Vaccine Vector Research Articles

A simplified vaccination program elicits an immune response comparable to a complex standard vaccination program in commercial layers under field conditions.

Newcastle disease (ND) is a notifiable avian disease responsible for several panzootics, which has resulted in the establishment of mandatory vaccination programs against the virus in several countries including Denmark. This study compared the immune response elicited in layers by the standard vaccination program for ND of a Danish commercial egg production facility with a simplified version of the vaccination program. A commercial flock of layers was followed for 77 weeks from hatching to culling. The flock was divided into two groups according to vaccination program and housed separately. One group received the standard vaccination program consisting of a vector vaccine, a live vaccine (administered twice) and an inactivated vaccine (standard vaccination program). The other group received a newly marketed vector vaccine and the inactivated vaccine of the standard vaccination program (simplified vaccination program). Blood samples were collected at regular intervals from 30 randomly selected layers in each group until culling (77 weeks of age) and analysed for ND antibodies by ELISA assays, which measured antibodies against the nucleoprotein or fusion protein, and hemagglutination inhibition tests. Both vaccination programs provided lasting antibodies until 77 weeks. The simplified vaccination program showed significantly higher fusion protein antibodies and a markedly earlier onset of immunity at five weeks of age (97-100 % seroprevalence) than the standard program. The standard vaccination program reached the same seroprevalence at 14 and 24 weeks of age based on fusion protein antibodies and HI titres, respectively. The inactivated vaccine elicited a boost in antibody titres in both groups, however, boosting with the live vaccine used in the standard vaccination program did not result in an increased antibody response. This might indicate that administering of a vector vaccine prior to a live vaccine inhibits the serological response to the live vaccine.

HeterologousPrime-Boost immunizationwithAdenoviral vector and recombinant subunit vaccines strategies against dengue virus type2.

Dengue virus (DENV) remains a significant public health threat in tropical and subtropical regions, with effective antiviral treatments and vaccines still not fully established despite extensive research. A critical aspect of vaccine development for DENV involves selecting proteins from both structural and non-structural regions of the virus to activate humoral and cellular immune responses effectively. In this study, we developed a novel vaccine for dengue virus serotype 2 (DENV2) using a heterologous Prime-Boost strategy that combines an adenoviral vector (Ad) with subunit vaccines. The vaccine design included non-structural protein 1 (NS1), envelope protein domain III (EDIII), and the bc-loop of envelope domain II (EDII) as conserved epitopes. These antigens were fused into a single construct P1 and inserted into the pAdTrack-CMV vector to produce a recombinant adenovirus (rAd5-P1) via homologous recombination in E. coli. The examination of the immune response indicated that strong humoral and cellular immunity was generated in various groups of mice. Additionally, the group receiving a heterologous regimen of recombinant adenovirus and protein showed a superior balance of humoral and cellular immunity in terms of IgG2a/IgG1 and INF-γ /IL-4 ratios. These findings validate the vaccine design's ability to utilize both structural and non-structural proteins to generate strong immune responses on two platforms. The promising results from the heterologous regimen highlight its potential as an effective DENV2 vaccine candidate. This research offers significant insights into developing safe and effective DEN vaccines, contributing to efforts to control DENV infections.

An effective antiviral strategy based on silence of susceptibility genes through cucumber mosaic virus (CMV) attenuated vaccine vector.

Plant viruses represent a major threat to agriculture, affecting a wide range of crops with substantial economic losses. This study presented a novel strategy for managing plant viral diseases through the development an attenuated vaccine utilizing cucumber mosaic virus (CMV) for virus-induced gene silencing (VIGS) targeting susceptibility gene. TOBAMOVIRUS MULTIPLICATION 2A (TOM2A) gene was identified as a critical factor that enhances susceptibility to TMV infection in plants. Two vaccines were constructed based on CMV attenuated vaccine vector-CR2V. The first vaccine was constructed by incorporating NtTOM2A fragments into CR2V, while the second vaccine was developed by inserting both NtTOM2A fragments and TMV-p183 fragments into CR2V. Each vaccine constructs significantly reduced TMV accumulation, exhibited no adverse effects on plant growth, and maintained stability of the inserted sequences up to 21 days post-vaccination (dpv) in vivo. The study underscored the potential of utilizing engineered plant viruses as environmentally sustainable vaccines for mitigating viral diseases in agriculture.

