Inactivated Vaccine Research Articles

A case of uveitis associated with novel corona-virus inactivated vaccine engineered CHO cells: A case report

Rationale: The pathogenesis and course of recombinant Corona Virus Disease 2019 vaccine (CHO cell) associated uveitis is rarely seen in clinical practice, thus, it is difficult and time-consuming to diagnose. Patient concerns: An adult female patient suffered from binocular visual impairment after receiving the Corona Virus Disease 2019 vaccine. The patient was healthy and had no family history of retinal dystrophy previously. This case showed the following features in multimodal imaging including scattered speckled fluorescein leakage was seen around the optic disc, and the leakage was slightly enhanced in the later stage. The macular area showed about 4 papillary diameter size discoid retinal detachment area fluorescein pool staining. Optical coherence tomography showed retinal choroidal folds above the optic disc, a small amount of fluid under the neuroepithelial layer, and serous detachment of the neuroepithelial layer in the macular area. Diagnosis: Posterior uveitis of both eyes. Intervention: Orally Maizhiling, Ginkgo biloba leaves, and multivitamins. Outcome: After treatment, the symptoms of the patient were significantly improved, and optical coherence tomography reexamination showed exudation had been absorbed. Lessons: The injection of a novel coronavirus-inactivated vaccine (CHO cell) can lead to potential uveitis disorders, which is worthy of clinical attention, but the prognosis of patients is good.

Towards preliminary inactivated vaccine for SARS CoV-2 isolated from Egypt: ‎Isolation, propagation and inactivation of SARS CoV-2 Omicron variant (in vitro ‎study)‎

Towards preliminary inactivated vaccine for SARS CoV-2 isolated from Egypt: ‎Isolation, propagation and inactivation of SARS CoV-2 Omicron variant (in vitro ‎study)‎

Sex-Dependent Effects on Influenza-Specific Antibody Quantity and Neutralizing Activity following Vaccination of Newborn Non-Human Primates Is Determined by Adjuvants.

A number of studies have demonstrated the role of sex in regulating immune responses to vaccination. However, these findings have been limited to adults for both human and animal models. As a result, our understanding of the impact of sex on vaccine responses in the newborn is highly limited. Here, we probe this important question using a newborn non-human primate model. We leveraged our prior analysis of two cohorts of newborns, with one being mother-reared and one nursery-reared. This provided adequate numbers of males and females to interrogate the impact of sex on the response to inactivated influenza vaccines alone or adjuvanted with R848, flagellin, or both. We found that, in contrast to what has been reported in adults, the non-adjuvanted inactivated influenza virus vaccine induced similar levels of virus-specific IgG in male and female newborns. However, the inclusion of R848, either alone or in combination with flagellin, resulted in higher antibody titers in females compared to males. Sex-specific increases in the neutralizing antibody were only observed when both R848 and flagellin were present. These data, generated in the highly translational NHP newborn model, provide novel insights into the role of sex in the immune response of newborns.

Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab

Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay. To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment. This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023. Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year). Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed. Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment. The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.

Distinct Adverse Reactions to mRNA, Inactivated Virus, and Adenovirus Vector COVID-19 Vaccines: Insights from a Cohort Study on Atopic and Non-Atopic Subjects in Brazil.

