VaccinesPub Date : 2024-09-27DOI: 10.3390/vaccines12101111
Wayne D Harshbarger, Genevieve Holzapfel, Nishat Seraj, Sai Tian, Chelsy Chesterman, Zongming Fu, Yan Pan, Claire Harelson, Dongjun Peng, Ying Huang, Sumana Chandramouli, Enrico Malito, Matthew James Bottomley, James Williams
{"title":"Structures of the Varicella Zoster Virus Glycoprotein E and Epitope Mapping of Vaccine-Elicited Antibodies.","authors":"Wayne D Harshbarger, Genevieve Holzapfel, Nishat Seraj, Sai Tian, Chelsy Chesterman, Zongming Fu, Yan Pan, Claire Harelson, Dongjun Peng, Ying Huang, Sumana Chandramouli, Enrico Malito, Matthew James Bottomley, James Williams","doi":"10.3390/vaccines12101111","DOIUrl":"https://doi.org/10.3390/vaccines12101111","url":null,"abstract":"<p><p><b>Background:</b> Varicella zoster virus (VZV) is the causative agent for chickenpox and herpes zoster (HZ, shingles). HZ is a debilitating disease affecting elderly and immunocompromised populations. Glycoprotein E (gE) is indispensable for viral replication and cell-to-cell spread and is the primary target for anti-VZV antibodies. Importantly, gE is the sole antigen in Shingrix, a highly efficacious, AS01<sub>B</sub>-adjuvanted vaccine approved in multiple countries for the prevention of HZ, yet the three-dimensional (3D) structure of gE remains elusive. <b>Objectives</b>: We sought to determine the structure of VZV gE and to understand in detail its interactions with neutralizing antibodies. <b>Methods</b>: We used X-ray crystallography and cryo-electron microscopy to elucidate structures of gE bound by recombinant Fabs of antibodies previously elicited through vaccination with Zostavax, a live, attenuated vaccine. <b>Results</b>: The 3D structures resolve distinct central and C-terminal antigenic domains, presenting an array of diverse conformational epitopes. The central domain has two beta-sheets and two alpha helices, including an IgG-like fold. The C-terminal domain exhibits 3 beta-sheets and an Ig-like fold and high structural similarity to HSV1 gE. <b>Conclusions</b>: gE from VZV-infected cells elicits a human antibody response with a preference for the gI binding domain of gE. These results yield insights to VZV gE structure and immunogenicity, provide a framework for future studies, and may guide the design of additional herpesvirus vaccine antigens. <b>Teaser:</b> Structures of varicella zoster virus glycoprotein E reveal distinct antigenic domains and define epitopes for vaccine-elicited human antibodies.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinesPub Date : 2024-09-27DOI: 10.3390/vaccines12101110
Kyung-Jin Min, Yung-Taek Ouh, Sangrak Bae, Yong-Bae Ji, Jae-Kwan Lee, Jae-Weon Kim, Kwang-Jae Cho, Dong-Hun Im
{"title":"Position Statement about Gender-Neutral HPV Vaccination in Korea.","authors":"Kyung-Jin Min, Yung-Taek Ouh, Sangrak Bae, Yong-Bae Ji, Jae-Kwan Lee, Jae-Weon Kim, Kwang-Jae Cho, Dong-Hun Im","doi":"10.3390/vaccines12101110","DOIUrl":"https://doi.org/10.3390/vaccines12101110","url":null,"abstract":"<p><p>Given the rising incidence of human papillomavirus (HPV)-related diseases, including cervical, penile, and oropharyngeal cancers, particularly among men, the implementation of comprehensive HPV vaccination strategies is necessary in South Korea. This position statement advocates the introduction of gender-neutral vaccination (GNV) in the country. It recommends the administration of the HPV vaccine to both men and women aged 9-26 years to prevent a broad spectrum of HPV-related conditions. Specifically, individuals aged 9-14 years are advised to receive two doses of the vaccine, whereas those aged 15-26 years are advised to receive three doses. The optimal age for vaccination is identified as 11-12 years old. Additionally, this statement recommends that women aged 27 years and older be vaccinated based on the discretion of healthcare providers. The introduction of GNV is essential to curb the spread of HPV and reduce the overall burden of HPV-related cancers, making it a critical public health initiative in Korea.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinesPub Date : 2024-09-27DOI: 10.3390/vaccines12101109