Spray vaccination with a safe and bivalent H9N2 recombinant chimeric NDV vector vaccine elicits complete protection against NDV and H9N2 AIV challenge

Newcastle disease virus (NDV) and H9N2 avian influenza virus (AIV) represent significant pathogenic risks to the poultry industry, leading to considerable economic losses. Vaccination is a widely used preventive measure against these pathogens, yet the lack of a live bivalent vaccine targeting NDV and H9N2 AIV imposes a heavy vaccination burden. Previously, we constructed a genotype-matched chimeric NDV vector, LX-OAI4S, in which the genotype I NDV backbone was replaced with the ectodomain of haemagglutinin-neuraminidase (HN) and modified using the attenuated F gene from the genotype VII vaccine strain A-VII. Based on the LX-OAI4S vector, we successfully generated three H9N2 recombinant viruses: LX-OAI4S-NPU-HA, LX-OAI4S-MU-HA, and LX-OAI4S-HNU-HA. These recombinants incorporated the H9N2 HA gene, flanked by untranslated regions (UTRs) from the NP, M, or HN gene of the NDV LX strain, inserted between the P and M genes of LX-OAI4S. The vaccine candidate LX-OAI4S-NPU-HA induced a more robust immune response in chickens against H9N2 AIV and NDV than the other two recombinants. This response effectively protects against virus shedding and lethal virus challenge. Furthermore, spray vaccination with LX-OAI4S-NPU-HA showed protective efficacy against H9N2 AIV and NDV. This study offers a promising strategy for comprehensive protection in regions threatened by H9N2 AIV and NDV.

Effective Immune Protection of Mice from Murine Cytomegalovirus Infection by Oral Salmonella-Based Vaccine Expressing Viral M78 Antigen

Background: Human cytomegalovirus (CMV) is the most common cause of viral congenital infections worldwide. The development of effective vaccines against human CMV infection and disease is a high priority. Attenuated Salmonella are attractive oral vaccine vectors against human diseases because they can be administrated orally. Methods: In this study, an attenuated Salmonella strain was generated as an oral vaccine vector for the delivery and expression of the M78 protein of murine cytomegalovirus (MCMV). Using the MCMV infection of mice as the CMV infection model, we characterized the immune responses and protection induced by the constructed Salmonella-based vaccine. Results: The generated Salmonella-based vaccine, v-M78, which contained an M78 expression plasmid construct, carried out gene transfer efficiently for M78 expression and showed little pathogenicity and virulence in mice. In orally vaccinated mice, v-M78 induced anti-MCMV serum IgG and mucosal IgA responses and also elicited anti-MCMV T cell responses. Furthermore, mice immunized with v-M78 were protected from intraperitoneal and intranasal challenges with MCMV. The v-M78 vaccination reduced the titers of the challenged viruses in spleens, livers, lungs, and salivary glands. Conclusions: These results provide the first direct evidence that a Salmonella-based vaccine expressing M78 elicits strong humoral and cellular immune responses and induces immune protection against MCMV infection. Furthermore, our study demonstrates the potential of using Salmonella-based oral vaccines against CMV infection.

Waning neutralizing antibodies through 180 days after homologous and heterologous boosters of inactivated COVID-19 vaccine

