Vaccine最新文献

{"title":"Development and validation of a standardized human complement serum bactericidal activity assay to measure functional antibody responses to Neisseria gonorrhoeae","authors":"Kathryn A. Matthias ,&nbsp;Alexandra Reveille ,&nbsp;Kumaresh Dhara ,&nbsp;Christopher S. Lyle ,&nbsp;Robert J. Natuk ,&nbsp;Brian Bonk ,&nbsp;Margaret C. Bash","doi":"10.1016/j.vaccine.2024.126508","DOIUrl":"10.1016/j.vaccine.2024.126508","url":null,"abstract":"<div><div>The recent entry of multiple vaccines targeting <em>Neisseria gonorrhoeae</em> (<em>Ng</em>) into the clinical development pathway has highlighted the need to establish methods of adequately assessing anti-gonococcal immune responses. Serum bactericidal activity (SBA) is utilized as a measurement of efficacy in licensure of meningococcal vaccines, but the importance of functional antibodies in preventing and/or clearing gonococcal infections remains largely unknown. In an effort to elucidate the utility of SBA as an immune correlate of protection, we sought to develop a standardized high-throughput human complement SBA (hSBA) assay for which any strain of interest could be tested under uniform conditions, with minimal screening of complement required. Utilization of IgG/IgM-depleted pooled human complement serum permitted testing of diverse serum resistant and sensitive gonococcal and unencapsulated meningococcal strains when bacteria were cultured to induce lipooligosaccharide sialylation; only one of nine randomly selected lots demonstrated intrinsic toxicity. The hSBA assay was well suited for use with multiple test serum sources, including rabbit, mouse, and human serum samples, suggesting widespread applicability.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126508"},"PeriodicalIF":4.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645320","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":"Immunogenicity and protection of a triple repeat domain III mRNA vaccine against Zika virus","authors":"Yu-Sun Lee ,&nbsp;Mi Sun Cheong ,&nbsp;Jisun Lee ,&nbsp;Eun-Kyoung Bang ,&nbsp;Sang In Park ,&nbsp;Hyo-Jung Park ,&nbsp;Seo-Hyeon Bae ,&nbsp;Subin Yoon ,&nbsp;Gahyun Roh ,&nbsp;Seonghyun Lee ,&nbsp;Youngran Cho ,&nbsp;Dahyeon Ha ,&nbsp;Ayoung Oh ,&nbsp;Soo-Yeon Lee ,&nbsp;Eun-Jin Choi ,&nbsp;Huijeong Choi ,&nbsp;Sohee Jo ,&nbsp;Yeeun Lee ,&nbsp;Jungmin Kim ,&nbsp;Hye Won Kwak ,&nbsp;Wonil Kim","doi":"10.1016/j.vaccine.2024.126518","DOIUrl":"10.1016/j.vaccine.2024.126518","url":null,"abstract":"<div><div>Zika virus (ZIKV) infection is primarily transmitted by mosquitoes and often asymptomatic in most individuals. Infection during pregnancy can lead to severe birth defects such as congenital microcephaly, and currently, there is no approved vaccine for ZIKV. Several studies are investigating the development of ZIKV vaccine using DNA and RNA as well as recombinant protein technologies; however, the outcomes thus far have not been consistently noteworthy. In this study, we designed an mRNA vaccine for ZIKV and evaluated its immunogenicity using a mouse model. Our vaccine, termed 3xEIII, encodes a triple repeat of domain III from the ZIKV E protein. We effectively encapsulated the mRNA within lipid nanoparticles (LNPs), administered 3xEIII to mice via two intramuscular injections, and assessed the induced humoral and cellular immune responses. Specifically, the vaccine elicited neutralizing antibodies that effectively eliminated ZIKV from the organs of challenged mice. Notably, 3xEIII conferred both protective effects and long-term immunity. In subsequent challenges conducted 40 weeks after boosting, immunized mice experienced temporary weight loss but showed significantly reduced viral titers in target organs by the 9th day post-infection. Conclusively from these findings, 3xEIII stands out as a promising noteworthy mRNA vaccine candidate for Zika virus.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126518"},"PeriodicalIF":4.