The emergence of COVID-19 caused by SARS-CoV-2 prompted an unprecedented global response to develop vaccines at an accelerated pace. Messenger RNA (mRNA) and adenovirus vector vaccines emerged as the frontrunners in global immunization efforts, significantly reducing hospitalization, severity, and mortality, supplemented by inactivated virus-based vaccines in developing countries. However, concerns regarding adverse effects, including allergic reactions, have been raised. This study aimed to investigate the adverse effects following COVID-19 vaccination, particularly in atopic and non-atopic individuals. A cohort of 305 volunteers receiving BNT162, ChAdOx1, or CoronaVac vaccines were assessed based on a Skin Prick Test (SPT), specific IgE levels, and clinical history of asthma and rhinitis. Adverse effects were self-reported and scored across the different vaccination shots. The results indicated a notable presence of mild adverse effects following the first and third doses, regardless of vaccine type. ChAdOx1 recipients experienced more adverse effects compared to those receiving BNT162 and CoronaVac, including headaches, muscle pain, fever, chills, nausea, and flu-like symptoms. Atopic individuals receiving ChAdOx1 reported more adverse effects, such as muscle pain, fever, and chills, compared to non-atopic individuals. Conversely, headaches were more frequently reported in non-atopic individuals receiving BNT162 compared to atopic individuals. No anaphylaxis or allergic reactions were reported, indicating valuable evidence supporting the safety of COVID-19 vaccination in individuals with respiratory allergies. This study highlights the importance of understanding vaccine-related adverse effects, particularly in vulnerable populations, to inform vaccination strategies and address safety concerns in global immunization campaigns.

Immunogenicity and safety of concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine in Chinese adults: An open-label, randomized, controlled trial

ABSTRACT The immunogenicity and safety of the concomitant administration of recombinant COVID-19 vaccine and quadrivalent inactivated influenza vaccine (Split Virion) (QIIV) in Chinese adults are unclear. In this open-label, randomized controlled trial, participants aged ≥ 18 years were recruited. Eligible healthy adults were randomly assigned (1:1) to receive QIIV at the same time as the first dose of COVID-19 vaccine (simultaneous-group) or 14 days after the second dose of COVID-19 vaccine (non-simultaneous-group). The primary outcome was to compare the difference in immunogenicity of QIIV (H1N1, H3N2, Yamagata, and Victoria) between the two groups. A total of 299 participants were enrolled, 149 in the simultaneous-group and 150 in the non-simultaneous-group. There were no significant differences in geometric mean titer (GMT) [H1N1: 386.4 (95%CI: 299.2–499.0) vs. 497.4 (95%CI: 377.5–655.3); H3N2: 66.9 (95%CI: 56.1–79.8) vs. 81.4 (95%CI: 67.9–97.5); Yamagata: 95.6 (95%CI: 79.0–115.8) vs. 74.3 (95%CI: 58.6–94.0); and Victoria: 48.5 (95%CI: 37.6–62.6) vs. 65.8 (95%CI: 49.0–88.4)] and seroconversion rate (H1N1: 87.5% vs. 90.1%; H3N2: 58.1% vs. 62.0%; Yamagata: 75.0% vs. 64.5%; and Victoria: 55.1% vs. 62.8%) of QIIV antibodies between the simultaneous and non-simultaneous groups. For the seroprotection rate of QIIV antibodies, a higher seroprotection rate of Yamagata antibody was observed only in the simultaneous-group than in the non-simultaneous-group [86.0% vs. 76.0%, p = .040]. In addition, no significant difference in adverse events was observed between the two groups (14.2% vs. 23.5%, p = .053). In conclusion, no immune interference or safety concerns were found for concomitant administration of COVID-19 vaccine with QIIV in adults aged ≥ 18 years.

Minimal Determinants for Lifelong Antiviral Antibody Responses in Mice from a Single Exposure to Virus-like Immunogens at Low Doses.

The durability of an antibody (Ab) response is highly important for antiviral vaccines. However, due to the complex compositions of natural virions, the molecular determinants of Ab durability from viral infection or inactivated viral vaccines have been incompletely understood. Here we used a reductionist system of liposome-based virus-like structures to examine the durability of Abs from primary immune responses in mice. This system allowed us to independently vary fundamental viral attributes and to do so without additional adjuvants to model natural viruses. We show that a single injection of protein antigens (Ags) orderly displayed on a virion-sized liposome is sufficient to induce a long-lived neutralizing Ab (nAb) response. The introduction of internal nucleic acids dramatically modulates the magnitude of Ab responses without an alteration of the long-term kinetic trends. These Abs are characterized by very slow off-rates of ~0.0005 s-1, which emerged as early as day 5 after injection and these off-rates are comparable to that of affinity-matured monoclonal Abs. A single injection of these structures at doses as low as 100 ng led to lifelong nAb production in mice. Thus, a minimal virus-like immunogen can give rise to potent and long-lasting antiviral Abs in a primary response in mice without live infection. This has important implications for understanding both live viral infection and for optimizing vaccine design.

