUTHOR]

COVID‐19 is a systemic inflammatory disease initiated by SARS‐CoV‐2 virus infection. Multiple vaccines against the Wuhan variant of SARS‐CoV‐2 have been developed including a whole virion beta‐propiolactone‐inactivated vaccine based on the B.1.1 strain (CoviVac). Since most of the population has been vaccinated by targeting the original or early variants of SARS‐CoV‐2, the emergence of novel mutant variants raises concern over possible evasion of vaccine‐induced immune responses. Here, we report on the mechanism of protection by CoviVac, a whole virion‐based vaccine, against the Omicron variant. CoviVac‐immunized K18‐hACE2 Tg mice were protected against both prototype B.1.1 and BA.1‐like (Omicron) variants. Subsequently, vaccinated K18‐hACE2 Tg mice rapidly cleared the infection via cross‐reactive T‐cell responses and cross‐reactive, non‐neutralizing antibodies recognizing the Omicron variant Spike protein. Thus, our data indicate that efficient protection from SARS‐CoV‐2 variants can be achieved by the orchestrated action of cross‐reactive T cells and non‐neutralizing antibodies. [ABSTRACT FROM AUTHOR]

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The infectious bursal disease virus (IBDV) is severe and highly contagious, causing high mortality and immunosuppression in chickens worldwide. A new novel variant, IBDV (nVarIBDV), has recently emerged in Asian countries, including Malaysia, highlighting the need to develop a new vaccine against this strain due to the inadequacy of existing commercial vaccines in protecting chickens from nVarIBDV infection. Therefore, the current study aimed to evaluate the efficacy and safety of inactivated nVarIBDV as a potential vaccine candidate in broiler chickens. A total of 65 one-day-old Arbo Acres broiler chickens were randomly divided into three groups (five animals in each group with four replications) before the challenge, namely A, B, and C. Groups A and B were immunized subcutaneously at day old with inactivated nVarIBDV (107 EID50/0.2 ml), and Group B was boosted at day 14. Group C was an unimmunized control. The experimental animals were divided into three subgroups and were challenged with pathogenic nVarIBDV (105 EID50/1.0ml) on day 28 post-inoculation through ocular and oral routes. The challenge sub-groups were named ACH, BCH, and CCH, respectively. The live body weight, bursa weight, and blood samples of the chickens were recorded. Gross lesions were examined, and samples of the bursa of Fabricius were collected from all the groups for histological evaluation. All the chickens appeared healthy and normal throughout the trial. Body weight increased in all groups without significant differences. The bursa weight and the bursa-to-body weight ratio of the booster group (Group B) were significantly higher than the non-booster and control groups. Gross lesions were not observed in the investigated groups. The challenged control group had higher bursa lesion scoring than the vaccinated groups. The IBDV antibody titer of challenged chickens in ACH, BCH, and CCH groups was higher than those of unchallenged groups A, B, and C at 35 days post-inoculation. The IBDV antibody titer of challenged chickens in group B was higher than challenged chickens in groups A and C (ACH and CCH). In conclusion, the inactivated nVarIBDV demonstrated safety and efficacy, with the booster Group (B) showing elevated humoral immune responses compared to the non-booster group. [ABSTRACT FROM AUTHOR]

Background: This retrospective analysis aims to investigate the clinical characteristics of students infected with the SARS-CoV-2 Omicron variant in three Beijing schools. Additionally, we explore the dynamic trends of nucleic acid cycle threshold values (Ct values) and serum antibody titers throughout the disease course. Methods: Demographic, clinical, nucleic acid Ct values, and antibody titer data were collected from cases in a COVID-19 cluster in Beijing Ditan Hospital, Capital Medical University, spanning from September 6 to October 1, 2022. Results: A total of 107 students infected with Omicron (BA.5.2 and BA.2.76) were identified across three schools. Primary clinical manifestations included fever and upper respiratory symptoms (85/107, 79.4 %), with the majority being classified as mild cases (96/107, 89.7 %). Notably, middle school students in the second school exhibited a higher peak body temperature compared to college students in the first and third schools (39.5 °C vs. 38.4 °C, adjusted P = 0.005; 39.5 °C vs. 38.6 °C, adjusted P = 0.002). Analysis of dynamic changes in Ct values revealed the lowest median Ct value in nasopharyngeal swabs on the third day of illness, reaching 35 after 9–11 days. Oropharyngeal swab nucleic acid median Ct value reached 35 approximately 3–5 days post-onset. Serum antibody detection showed continuous negativity of IgM antibody titers from days 1–10, while IgG antibody titers were positive on the first day and increased rapidly after one week. Conclusions: The three COVID-19 cluster school outbreaks primarily resulted from Omicron infections, with no severe or fatal cases observed. Clinically, the selection of different types of SARS-CoV-2 nucleic acid swabs for virus detection can be tailored based on the infection's course.

The mRNA vaccines (RVs) can reduce the severity and mortality of severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, almost only the inactivated vaccines (IVs) but no RVs had been used in mainland China until most recently, and the relaxing of its anti-pandemic strategies in December 2022 increased concerns about new outbreaks. In comparison, many of the citizens in Macao Special Administrative Region of China received three doses of IV (3IV) or RV (3RV), or 2 doses of IV plus one booster of RV (2IV+1RV). By the end of 2022, we recruited 147 participants with various vaccinations in Macao and detected antibodies (Abs) against the spike (S) protein and nucleocapsid (N) protein of the virus as well as neutralizing antibodies (NAb) in their serum. We observed that the level of anti-S Ab or NAb was similarly high with both 3RV and 2IV+1RV but lower with 3IV. In contrast, the level of anti-N Ab was the highest with 3IV like that in convalescents, intermediate with 2IV+1RV, and the lowest with 3RV. Whereas no significant differences in the basal levels of cytokines related to T-cell activation were observed among the various vaccination groups before and after the boosters. No vaccinees reported severe adverse events. Since Macao took one of the most stringent non-pharmaceutical interventions in the world, this study possesses much higher confidence in the vaccination results than many other studies from highly infected regions. Our findings suggest that the heterologous vaccination 2IV+1RV outperforms the homologous vaccinations 3IV and 3RV as it induces not only anti-S Ab (to the level as with 3RV) but also anti-N antibodies (via the IV). It combines the advantages of both RV (to block the viral entry) and IV (to also intervene the subsequent pathological processes such as intracellular viral replication and interference with the signal transduction and hence the biological functions of host cells). [ABSTRACT FROM AUTHOR]