Suad Hannawi, Alaa Abuquta, Linda Saf Eldin, Aala Hassan, Ahmad Alamadi, Cuige Gao, Adam Abdul Hakeem Baidoo, Xinjie Yang, Huo Su, Jinxiu Zhang, Liangzhi Xie
{"title":"Immunogenicity and Safety of Omicron-Containing Multivalent COVID-19 Vaccines in Unvaccinated and Previously Vaccinated Adults.","authors":"Suad Hannawi, Alaa Abuquta, Linda Saf Eldin, Aala Hassan, Ahmad Alamadi, Cuige Gao, Adam Abdul Hakeem Baidoo, Xinjie Yang, Huo Su, Jinxiu Zhang, Liangzhi Xie","doi":"10.3390/vaccines12101109","DOIUrl":"https://doi.org/10.3390/vaccines12101109","url":null,"abstract":"<p><p>The SARS-CoV-2 evolution trajectory remains uncertain, and the antigenic characteristics of future variants are highly unpredictable. We report the immunogenicity and safety of multivalent COVID-19 vaccines, SCTV01E and SCTV01E-1, against Omicron BA.5. This phase 2 trial randomized 400 adults into two cohorts, 160 unvaccinated (3 doses) and 240 previously vaccinated (2 doses) individuals to receive 30 µg SCTV01E-1 or 30 µg SCTV01E (1:1) between 4 November and 28 November 2022. Among the unvaccinated cohort, day 42 geometric mean fold rises (GMFRs) of neutralizing antibodies (nAb) against Omicron BA.5 were reported to be 12.8× and 20.5× over day 0 for SCTV01E-1 and SCTV01E, respectively. On day 178, both vaccines increased geometric mean titers (GMTs) of nAb against BA.5 following the booster dose compared to pre-booster levels on D150. Similar frequencies of solicited [6.2% (5/81) and 7.6% (6/79)] and unsolicited [11.1% (9/81) and 10.1% (8/79)] adverse events (AEs) were reported in SCTV01E-1 and SCTV01E groups, respectively. Grade 3 or more AEs were < 2% in both vaccine groups [SCTV01E-1: 1.2% (1/81), SCTV01E: 1.3% (1/79)]. In the previously vaccinated cohort, similar GMFRs were reported on day 28 (SCTV01E-1: 9.4× and SCTV01E: 8.7×) over baseline (D0). On day 148, both vaccines showed increased nAb levels with similar GMFRs over D120. Comparable incidences of solicited [13.2% (16/121) and 10.9% (13/119)] and unsolicited [17.4% (21/121) and 10.9% (13/119)] AEs were reported in SCTV01E-1 and SCTV01E groups, respectively. Numerically identical ≥ grade 3 AEs [SCTV01E-1: 1.7% (2/121) and SCTV01E: 1.7% (2/119)] were reported. This trial demonstrates the effectiveness of updated multivalent vaccines with acceptable safety profiles.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinesPub Date : 2024-09-27DOI: 10.3390/vaccines12101106
John Scully, Abu Salim Mustafa, Asma Hanif, Javed H Tunio, Shumaila Nida Javed Tunio
{"title":"Immune Responses to Methicillin-Resistant <i>Staphylococcus aureus</i> Infections and Advances in the Development of Vaccines and Immunotherapies.","authors":"John Scully, Abu Salim Mustafa, Asma Hanif, Javed H Tunio, Shumaila Nida Javed Tunio","doi":"10.3390/vaccines12101106","DOIUrl":"https://doi.org/10.3390/vaccines12101106","url":null,"abstract":"<p><p><i>Staphylococcus aureus</i> (SA) is a major bacterial pathogen and causes a wide range of clinical infections in humans leading to severe outcomes including meningitis, endocarditis, and sepsis. This literature review examines studies on host immune responses after infections with SA and methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and their immune evasion mechanisms. Furthermore, information about vaccines and immunotherapies against SA and MRSA is reviewed. We found promising toxoid vaccine approaches, which deserve further research. We also found support for antitoxin therapies and immunomodulating therapies as high-potential research areas. Although many promising vaccines and immunotherapy candidates have been studied in animal models, more human clinical studies are needed to confirm their long-term safety and efficacy.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinesPub Date : 2024-09-27DOI: 10.3390/vaccines12101108