How has research on the effectiveness and safety of COVID-19 vaccination been evaluated: a scope review with emphasis on CoronaVac.

The control of the COVID-19 epidemic has been focused on the development of vaccines against SARS-CoV-2. All developed vaccines have reported safety and efficacy results in preventing infection and its consequences, although the quality of evidence varies depending on the vaccine considered. Different methodological designs have been used for their evaluation, which can influence our understanding of the effects of these interventions. CoronaVac is an inactivated vaccine, and it has been assessed in various studies, including clinical trials and observational studies. Given these differences, our objective was to explore the published information to answer the question: how has the efficacy/effectiveness and safety of CoronaVac been evaluated in different studies? This is to identify potential gaps and challenges to be addressed in understanding its effect. A scoping review was carried out following the methodology proposed by the Joanna Briggs Institute, which included studies carried out in humans as of 2020, corresponding to systematic reviews, clinical trials, analytical or descriptive observational studies, in which the effectiveness and/or safety of vaccines for COVID19 were evaluated or described. There were no age restrictions for the study participants. The efficacy/effectiveness and safety of this vaccine was assessed through 113 studies. Nineteen corresponded to experimental studies, 7 of Phase II, 5 of Phase IV, and 4 were clinical trials with random assignment. Although some clinical trials with random assignment have been carried out, these have limitations in terms of feasibility, follow-up times, and with this, the possibility of evaluating safety outcomes that occur with low frequencies. Not all studies have used homogeneous methods of analysis. Both the prevention of infection, and the prevention of outcomes such as hospitalization or death, have been valued through similar outcomes, but some through multivariate analysis of dependencies, and others through analysis that try to infer causally through different control methods of confounding. Published information on the evaluation of the efficacy/effectiveness and safety of the CoronaVac is abundant. However, there are differences in terms of vaccine application schedules, population definition, outcomes evaluated, follow-up times, and safety assessment, as well as non-standardization in the reporting of results, which may hinder the generalizability of the findings. It is important to generate meetings and consensus strategies for the methods and reporting of this type of studies, which will allow to reduce the heterogeneity in their presentation and a better understanding of the effect of these vaccines.

Effect of physical exercise on inactivated COVID-19 vaccine antibody response in the elderly.

Physical exercise has been proposed as a new alternative to chemical adjuvants. To investigate the relationship between regular exercise and post-vaccination antibody response in the elderly. The study was conducted with the elderly over the age of 65. 30participants we randomized into 2groups and divided into exercise and control groups. The experimental group received a 12-week exercise program. The control group was followed up without any exercise. The day on which the second dose of the vaccine was administered to all participants was considered day 0. The antibody level in the serum samples was taken 15days and 12weeks after the vaccination. The antibody concentration was measured after the second dose of vaccination. The mean antibody level in the control group was 69.4U/ml and 56.4U/ml 15days and 12weeks after the second vaccination. The mean antibody level in the exercise group was 74U/ml and 71.6U/ml 15days and 12weeks after the second vaccination. Regular exercise of light to moderate intensity may increase post-vaccination antibody response in the elderly. Therefore, exercise can be used as a behavioral adjuvant to improve the vaccine efficacy in the elderly.