To enhance the personal immunity to COVID-19, a third booster dose of inactivated COVID-19 vaccines program campaign was implemented in China. Our study endeavored to compare the dynamics of neutralizing antibodies generated by four distinct booster vaccines against three kinds of live SARS-CoV-2 virus (wild-type, Delta AY.23, and Omicron BA5.2). This cohort study involved 320 healthy individuals, who were randomly assigned to four groups, to receive boosters with inactivated vaccine (COVac and BIBP), the adenovirus type-5-vectored vaccine (Convidecia), and the recombinant protein-based vaccine (Zifivax), respectively, all the vaccines studied had the Wuhan variant as their parental variant. Participants were recruited from December 2021 to June 2022, with a follow-up period of 180 days. We evaluated humoral immune responses and their longevity by measuring the geometric mean titers (GMTs) of neutralizing antibodies against the SARS-CoV-2 virus at various time points post-boost. After 180 days of follow-up, 310 participants completed the study. Across all booster groups, neutralizing antibodies against the wild-type virus declined sharply within the first 90 days, accounting for an 81.24 to 92.34% reduction, then slowed down with gradually decreasing decay rates. By day 14 of post-boost, the ability to neutralize the Delta variant slightly diminished compared to the wild-type, whereas neutralizing antibodies against the Omicron variant exhibited a more pronounced decline, ranging from 10.78 to 19.88 times lower than those against the wild-type. Notably, heterologous boosting with the Convidecia vaccine maintained higher GMTs of neutralizing antibodies against both Delta and Omicron variants compared to the other boosters. At 180 days of post-boost, GMTs of neutralizing antibodies against SARS-CoV-2 had substantially decreased, yet individuals who received the Convidecia vaccine still exhibited higher titers than those who received other boosters. In summary, neutralizing antibody levels significantly waned 180 days after the third vaccine dose, with the most pronounced decline occurring within the initial 90 days. Heterologous boosting with Convidecia demonstrated a more robust, durable, and broad humoral immune response compared to boosting with inactivated vaccines or Zifivax, suggesting that adenovirus vector vaccines possess a special advantage in the realm of vaccine development for preventing infectious diseases.

The Current Status in Terms of Vaccination for Individuals Infected with Human Immunodeficiency Virus

Human immunodeficiency virus (HIV)-infected individuals have an increased risk of various infections due to their impaired host immune system, resulting in higher morbidity and mortality rates. These patients severely suffered during the COVID-19 epidemic, the influenza epidemic and the spread of monkeypox. Reducing serious infections is one of the most important measures to improve HIV-infected individuals’ quality and length of life. Based on the preparation processes and their antigenic properties, vaccines are divided into several types, including inactivated vaccines, attenuated live vaccines, recombinant protein vaccines, toxoid vaccines, polysaccharide vaccines, polysaccharide (protein) combined vaccines, nucleic acid vaccines, viral vector vaccines, etc. With the innovation of vaccine preparation technology in recent years and the acceleration of vaccine approval and market launch, more and more vaccine products suitable for HIV-infected individuals have become available. Because of their deficient immune systems, the type of vaccines and the schedule of vaccinations available to individuals living with HIV are sometimes different from those with healthy immune systems. This article reviewed the current status of vaccination in and shed light on the vaccination strategies for HIV-infected persons in terms of their safety and effectiveness.

Comparison of Phenotypes of Headaches After COVID-19 Vaccinations Differentiated According to the Vaccine Used

Background/Objectives: In this ongoing, multicenter, global cohort observational study, phenotypes of headaches after COVID-19 vaccination were directly compared between different vaccines. Methods: Phenotypes of postvaccinal headache were recorded in 18,544 participants. The study was launched immediately after the start of the global COVID-19 vaccination campaign on 12 January 2021 and continued until 1 August 2023. Specific aspects of headaches and related variables were collected via an online questionnaire. The clinical headache characteristics of patients vaccinated with the Comirnaty (BioNTech), Jcovden (Johnson & Johnson), Sputnik V (Gamelaya), Covilo (Sinopharm), Spikevax (Moderna), Vaxzevria (AstraZeneca), and Convidecia (CanSino Biologics) vaccines were investigated. Results: Across all vaccines, the median and mean latency of headache onset after vaccine administration were 12 h and 23.3 h, respectively. The median and mean headache duration were 12 h and 23.3 h, respectively. When the nonreplicating viral vector vaccine Sputnik V was used, headaches occurred the fastest, with a latency of 17 h. The latencies for the Vaxzevria and Convidecia nonreplicating viral vector vaccines were 14.9 h and 19.1 h, respectively. The Covilo inactivated whole-virus vaccine had a latency of 20.5 h. The latencies of the mRNA-based Comirnaty and Spikevax vaccines were 26.0 h and 22.02 h, respectively. Analysis of variance revealed no significant differences in the mean duration of postvaccinal headache for the vaccines tested. Compared with the Comirnaty, Covilo, and Vaxzevria vaccines, the Spikevax vaccine induced significantly greater headache intensities. Vaxzevria was associated with a significantly higher frequency of concomitant symptoms than the other vaccines. Conclusions: The phenotype of postvaccinal headache can vary significantly between vaccines. These results have clinical implications for differentiating between postvaccinal headache and other primary and secondary headaches. This knowledge is clinically relevant in differentiating life-threatening vaccination complications, such as thrombotic syndromes, which are also associated with headaches. Based on these results, new diagnostic criteria for postvaccinal headaches can be developed.