Ken Matsui, Heidi Anne Hempel, Gloriana Shelton, Rebecca Ocampo, Troy J Kemp, Yuanji Pan, Ligia A Pinto
{"title":"Reproducibility Assessment of Enzyme-Linked Immunosorbent Assays to Detect Anti-HPV16 L1-Specific IgG1, IgG3, IgA, and IgM Antibodies.","authors":"Ken Matsui, Heidi Anne Hempel, Gloriana Shelton, Rebecca Ocampo, Troy J Kemp, Yuanji Pan, Ligia A Pinto","doi":"10.3390/vaccines12101108","DOIUrl":"https://doi.org/10.3390/vaccines12101108","url":null,"abstract":"<p><strong>Background/objectives: </strong>Enzyme-linked immunosorbent assays (ELISAs) have been used to measure anti-human-papillomavirus (HPV) immunoglobulin IgG. The goal of this study was to evaluate the reproducibility of ELISAs measuring different HPV immunoglobulin isotypes, IgG1, 2, 3, and 4, IgA, and IgM, against HPV16.</p><p><strong>Methods: </strong>Seventy-two serum samples collected from participants in the Costa Rica HPV Vaccine Trial (CVT) and immunized with bivalent HPV vaccine (2vHPV) were used for reproducibility assessment. IgG2 and IgG4 levels were too low to be detected. Levels of IgG1, IgG3, IgA, and IgM were measured, and the data were used to calculate intraclass correlation coefficients (ICCs) and coefficients of variation (CVs).</p><p><strong>Results: </strong>CVs were assessed between technicians (12.8-22.7%) and across days (6.2-30.6%). The overall CVs ranged from 7.7-31.1%. IgM ELISA showed higher CVs (15.8-31.1%) than IgG1, IgG3, and IgA (6.2-22.7%). All ICC values were >98.7%. IgG3 was detected in all samples, while IgG1 and IgA had >86.3% detectability and IgM had 62.1% detectability. Pearson correlational analyses between different antibodies all showed significant correlations (<i>p</i> ≤ 0.001), except when comparing IgGs or IgA to IgM (<i>p</i> = 0.29-0.53).</p><p><strong>Conclusions: </strong>Our data showed that these ELISAs are reproducible and detect isotype antibodies to HPV16 L1 across a range of concentrations in 2vHPV-vaccinated participants.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinesPub Date : 2024-09-26DOI: 10.3390/vaccines12101101
Fengge Wang, Lu Zhou, Abram L Wagner, Zixiang Chen, Yihan Lu
{"title":"Cost-Effectiveness of Hepatitis E Vaccination Strategies among Patients with Chronic Liver Diseases in China: A Model-Based Evaluation.","authors":"Fengge Wang, Lu Zhou, Abram L Wagner, Zixiang Chen, Yihan Lu","doi":"10.3390/vaccines12101101","DOIUrl":"https://doi.org/10.3390/vaccines12101101","url":null,"abstract":"<p><p>Hepatitis E virus (HEV) is a leading cause of acute viral hepatitis worldwide, primarily transmitted through contaminated water and food. In patients with chronic liver disease (CLD), HEV infection might worsen the prognosis. This study aimed to evaluate the cost-effectiveness of hepatitis E vaccination strategies in CLD patients. A decision tree-Markov cohort model was used to assess the cost-effectiveness of universal-vaccination, vaccination-following-screening, and no-vaccination strategies in 100,000 CLD patients over their lifetimes, simulating cohorts aged ≥16 years, ≥40 years, and ≥60 years, based on the licensed vaccination ages and typical ages of CLD onset, from a societal perspective. Model parameters were retrieved and estimated from previous publications and government data. The