Evaluation of Immune Protection of a Bivalent Inactivated Vaccine against Aeromonas salmonicida and Vibrio vulnificus in Turbot

The Aeromonas salmonicida is responsible for causing furunculosis in various fish species. Furunculosis is a ubiquitous disease that affects the aquaculture industry and causes the mass mortality of turbot. Vibrio vulnificus is a pathogen that causes skin ulcers and hemorrhagic septicemia in fish, resulting in significant mortality in aquaculture. In this study, we have established a bivalent inactivated vaccine against A. salmonicida and V. vulnificus with Montanide™ ISA 763 AVG as an adjuvant. This bivalent inactivated vaccine was used to immunize turbot by intraperitoneal injection, and the relevant immune indexes were detected. The results demonstrate that the bivalent inactivated vaccine exhibited a relative percent survival (RPS) of 77% following A. salmonicida and V. vulnificus intraperitoneal challenge. The vaccinated group exhibited higher levels of acid phosphatase activity and lysozyme activity compared to the control group. ELISA results showed a significant increase in serum antibody levels in immunized turbot, which was positively correlated with immunity. In the kidney tissue, related immune genes (TLR5, CD4, MHCI and MHCII) were up-regulated significantly, showing that the vaccine can induce cellular and humoral immune responses in turbot. In conclusion, the bivalent inactivated vaccine against A. salmonicida and V. vulnificus was immunogenic, efficiently preventing turbot from infection, which has the potential to be applied in aquaculture.

Correlation between 146S Antigen Content in Foot-and-Mouth Disease Inactivated Vaccines and Immunogenicity Level and Vaccine Potency Alternative Test Methods.

To investigate the association between 146S antigen contents in FMD inactivated vaccines and levels of antiviral immunity, this study vaccinated 30 kg pigs with three batches of FMD types O and A bivalent inactivated vaccines. Antibody titers and interferon-gamma (IFN-γ) secretion levels were measured on days 7, 14, 21, and 28 after primary immunization and on days 14 and 28 following booster immunization to assess associations between 146S contents and both antibody titers and IFN-γ secretion levels. Furthermore, 30 kg pigs were vaccinated with 46 batches of FMD type O inactivated vaccines and challenged on day 28, after which PD50 values were determined to evaluate the association between 146S content and PD50. The findings suggested that antibody titers and IFN-γ secretion levels at specific time points after immunization were positively associated with 146S contents. Additionally, 146S content showed a positive correlation with PD50, with greater PD50 values recorded for 146S contents ranging from 4.72 to 16.55 µg/dose. This investigation established a significant association between the 146S content in FMD inactivated vaccines and induced immune response against FMDV, thereby emphasizing its critical role in vaccine quality control. The determination of 146S content could serve as a new method for potency testing, offering an alternative to animal challenge tests.

Quantitation of Enterovirus A71 Empty and Full Particles by Sedimentation Velocity Analytical Ultracentrifugation.

The enterovirus A71 (EV71) inactivated vaccine is an effective intervention to control the spread of the virus and prevent EV71-associated hand, foot, and mouth disease (HFMD). It is widely administered to infants and children in China. The empty particles (EPs) and full particles (FPs) generated during production have different antigenic and immunogenic properties. However, the antigen detection methods currently used were established without considering the differences in antigenicity between EPs and FPs. There is also a lack of other effective analytical methods for detecting the different particle forms, which hinders the consistency between batches of products. In this study, we analyzed the application of sedimentation velocity analytical ultracentrifugation (SV-AUC) in characterizing the EPs and FPs of EV71. Our results showed that the proportions of the two forms could be quantified simultaneously by SV-AUC. We also determined the repeatability and accuracy of this method and found that both parameters were satisfactory. We assessed SV-AUC for bulk vaccine quality control, and our findings indicated that SV-AUC can be used effectively to analyze the percentage of EPs and FPs and monitor the consistency of the process to ensure the quality of the vaccine.

Spike 1 trimer, a nanoparticle vaccine against porcine epidemic diarrhea virus induces protective immunity challenge in piglets.