Progress in African Swine Fever Vector Vaccine Development

African swine fever (ASF) is a highly lethal, infectious, hemorrhagic fever disease, characterized by an acute mortality rate approaching 100%. It is highly contagious, and results in significant losses to the global hog industry as it spreads. Despite incremental progress in research on the African swine fever virus (ASFV), a safe and effective commercial vaccine has yet to be developed. Vector vaccines, a promising type of vaccine, offer unique advantages, and are a primary focus in ASFV vaccine research. This paper focuses on the characteristics of viral, bacterial, and yeast vector vaccines; elucidates the immunological mechanisms associated with antigens; lists the types of antigens that have significant potential; discusses the feasibility of using exogenously expressed cytokines to enhance the protective power of vector vaccines; and, finally, discusses the types of vectors that are commonly used and the latest advances in this field.

P0701 Trans-continental analysis of determinants of response to COVID-19 vaccination in 2268 patients with Inflammatory Bowel Disease

Abstract Background Little is known about the relative efficacy of available COVID-19 vaccine types around the world in immune-compromised patients with inflammatory bowel disease (IBD).1,2 We aimed to compare antibody responses to SARS-CoV-2 in patients with IBD who had received mRNA, vector, and inactivated virus vaccines and the impact of medications thereof among multinational sites. Methods Serum samples taken after 1st, 2nd, and 3rd doses of COVID-19 vaccines from patients with IBD seen at 13 sites across Europe, Asia, and North America were prospectively collected between January 2021 and November 2022. We measured anti-Spike (S) and anti-nucleocapsid (N) antibody levels. To identify determinants of serological responses to vaccination, both univariate and multivariate analyses were conducted. Results There were a total of 2,268 patients, including 1,279 Crohn’s disease (CD) and 868 ulcerative colitis (UC) (Table 1). 1552 patients had an mRNA vaccine, 590 an adenovirus vaccine, and 98 an inactivated virus vaccine. At 14-84 days, 85-168 days, and 169+ days after completing a full vaccination series, the proportion of patients who were positive for anti-S antibodies were 98% (n=922/939), 96% (n=700/731), and 98% (n=677/692) for mRNA, 95% (n=378/396), 89% (n=55/62), and 97% (n=33/34) for adenovirus, and 72% (n=21/29), 84% (n=31/37), and 95% (n=55/58) for inactivated virus vaccine, respectively. On univariate analysis, rates of serological response were highest in those who received mRNA vaccines at all six time periods (Figure 1a). Adenovirus vaccine response rates closely resembled the rate of seropositivity in mRNA vaccinated patients. In contrast, inactivated vaccines had a significantly lower percent of patients reaching seropositivity until 169 days or more after the second vaccine dose (p<0.001). Anti-TNF monotherapy and immunomodulator monotherapy were associated with the ability to obtain maximum antibody titres. However, this difference is ablated after the 3rd dose (Figure 1c). Univariate analysis also implicated geographical site, male sex, and a diagnosis of ulcerative colitis as determinants of serological responses. On multi-variable analysis, vaccine type (p < 0.001 at every time point analysed) and the use of immunomodulators (p <0.001 at time points 1 and 3) were confirmed as independent determinants of vaccine responsiveness across the study populations. Conclusion Our data suggests that while there is variability between geographical centers, the response rates are high worldwide, and the key determinants of serological response to vaccines are the use of immunosuppressive agents and vaccine class.3 These data are important considerations for better pandemic preparedness in the IBD community worldwide. References (1)Wong SY, Wellens J, Helmus D, et al. Geography Influences Susceptibility to SARS-CoV-2 Serological Response in Patients With Inflammatory Bowel Disease: Multinational Analysis From the ICARUS-IBD Consortium. Inflamm Bowel Dis. 2023;29(11):1693-1705. doi:10.1093/ibd/izad097 (2)Goodyear CS, Patel A, Barnes E, et al. Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial. Lancet Rheumatol. 2024;6(6):e339-e351. doi:10.1016/S2665-9913(24)00065-1 (3)Barnes E, Goodyear CS, Willicombe M, et al. SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease. Nat Med. 2023;29(7):1760-1774. doi:10.1038/s41591-023-02414-4