outcomes included HEV-related cases, costs, and the incremental cost-effectiveness ratio (ICER). Compared to no-vaccination, universal-vaccination reduced HEV-related cases by 32.8% to 39.6%, while vaccination-following-screening reduced them by 38.1% to 49.3%. Furthermore, universal-vaccination showed ICERs of USD 6898.33, USD 6638.91, and USD 6582.69 per quality-adjusted life year (QALY) for cohorts aged ≥16, ≥40, and ≥60 years, respectively. Moreover, the vaccination-following-screening strategy significantly enhanced cost-effectiveness, with ICERs decreasing to USD 6201.55, USD 5199.46, and USD 4919.87 per QALY for the cohorts. Additionally, one-way sensitivity analysis identified the discount rate and utility for CLD patients as the key factors influencing ICER. Probabilistic sensitivity analysis indicated the vaccination-following-screening strategy was cost-effective with probabilities of 92.50%, 95.70%, and 95.90% for each cohort. Hepatitis E vaccination in CLD patients costs less than GDP per capita for each QALY gained in China. The vaccination-following-screening strategy may be the optimal option, especially in those over 60 years.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511531/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinesPub Date : 2024-09-26DOI: 10.3390/vaccines12101100
Adthakorn Madapong, Erika M Petro-Turnquist, Richard J Webby, Alison A McCormick, Eric A Weaver
{"title":"Immunity and Protective Efficacy of a Plant-Based Tobacco Mosaic Virus-like Nanoparticle Vaccine against Influenza a Virus in Mice.","authors":"Adthakorn Madapong, Erika M Petro-Turnquist, Richard J Webby, Alison A McCormick, Eric A Weaver","doi":"10.3390/vaccines12101100","DOIUrl":"https://doi.org/10.3390/vaccines12101100","url":null,"abstract":"<p><strong>Background: </strong>The rapid production of influenza vaccines is crucial to meet increasing pandemic response demands. Here, we developed plant-made vaccines comprising centralized consensus influenza hemagglutinin (HA-con) proteins (H1 and H3 subtypes) conjugated to a modified plant virus, tobacco mosaic virus (TMV) nanoparticle (TMV-HA-con).</p><p><strong>Methods: </strong>We compared immune responses and protective efficacy against historical H1 or H3 influenza A virus infections among TMV-HA-con, HA-con protein combined with AddaVax™ adjuvant, and whole-inactivated virus vaccine (Fluzone<sup>®</sup>).</p><p><strong>Results: </strong>Immunogenicity studies demonstrated robust IgG, IgM, and IgA responses in the TMV-HA-con and HA-con protein vaccinated groups, with relatively low induction of interferon (IFN)-γ<sup>+</sup> T-cell responses across all vaccinated groups. The TMV-HA-con and HA-con protein groups displayed partial protection (100% and 80% survival) with minimal weight loss following challenge with two H1N1 strains. The HA-con protein group exhibited 80% and 100% survival against two H3 strains, whereas the TMV-HA-con groups showed reduced protection (20% survival). The Fluzone<sup>®</sup> group conferred 20-100% survival against two H1N1 strains and one H3N1 strain, but did not protect against H3N2 infection.</p><p><strong>Conclusions: </strong>Our findings indicate that TMV-HA and HA-con protein vaccines with adjuvant induce protective immune responses against influenza A virus infections. Furthermore, our results underscore the potential of plant-based production using TMV-like nanoparticles for developing influenza A virus candidate vaccines.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinesPub Date : 2024-09-26DOI: 10.3390/vaccines12101097
Kwangwook Kim, Seo Young Moon, Seungyeon Kim, In-Ohk Ouh, Yookyoung Lee, Heeji Lim