Porcine epidemic diarrhea virus (PEDV) is considered the cause for porcine epidemic diarrhea (PED) outbreaks and hefty losses in pig farming. However, no effective commercial vaccines against PEDV mutant strains are available nowadays. Here, we constructed three native-like trimeric candidate nanovaccines, i.e., spike 1 trimer (S1-Trimer), collagenase equivalent domain trimer (COE-Trimer), and receptor-binding domain trimer (RBD-Trimer) for PEDV based on Trimer-Tag technology. And evaluated its physical properties and immune efficacy. The result showed that the candidate nanovaccines were safe for mice and pregnant sows, and no animal death or miscarriage occurred in our study. S1-Trimer showed stable physical properties, high cell uptake rate and receptor affinity. In the mouse, sow and piglet models, immunization of S1-Trimer induced high-level of humoral immunity containing PEDV-specific IgG and IgA. S1-Trimer-driven mucosal IgA responses and systemic IgG responses exhibited high titers of virus neutralizing antibodies (NAbs) in vitro. S1-Trimer induced Th1-biased cellular immune responses in mice. Moreover, the piglets from the S1-Trimer and inactivated vaccine groups displayed significantly fewer microscopic lesions in the intestinal tissue, with only one and two piglets showing mild diarrhea. The viral load in feces and intestines from the S1-Trimer and inactivated vaccine groups were significantly lower than those of the PBS group. For the first time, our data demonstrated the protective efficacy of Trimer-Tag-based nanovaccines used for PEDV. The S1-Trimer developed in this study was a competitive vaccine candidate, and Trimer-Tag may be an important platform for the rapid production of safe and effective subunit vaccines in the future.

Clinical trial of tolerability, safety and immunogenicity of influenza inactivated split-vaccine Flu-M in children aged 6 to 17 years

Purpose. To evaluate the tolerability, safety and immunogenicity of influenza inactivated split flu vaccine Flu-M during single immunization of children aged 6 to 17 years.Materials and methods. A multicentre double-blind comparative randomised clinical trial of influenza inactivated split vaccine Flu-M for immunisation of children aged 6 to 17 years (the reference agent – Ultrix vaccine) was conducted. Children aged 12 to 17 years inclusive (300 children) were studied at stage I, and children aged 6 to 12 years (300 children) at stage II. Volunteers of each age category were randomised 1:1 into 2 groups comparable in sex and age, one was vaccinated with Flu-M vaccine and the other with Ultrix vaccine. The follow-up, including various laboratory and clinical tests, lasted for 28 days from the time of vaccination.Results. Both vaccines were well tolerated by children aged 12 to 17 years and by children aged 6 to 12 years. There were no severe or serious adverse events. By all criteria of immunogenicity evaluation, vaccine Flu-M was not inferior to the comparison vaccine Ultrix.Conclusion. Influenza inactivated split Flu-M vaccine produced by SPbNIIVS is approved for use for specific prophylaxis of influenza in children aged 6 to 17 years in the Russian Federation, the Republic of Belarus, Latin America and the Caribbean.The trial is registered at ClinicalTrials. gov (NCT 05317767).

A Historical Perspective on Respiratory Syncytial Virus Prevention: A Journey Spanning Over Half a Century From the Setback of an Inactive Vaccine Candidate to the Success of Passive Immunization Strategy.

The efforts to prevent respiratory syncytial virus (RSV) infection in infants span over half a century. RSV vaccine development began in the 1960s, and it confronted a significant disappointment after testing a formalin-inactivated RSV (FI RSV) vaccine candidate. This inactivated RSV vaccine was not protective. A large number of the vaccinated RSV-naive children, when subsequently exposed to natural RSV infection from wild-type virus in the community, developed severe lung inflammation termed enhanced respiratory disease. This resulted in a halt in RSV vaccine development. In the 1990s, attention turned to the potential for passive protection against severe RSV disease with immunoglobulin administration. This led to studies on using standard intravenous immunoglobulins in high-risk infants, followed by high-titer RSV immunoglobulin preparation and, subsequently, the development of RSV monoclonal antibodies. Over the past 25 years, palivizumab has been recognized as a safe and effective monoclonal antibody as a prevention strategy for RSV in high-risk children. Its high cost and need for monthly administration, however, has hindered its use to ~2% of the birth cohort, neglecting the vast majority of newborns, including healthy full-term infants who comprise the largest portion of RSV hospitalizations and the greatest part of the burden of RSV disease. Still these efforts, helped pave the way for the present advances in RSV prevention that hold promise for mitigating severe RSV disease for all infants.