Metalloparticle-Engineered Pickering Emulsion Displaying AAV-Vectored Vaccine for Enhancing Antigen Expression and Immunogenicity Against Pathogens.

Recombinant adeno-associated viruses (rAAVs) have emerged as promising vaccine vectors due to their enduring efficacy with a single dose. However, insufficient cellular immune responses and the random and non-specific distribution of AAVs post-injection may hinder the development of AAV vaccines. Here, a novel Pickering emulsion platform stabilized by biomineralized manganese nanoparticles and aluminum hydroxide, which can rapidly and efficiently load AAVs, is reported. This platform confers AAVs with favorable in vivo distribution kinetics, diversifying AAV endocytic pathways with reduced dependency on the sialic acid receptor-mediated route, and ultimately enhancing AAV infection efficiency in antigen present cells (APCs). Concurrently, the Pickering emulsion substantially boosts endogenous 2'3'-cGAMP production, further activating the cGAS-STING pathway for stronger immune responses and improving protective efficacy in bacterial infection models. The STING pathway activation also increases AAV target gene expression, potently augmenting the cross-protective potential of AAV vaccines for COVID-19. These synergistic effects ensure that effective immune responses are induced even at one-fifth of the AAV vaccination dose, while the Pickering emulsion further reduces the accumulation of AAV in the liver, thereby improving their safety. The findings highlight the potential of Pickering emulsions as valuable enhancers for viral vectors, providing insights for their broader clinical applicability.

Unraveling Cardiovascular Risks and Benefits of COVID-19 Vaccines: A Systematic Review.

The rapid development and deployment of mRNA and non-mRNA COVID-19 vaccines have played a pivotal role in mitigating the global pandemic. Despite their success in reducing severe disease outcomes, emerging concerns about cardiovascular complications have raised questions regarding their safety. This systematic review critically evaluates the evidence on the cardiovascular effects of COVID-19 vaccines, assessing both their protective and adverse impacts, while considering the challenges posed by the limited availability of randomized controlled trial (RCT) data on these rare adverse events. In adherence to PRISMA 2020 guidelines, we conducted a systematic review using the Scopus database, incorporating articles published from January 2020 to July 2024. Our search included terms related to COVID-19 vaccines and cardiovascular conditions. We selected relevant studies from case-control studies, cohort studies, and clinical trials, while excluding descriptive analyses, cross-sectional studies, and conference reports. Case reports were also included due to the limited availability of extensive RCT data on the rare cardiovascular adverse events associated with COVID-19 vaccines. Of the 6037 articles initially screened, 410 were assessed in detail and 175 studies were ultimately included. The review identified a variety of cardiovascular adverse effects associated with COVID-19 vaccines. mRNA vaccines were primarily linked to myocarditis and pericarditis, particularly in younger males, with lower cardiac risks compared to COVID-19 infection. Adenoviral vector vaccines were associated with thrombosis and thrombocytopenia. Inactivated vaccines had fewer severe cardiovascular reports but still presented risks. Takotsubo cardiomyopathy was most commonly observed following mRNA vaccination. Case reports provided valuable additional insights into these rare events, highlighting clinical presentations and potential risk factors not fully captured by larger epidemiological studies. This review reveals a nuanced cardiovascular risk profile for COVID-19 vaccines, with mRNA vaccines linked to rare myocarditis and pericarditis in young males and a higher incidence of Takotsubo cardiomyopathy in females. Adenoviral vaccines show a notable association with thrombosis. Despite these risks, the benefits of vaccination in preventing severe COVID-19 outcomes outweigh the potential complications, underscoring the importance of continued surveillance, case report documentation, and personalized risk assessment. The inclusion of case reports was critical, as they provided valuable real-world data that complemented the findings from large-scale studies and RCTs.