{"title":"Immunogenicity Analysis of Chikungunya Virus DNA Vaccine Based on Mutated Putative N-Linked Glycosylation Sites of the Envelope Protein.","authors":"Kwangwook Kim, Seo Young Moon, Seungyeon Kim, In-Ohk Ouh, Yookyoung Lee, Heeji Lim","doi":"10.3390/vaccines12101097","DOIUrl":"https://doi.org/10.3390/vaccines12101097","url":null,"abstract":"<p><p>Chikungunya fever is a mosquito-borne infectious disease caused by the chikungunya virus (CHIKV). Recently, CHIKV has spread rapidly worldwide, raising global concerns. However, there is only one approved vaccine is available to prevent CHIKV infection; therefore, different platform vaccines development is a public health priority. The CHIKV genome encodes four non-structural polyproteins (nsP1-4) and one structural polyprotein (capsid, envelope 3, envelope 2, 6 K, and envelope 1). Previous studies have shown that N-linked glycans in viral proteins play important roles in regulating immune responses. Accordingly, in this study, we designed four CHIKV DNA vaccine candidates with mutated N-glycosylation sites in the full-length E and E I/II proteins. Our results indicated that immunization of mice with the vaccine elevated the cytokines levels, including IFN-γ, associated with T cell immune response. Furthermore, the truncated E protein with a deleted E III domain (E I/II) exhibited better immunogenicity than the full-length E protein, and N-linked glycosylation of E I/II protein induced a higher cell-mediated immune response. Overall, our study demonstrates that N-linked glycosylation of the E I/II proteins of CHIKV significantly enhances cell-mediated immune responses, laying the foundation for the development of potential vaccination strategies against CHIKV.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
VaccinesPub Date : 2024-09-26DOI: 10.3390/vaccines12101099
Ekaterina Stepanova, Irina Isakova-Sivak, Victoria Matyushenko, Daria Mezhenskaya, Igor Kudryavtsev, Arina Kostromitina, Anna Chistiakova, Alexandra Rak, Ekaterina Bazhenova, Polina Prokopenko, Tatiana Kotomina, Svetlana Donina, Vlada Novitskaya, Konstantin Sivak, Dzhina Karal-Ogly, Larisa Rudenko
{"title":"Safety and Immunogenicity Study of a Bivalent Vaccine for Combined Prophylaxis of COVID-19 and Influenza in Non-Human Primates.","authors":"Ekaterina Stepanova, Irina Isakova-Sivak, Victoria Matyushenko, Daria Mezhenskaya, Igor Kudryavtsev, Arina Kostromitina, Anna Chistiakova, Alexandra Rak, Ekaterina Bazhenova, Polina Prokopenko, Tatiana Kotomina, Svetlana Donina, Vlada Novitskaya, Konstantin Sivak, Dzhina Karal-Ogly, Larisa Rudenko","doi":"10.3390/vaccines12101099","DOIUrl":"https://doi.org/10.3390/vaccines12101099","url":null,"abstract":"<p><strong>Background: </strong>Influenza and SARS-CoV-2 viruses are two highly variable pathogens. We have developed a candidate bivalent live vaccine based on the strain of licensed A/Leningrad/17-based cold-adapted live attenuated influenza vaccine (LAIV) of H3N2 subtype, which expressed SARS-CoV-2 immunogenic T-cell epitopes. A cassette encoding fragments of S and N proteins of SARS-CoV-2 was inserted into the influenza NA gene using the P2A autocleavage site. In this study, we present the results of preclinical evaluation of the developed bivalent vaccine in a non-human primate model.</p><p><strong>Methods: </strong>Rhesus macaques (<i>Macaca mulatta</i>) (n = 3 per group) were immunized intranasally with 7.5 lg EID<sub>50</sub> of the LAIV/CoV-2 bivalent vaccine, a control non-modified H3N2 LAIV or a placebo (chorioallantoic fluid) using a sprayer device, twice, with a 28-day interval. The blood samples were collected at days 0, 3, 28 and 35 for hematological and biochemical assessment. Safety was also assessed by monitoring body weight, body temperature and clinical signs of the disease. Immune responses to influenza virus were assessed both by determining serum antibody titers in hemagglutination inhibition assay, microneutralization assay and IgG ELISA. T-cell responses were measured both to influenza and SARS-CoV-2 antigens using ELISPOT and flow cytometry. Three weeks after the second immunization, animals were challenged with 10<sup>5</sup> PFU of Delta SARS-CoV-2. The body temperature, weight and challenge virus shedding were monitored for 5 days post-challenge. In addition, virus titers in various organs and histopathology were evaluated on day 6 after SARS-CoV-2 infection.