Mucosal immunization with a low-energy electron inactivated respiratory syncytial virus vaccine protects mice without Th2 immune bias.

The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.) vaccines against RSV have been approved for elderly and pregnant women. Noninvasive mucosal vaccination, e.g., by inhalation, offers an alternative against respiratory pathogens like RSV. Effective mucosal vaccines induce local immune responses, potentially resulting in the efficient and fast elimination of respiratory viruses after natural infection. To investigate this immune response to an RSV challenge, low-energy electron inactivated RSV (LEEI-RSV) was formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) or 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DD-LEEI-RSV) for vaccination of mice intranasally. As controls, LEEI-RSV and formalin-inactivated-RSV (FI-RSV) were used via i.m. vaccination. The RSV-specific immunogenicity of the different vaccines and their protective efficacy were analyzed. RSV-specific IgA antibodies and a statistically significant reduction in viral load upon challenge were detected in mucosal DD-LEEI-RSV-vaccinated animals. Alhydrogel-adjuvanted LEEI-RSV i.m. showed a Th2-bias with enhanced IgE, eosinophils, and lung histopathology comparable to FI-RSV. These effects were absent when applying the mucosal vaccines highlighting the potential of DD-LEEI-RSV as an RSV vaccine candidate and the improved performance of this mucosal vaccine candidate.

Effects of astragalus extract, levamisole and ascorbic acid on humoral immunity in chickens vaccinated with newcastle disease vaccines

This study was designed to assess the effects of Astragalus extract, levamisole and ascorbic acid on the humoral immune response of chickens vaccinated with live and inactivated Newcastle Disease (ND) vaccines. Sixty day-old Cobb500 broiler chicks were used for the study. At day old, the maternally derived antibodies (MDA) to ND virus was determined and the chicks were then housed in a bio-secured pen with water and feed given ad-lib. On the sixth day, the MDA decay was determined thereafter, the chicks were shared into 4 treatment groups. Group A (Astragalus extract); Group B (levamisole); Group C (ascorbic acid) and Group D (Control) of 15 chicks each. Response to ND vaccinations was determined through bleeding to obtain sera for haemagglutination inhibition test at 7 and 14 days except for the second booster with inactivated Komarov vaccine where it was done at 7, 14 and 21 days post vaccination respectively. Antibody titres in the chicks 7 days post first dose of vaccination with La Sota was high in all the treatment groups above the control with 100 % of the chicks having protective antibody titre of ≥4 log2 until day 30 when the antibody titres in all the groups dropped drastically following the second dose of live La Sota vaccination as the first booster vaccine. However, following the second booster with inactivated Komarov the antibody titres increased in all the treatment groups in comparison to the control especially in groups B and C with GMTs of 5.8 ± 0.19 log2 and 6.1 ± 0.27 log2 respectively. We observed that ascorbic acid and Levamisole may have humoral immuno-stimulating effects on vaccinated chickens through yet to be fully explored mechanism. It is recommended that ascorbic acid or levamisole could be used during vaccinations as immuno-stimulating agents to enhance humoral antibody response in vaccinated flocks.

Immunological properties of inactivated vaccines against Newcastle disease based on virus antigens VII and II the genotype