Current Status and Future Trends in Myocarditis Related to the COVID-19 Vaccines: A Visual and Bibliometric Analysis.

This study aims to conduct a bibliometric and visual analysis of published studies on myocarditis and coronavirus disease 2019 (COVID-19) vaccines. The widespread epidemic of COVID-19 has caused millions of deaths and profoundly affected the global medical landscape. Studies on COVID-19 vaccination and related myocarditis have also increased significantly. To analyze the current status and trends of myocarditis and COVID-19 vaccine research by bibliometric and to elucidate research hotspots and frontiers. Based on the Web of Science Core Collection SCI-Expanded database, we utilize Excel 2019 and visualization analysis tools VOSviewer, Co-Occurrence13.2 (COOC13.2), Citespace, HistCite, and Scimago Graphica for analysis. Our study encompassed a total of 389 relevant articles, and we observed a consistent upward trend in the number of publications over time, indicating the growing interest in this subject. Among the countries and regions contributing to this body of literature, the United States emerged as the leading publisher, with Harvard Medical School being the most prominent institution associated with these studies. Notably, Matthew E. Oster from the United States emerged as one of the prominent authors in this field. Hotspot research and frontier areas include myocarditis and the different types of COVID-19 vaccines (e.g., mRNA vaccines, adenovirus vector vaccines, inactivated vaccines), the development of new vaccines in reducing the incidence and sequelae of COVID-19 without an increased incidence of myocarditis, and relief of vaccine hesitancy. Research on myocarditis and the COVID-19 vaccines has grown rapidly. Our research results can help researchers grasp the current status of myocarditis related to the COVID-19 vaccine research and find new research directions in the future.

Exploitation of Unconventional CD8 T-Cell Responses Induced by Engineered Cytomegaloviruses for the Development of an HIV-1 Vaccine.

After four decades of intensive research, traditional vaccination strategies for HIV-1 remain ineffective due to HIV-1's extraordinary genetic diversity and complex immune evasion mechanisms. Cytomegaloviruses (CMV) have emerged as a novel type of vaccine vector with unique advantages due to CMV persistence and immunogenicity. Rhesus macaques vaccinated with molecular clone 68-1 of RhCMV (RhCMV68-1) engineered to express simian immunodeficiency virus (SIV) immunogens elicited an unconventional major histocompatibility complex class Ib allele E (MHC-E)-restricted CD8+ T-cell response, which consistently protected over half of the animals against a highly pathogenic SIV challenge. The RhCMV68-1.SIV-induced responses mediated a post-infection replication arrest of the challenge virus and eventually cleared it from the body. These observations in rhesus macaques opened a possibility that MHC-E-restricted CD8+ T-cells could achieve similar control of HIV-1 in humans. The potentially game-changing advantage of the human CMV (HCMV)-based vaccines is that they would induce protective CD8+ T-cells persisting at the sites of entry that would be insensitive to HIV-1 evasion. In the RhCMV68-1-protected rhesus macaques, MHC-E molecules and their peptide cargo utilise complex regulatory mechanisms and unique transport patterns, and researchers study these to guide human vaccine development. However, CMVs are highly species-adapted viruses and it is yet to be shown whether the success of RhCMV68-1 can be translated into an HCMV ortholog for humans. Despite some safety concerns regarding using HCMV as a vaccine vector in humans, there is a vision of immune programming of HCMV to induce pathogen-tailored CD8+ T-cells effective against HIV-1 and other life-threatening diseases.