Vaccine-induced immunity wanes over time and warrants booster doses. We investigated the long-term (32 weeks) immunogenicity and safety of a third, homologous, open-label booster dose of TURKOVAC, administered 12 weeks after completion of the primary series in a randomized, controlled, double-blind, phase 2 study. Forty-two participants included in the analysis were evaluated for neutralizing antibodies (NAbs) (with microneutralization (MNT50) and focus reduction (FRNT50) tests), SARS-CoV-2 S1 RBD (Spike S1 Receptor Binding Domain), and whole SARS-CoV-2 (with ELISA) IgGs on the day of booster injection and at weeks 1, 2, 4, 8, 16, 24, and 32 thereafter. Antibody titers increased significantly from week 1 and remained higher than the pre-booster titers until at least week 4 (week 8 for whole SARS-CoV-2) (p < 0.05 for all). Seroconversion (titers ≥ 4-fold compared with pre-immune status) persisted 16 weeks (MNT50: 6-fold; FRNT50: 5.4-fold) for NAbs and 32 weeks for S1 RBD (7.9-fold) and whole SARS-CoV-2 (9.4-fold) IgGs. Nine participants (20.9%) tested positive for SARS-CoV-2 RT-PCR between weeks 8 and 32 of booster vaccination; none of them were hospitalized or died. These findings suggest that boosting with TURKOVAC can provide effective protection against COVID-19 for at least 8 weeks and reduce the severity of the disease. [ABSTRACT FROM AUTHOR]

[Objectives]The aim of this experiment was to explore the effect of H9N2 subtype avian influenza virus attack on the respiratory system of SPF chicken immunized with H9 inactivated vaccine. [Methods]36 SPF chickens were selected and randomly divided into the control group(Con),the challenge group(Flu)and the immunization followed challenge group(Vac+Flu). Chickens were immunized with H9 inactivated vaccine at a dose of 0.4 mL per chicken, and after 3 weeks, they were challenged at a dose of 10~6 EID50 of virus. The swabs, serum, trachea, lung and other samples were collected. Hemagglutination inhibition(HI)antibody titer, the genomes copies of influenza virus M gene and the expression levels of immune related genes CD4,CD8,GATA3,T-bet,IL-4,IL-13,TNF-α,IFN-γ,Perforin,Granzyme,FasL,Fas were separately detected by HI assay, RT-PCR and quantitative PCR(qPCR). And the pathological changes and distribution of virus specific antigen NP protein of trachea and lung were individually observed by hematoxylin-eosin staining and immunohistochemistry. [Results]The results of HI assay showed that SPF chicken could produce high H9N2 AIV antibody titer after immunization. The results of immune protection test and RT-PCR showed that the virus shedding and the expression of influenza virus M gene in lung tissue could still be detected after SPF chickens were immunized with vaccine and followed by viral infection. The result of hematoxylin-eosin staining and immunohistochemistry showed that inoculating the H9N2 AIV inactivated vaccine significantly alleviated the pathological damage of trachea and lung and significantly reduced the viral load of trachea and lung. Quantitative PCR showed that inoculating the H9N2 AIV inactivated vaccine significantly up-regulated the secretion of Th1 and Th2 cytokines and promoted the expression of perforin/granzyme pathway related genes to enhance cytotoxicity in the lung. [Conclusions]Although chickens inoculated with H9N2 vaccine were infected with H9 virus, there was still a phenomenon of virus shedding. Their antiviral immune system was active and the viral load of main organs was reduced. It is recommended to carry out vaccination according to the influenza vaccine immunization procedure to improve the level of influenza prevention. [ABSTRACT FROM AUTHOR]

Background and Purpose: Liver injury after Covid‐19 vaccine has been described, although the incidence was not well established. We aimed to compare cumulative incidence of new onset liver test alteration after Covid‐19 vaccination, and to compare with an historical control of influenza vaccination. Methods: We conducted a retrospective cohort study which included adults who received at least one dose of Covid‐19 vaccine from January 1 to May 30, 2021 and a control group who received a single dose of influenza vaccine during 2019, in a tertiary medical center from Argentina. Results: We included 29 798 patients in Covid‐19 vaccine group and 24 605 in influenza vaccine group. Liver function tests were performed in 7833 (26.9%) in Covid‐19 vaccine group and 8459 (34.37%) in influenza vaccine group. Cumulative incidence at 90 days of new onset liver enzyme test alteration was 4.7 per 1000 (95% 4.0–5.5) for Covid‐19 group, and 5.1 per 1000 (95% 4.3–6.1) for the influenza vaccine group (p value = 0.489). Two patients in the Covid‐19 vaccine group developed immune mediated liver injury. Conclusions: We found no difference in liver test alteration between groups. These findings support the safety of Covid‐19 vaccines. While we have identified two cases that are consistent with immune mediated liver injury following COVID‐19 vaccination, we believe that the available data is insufficient to attribute them solely to the vaccination. [ABSTRACT FROM AUTHOR]