Newcastle disease (ND) is now widely spread in many countries of Eurasia, Africa and the Americas and causes significant economic damage to poultry farming. New NDinfected localities are reported in the Russian Federation every year; besides, the number of farms with vaccinated poultry demonstrating high specific antibody titres, decreased performance and survivability while being asymptomatic has increased. This is attributed to the virus evolution leading to the emergence of new genotypes represented by highly virulent strains. Since 2019, subgenotype VII-L has been isolated from Newcastle disease outbreaks in Russia. The vaccines currently available on the market do not confer appropriate protection against it due to the lack of antigenic matching between vaccine strains and this subgenotype. The development of a vaccine based on subgenotype VII -L will allow to ensure protection of poultry flocks against Newcastle disease caused by new NDV isolates. The immunological properties of emulsion inactivated vaccine against Newcastle disease based on genotype VII NDV (ARRIAH G7 strain) antigen were studied in 30-day-old Hisex Brown chickens. A similar vaccine based on genotype II NDV LaSota strain antigen was used as control. Tests of different immunizing antigen doses were carried out. The vaccines were tested for induced humoral immunity level (HI antibody titres), as well as for protective effect (protective index) after challenge with a highly virulent genotype VII NDV strain. The tests revealed that the antigenic activity and protective effect of both vaccines depended on the antigen concentration in the inoculation volume. Antibody titres were always higher when homologous antigens were used in HI tests. The vaccine based on the antigen of ARRIAH G7 strain (homologous to the challenge strain) was more effective than the control vaccine. Less ARRIAH G7 strain antigen was required to protect 50% of vaccinated poultry, compared with LaSota strain antigen. The comparative assessment of the same doses of the antigens showed that the vaccine based on ARRIAH G7 strain antigen had better immunological properties. The tested antigens demonstrated 18.3% bilateral affinity.

Evaluation of antibody responses in healthy individuals receiving SARS-CoV-2 inactivated vaccines

Inactivated coronavirus disease 2019 (COVID-19) vaccines such as CoronaVac and BBIBP-CorV have been widely used in China. However, more investigation is still needed to understand antibodies' duration and effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the real world. In this study, 575 participants who had been vaccinated with two or three doses of the inactivated vaccine were recruited. Serum samples were collected and tested for anti-spike IgG and neutralizing antibodies against SARS-CoV-2 (original strain, Dela, and Omicron). Unsurprisingly, a third dose of the vaccine significantly enhanced antibody responses against SARS-CoV-2 and its variants. However, despite a booster dose, the neutralizing antibody levels against Omicron, particularly the BA.5.2 subvariant, remained low. There was no sex bias, but an age bias was observed. Notably, the predominant IgG subclass antibodies were IgG1 and IgG2, with a much lower level of IgG4. After the booster shot, the ratio of IgG4 to IgG1 significantly increased. The observation of IgG1 to the IgG4 class switch after repeated inactivated vaccinations underscores the importance of continuous monitoring of subclass antibody responses. Further clinical investigations are required to understand the implications of this class switch for optimizing immunization strategies.

Unveiling the micronutrient-immunity puzzle in inactivated COVID-19 vaccination: A comprehensive analysis of circulating micronutrient levels and humoral responses in healthy adults.

While micronutrients are crucial for immune function, their impact on humoral responses to inactivated COVID-19 vaccination remains unclear. We investigated the associations between seven key micronutrients and antibody responses in 44 healthy adults with two doses of an inactivated COVID-19 vaccine. Blood samples were collected pre-vaccination and 28 days post-booster. We measured circulating minerals (iron, zinc, copper, and selenium) and vitamins (A, D, and E) concentrations alongside antibody responses and assessed their associations using linear regression analyses. Our analysis revealed inverse associations between blood iron and zinc concentrations and anti-SARS-CoV-2 IgM antibody binding affinity (AUC for iron: β = -258.21, p < 0.0001; zinc: β = -17.25, p = 0.0004). Notably, antibody quality presented complex relationships. Blood selenium was positively associated (β = 18.61, p = 0.0030), while copper/selenium ratio was inversely associated (β = -1.36, p = 0.0055) with the neutralizing ability against SARS-CoV-2 virus at a 1:10 plasma dilution. There was no significant association between circulating micronutrient concentrations and anti-SARS-CoV-2 IgG binding affinity. These findings suggest that circulating iron, zinc, and selenium concentrations and copper/selenium ratio, may serve as potential biomarkers for both quantity (binding affinity) and quality (neutralization) of humoral responses after inactivated COVID-19 vaccination. Furthermore, they hint at the potential of pre-vaccination dietary interventions, such as selenium supplementation, to improve vaccine efficacy. However, larger, diverse studies are needed to validate these findings. This research advances the understanding of the impact of micronutrients on vaccine response, offering the potential for personalized vaccination strategies.