Protective potential of structural proteins of the SARS-CoV-2 virus in protecting against COVID-19

Introduction. Many different vaccines for the prevention of COVID-19 have received emergency use approval in the shortest possible time. Due to the high rate of variability of the pathogen, in this study we analyzed the variability of the structural proteins of the SARS-CoV-2 virus and compared their protective potential in protecting animals from COVID-19. The aim of the study was to compare the protective potential of the SARS-CoV-2 structural proteins in protecting animals from COVID-19. Materials and methods. The SARS-CoV-2 virus was used in the study. Transgenic mice B6.Cg-Tg(K18-ACE2)2Prlmn/J (F1) were used as model animals. Recombinant adenoviral vectors rAd5-S, rAd5-N, rAd5-M were used for immunization of animals. Various genetic, virological and immunological methods, as well as methods of working with animals, were used in the study. Results. The largest number of amino acid substitutions in the structural proteins of different SARS-CoV-2 variants was detected in glycoprotein S, the smallest — in nucleoprotein N. In the COVID-19 animal model, it was shown that only the use of glycoprotein S as a vaccine antigen allows to form protective immunity that protects 100% of animals from a lethal infection caused by the SARS-CoV-2 virus, while the use of protein N protects 50% of animals from a lethal infection, and protein M does not have a protective potential. Conclusion. The data obtained, as well as the analysis of the epidemiological efficacy of various mRNA and vector vaccines, demonstrate that the use of the SARS-CoV-2 glycoprotein S as an antigen allows to form the highest level of protection. Due to the constant change in circulating variants of the SARS-CoV-2 virus, the decrease in the effectiveness of the vaccines with the original antigen composition against new variants of the virus and the continuing high incidence of COVID-19, it is necessary to continuously monitor the effectiveness of vaccines against new variants of the virus and promptly update the antigen composition of vaccines when a decrease in effectiveness is detected.

Strategic and Technical Considerations in Manufacturing Viral Vector Vaccines for the Biomedical Advanced Research and Development Authority Threats.

Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future pandemics. Viral vectors can be an important tool in the repertoire of technologies available to develop effective vaccines against new and emerging infectious diseases. In many instances, vaccines may be needed in a reactive scenario, requiring technologies than can elicit rapid and robust immune responses with a single dose. Here, we discuss how viral vector vaccines are utilized in a vaccine portfolio for priority biological threats, some of the challenges in manufacturing viral vector vaccines, the need to strengthen live virus manufacturing capabilities, and future opportunities to capitalize on the use of viral vectors to improve the sustainability of the Biomedical Advanced Research and Development Authority's vaccine portfolio.

Different COVID-19 vaccines and their respective technological platforms: systematic review of clinical trials

Introduction: The COVID-19 pandemic has highlighted the importance of vaccination in reducing severe cases and deaths. However, the emergence of new SARS-CoV-2 variants raises concerns about the efficacy and safety of available vaccines, mainly due to the diversity of technological platforms used in their development. Objectives: To elucidate the current knowledge about the main vaccine against COVID-19 and their respective technological platforms, licensed and in the licensing phase. Methods: Systematic review according to the PRISMA statement of articles published from 2020, through the PubMed database. Results: The search resulted in fifty studies, of which twenty-one were included. Clinical trials addressed vaccines that use mRNA platforms (n=4), non-replicant viral vector (n=3), attenuated virus (n=2), inactivated vaccine (n=1), recombinant protein nanoparticles (n=3), vaccine using virus-like particles (n=1), subunit vaccine (n=1), DNA vaccine (n=1). Most of the vaccines showed good tolerability and induced neutralizing antibodies against various variants of SARS-CoV-2. Conclusions: Except for the non-replicant viral vector vaccine, intranasal ChAdOx1 nCoV-19 that did not induce mucosal and systemic immune responses, and the DNA vaccine, which induced only a good cellular response, the other vaccines demonstrated good tolerability and efficacy in inducing immune responses.