</p><p><strong>Results: </strong>There was no toxic effect of the immunizations on the hematological and coagulation hemostasis of animals. No difference in the dynamics of the average weight and thermometry results were found between the groups of animals. Both LAIV and LAIV/CoV-2 variants poorly replicated in the upper respiratory tract of rhesus macaques. Nevertheless, despite this low level of virus shedding, influenza-specific serum IgG responses were detected in the group of monkeys immunized with the LAIV/CoV-2 bivalent but not in the LAIV group. Furthermore, T-cell responses to both influenza and SARS-CoV-2 viruses were detected in the LAIV/CoV-2 vaccine group only. The animals were generally resistant to SARS-CoV-2 challenge, with minimal virus shedding in the placebo and LAIV groups. Histopathological changes in vaccinated animals were decreased compared to the PBS group, suggesting a protective effect of the chimeric vaccine candidate.</p><p><strong>Conclusions: </strong>The candidate bivalent vaccine was safe and immunogenic for non-human primates and warrants its further evaluation in clinical trials.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11511058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of Smallpox Antibody Testing and Surveillance Following Smallpox Vaccination in the Republic of Korea.","authors":"Hwachul Shin, SangEun Lee, Myung-Min Choi, Hwajung Yi, Yoon-Seok Chung","doi":"10.3390/vaccines12101105","DOIUrl":"https://doi.org/10.3390/vaccines12101105","url":null,"abstract":"<p><p><b>Background</b>: Despite its global eradication in 1977, smallpox remains a concern owing to its potential as a biological agent, thereby prompting the ongoing development and utilization of its vaccine. Vaccination with the <i>Vaccinia</i> virus induces immunity against variola virus, the causative agent of smallpox; however, this immunity does not extend to viruses of different genera within the <i>Poxviridae</i> family. In this study, we aimed to assess the efficacy of an enzyme-linked immunosorbent assay (ELISA) method utilizing <i>Vaccinia</i> virus and recombinant A27L antigen for detecting antibodies against smallpox. <b>Methods.</b> An analysis of the serum from 20 individuals pre- and post-vaccination with the CJ strain (CJ50300) revealed neutralizing antibodies, which were confirmed using the plaque reduction neutralization test (PRNT). The ELISA method, validated with a PRNT<sub>50</sub> cut-off value of >4, exhibited a sensitivity and specificity of >95% and was particularly reactive with the inactivated virus. Furthermore, adherence to the smallpox vaccination policy revealed significant differences in <i>Orthopoxvirus</i> antibody levels among 300 individuals of different age groups. These findings highlight the reliability and efficacy of the ELISA method in detecting post-vaccination antibodies and contribute significantly to diagnostic methods to prepare for potential smallpox resurgence and bioterrorism threats.</p>","PeriodicalId":23634,"journal":{"name":"Vaccines","volume":"12 10","pages":""},"PeriodicalIF":5.2,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142509063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}