Serological insights from SARS-CoV-2 heterologous prime and boost responses in Thailand

During the COVID-19 pandemic, heterologous vaccination strategies were employed to alleviate the strain on vaccine supplies. The Thailand Ministry of Health adopted these strategies using vector, inactivated, and mRNA vaccines. However, this approach has introduced challenges for SARS-CoV-2 sero-epidemiology studies. Our study analysed 647 samples from healthcare workers who received CoronaVac, ChAdOx1 nCoV-19, and BNT162b2 vaccines. The serological profile encompassed responses to various SARS-CoV-2 variants and vectors, measuring IgG, IgM, and IgA isotypes, alongside IgG avidity assays. The results demonstrated that heterologous CoronaVac/ChAdOx1 nCoV-19 schedules elicited significantly stronger antibody responses compared to homologous schedules (IgG: 1.2-fold, IgM: 10.9-fold, IgA: 3.1-fold increase). Additionally, a heterologous BNT162b2 boost at 4-weeks post-initial vaccination showed greater antibody levels than a ChAdOx1 nCoV-19 boost (IgG: 1.1-fold, IgM: slight decrease, IgA: 1.5-fold increase). Using a combination of three analytes, IgG against wild-type Spike trimer, nucleoprotein and Omicron receptor binding domains, enabled the clustering of responses within a statistical Gaussian mixture model that successfully discriminates between breakthrough infections and vaccination types (F-score = 0.82). The development of statistical models to predict breakthrough infections can improve serological surveillance. Overall, our study underscores the necessity for vaccine (re-)development and the creation of serological tools to monitor vaccine performance.

A gram-positive enhancer matrix particles vaccine displaying swine influenza virus hemagglutinin protects mice against lethal H1N1 viral challenge.

Animal influenza viruses pose a danger to the general public. Eurasian avian-like H1N1 (EA H1N1) viruses have recently infected humans in several different countries and are often found in pigs in China, indicating that they have the potential to cause a pandemic. Therefore, there is an urgent need to develop a potent vaccine against EA H1N1. In this study, we report the effective intramuscular (i.m.) and/or intranasal (i.n.) vaccination of mice with a subunit influenza vaccine utilizing safe adjuvant gram-positive enhancer matrix (GEM) particles derived from the food-grade bacterium Lactococcus lactis. The hemagglutinin (HA)-protein anchor (PA) subunit vaccine can be simply mixed with GEM particles to produce vaccines. After two booster injections, the i.m.+i.n. administered GEM subunit vaccine achieved hemagglutination inhibition titers in the serum that were equivalent to those observed using the conventional i.m. method. The mucosal and Th1-biased immune responses generated by the i.m. administered subunit vaccine alone were inferior to those induced by the i.n. and i.m.+i.n. administered subunit vaccines. Vaccinated mice were challenged with live viruses (G4 EA H1N1 and A/PR/8/34) to determine whether the adjuvant combination protected against the virus after vaccination with the influenza subunit vaccine. Compared to mice inoculated with HA alone, mice immunized with i.m.+i.n. or i.n. HA-PA-GEM displayed undetectable viral titers in the lungs, at 5 d after challenge. Overall, this study not only offers other potential platforms for the generation of swine influenza vaccines, but also a theoretical foundation for vaccine vector platforms that can be utilized for future research on other infections.

Specific Immune Responses and Oncolytic Effects Induced by EBV LMP2A-Armed Modified Ankara-Vaccinia Virus Vectored Vaccines in Nasopharyngeal Cancer.

The Epstein-Barr virus (EBV) is intricately linked to a range of human malignancies, with EBV latent membrane protein 2A (LMP2A) emerging as a potential target antigen for immunotherapeutic strategies in the treatment of nasopharyngeal carcinoma (NPC). The modified vaccinia virus Ankara (MVA) is universally used in vector vaccine research because of its excellent safety profile and highly efficient recombinant gene expression. Here, we constructed a novel MVA-LMP2A recombinant virus and investigated its specific immune response induction and oncolytic effect. An immunization dose of 2 × 107 PFU induced the highest specific immune response, which was no longer increased by boost injections after four doses. Three weeks post-final immunization, the specific immune response reached its peak. The MVA-LMP2A vaccine-induced LMP2A-specific cytotoxic T lymphocytes (CTLs), which exhibited substantial efficacy against target cells and effectively inhibited tumor growth. Thus, the MVA-LMP2A recombinant virus effectively induces strong LMP2A-specific cellular and humoral immune responses and anti-tumor activity. This work provides a promising therapeutic strategy for developing NPC candidate vaccines, as well as a reference for the treatment of EBV LMP2-associated malignancies.