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640542","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":"Live-attenuated vaccine failure after liver transplantation: A 20-year cohort study","authors":"Munehiro Furuichi ,&nbsp;Takuma Ohnishi ,&nbsp;Mizuki Yaginuma ,&nbsp;Yohei Yamada ,&nbsp;Ken Hoshino ,&nbsp;Tetsuo Nakayama ,&nbsp;Masayoshi Shinjoh","doi":"10.1016/j.vaccine.2024.126527","DOIUrl":"10.1016/j.vaccine.2024.126527","url":null,"abstract":"<div><h3>Background</h3><div>A recent conditional recommendation suggests considering live-attenuated vaccines for solid organ transplant recipients, yet the conditions of their safe and effective administration remain unclear.</div></div><div><h3>Methods</h3><div>This prospective study was conducted at Keio University Hospital from 2002 to August 2023. We gave a live-attenuated vaccine to liver transplant (LT) recipients fulfilling criteria for live-attenuated vaccines, including criteria for humoral and cell-mediated immunity. Patient background information, immunization date, vaccine strain, immunosuppressive agents at the time of vaccination, and antibody titers were collected. Factors related to primary and secondary vaccine failure were evaluated to enhance the effectiveness of the live-attenuated vaccine program after LT.</div></div><div><h3>Results</h3><div>Among 67 LT recipients, 54, 55, 47, and 55 received at least one dose of live-attenuated vaccine for measles, rubella, varicella, and mumps, respectively. The difference in vaccine strains, but not the use of two or more immunosuppressive agents, was associated with a lower risk of vaccine failures. Measles vaccine with the AIK-C strain exhibited significantly lower primary and secondary failure rates than the CAM-70 strain (1/38 vs. 4/16, odds ratio: 0.08, 95 % confidence interval [CI]: 0.01–0.80, <em>p</em> = 0.02, and hazard ratio: 0.54, 95 % CI: 0.34–0.85, <em>p</em> = 0.01, respectively). No primary failures were observed with the TO-336 strain of rubella, whereas 4 of 10 LT recipients with the Matsuura strain of rubella did not seroconvert. For mumps, the Hoshino strain showed lower primary failure rates than the Torii strain (15/52 vs. 3/3, <em>p =</em> 0.03).</div></div><div><h3>Conclusion</h3><div>According to a 20-year long-term study, vaccine strains are the most critical factor influencing primary and secondary vaccine failure in post-transplant live-attenuated vaccination.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126527"},"PeriodicalIF":4.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640541","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 a candidate vaccine against severe fever with thrombocytopenia syndrome virus using Gn/Gc glycoprotein via multiple expression vectors delivered by attenuated Salmonella confers effective protection in hDC-SIGN transduced mice","authors":"Ji-Young Park,&nbsp;Amal Senevirathne,&nbsp;John Hwa Lee","doi":"10.1016/j.vaccine.2024.126524","DOIUrl":"10.1016/j.vaccine.2024.126524","url":null,"abstract":"<div><div>In this study, we developed two plasmid constructs, pJHL270 and pJHL305, for the dual expression of Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) Gn and Gc glycoproteins in both prokaryotic and eukaryotic systems. The constructs feature a prokaryotic expression controlled by the Ptrc promoter and a eukaryotic expression driven by the cytomegalovirus promoter and Semliki Forest Virus RNA-dependent RNA polymerase. The Gn/Gc antigenic epitope was derived from consensus sequences of 12 SFTSV M segments collected in South Korea and designed for optimal antigen expression. The full antigen was expressed eukaryotically for post-translational modifications, while the epitope construct was expressed prokaryotically. These constructs were electroporated into an attenuated <em>Salmonella Typhimurium</em> strain (JOL2500) for plasmid delivery, resulting in JOL3042 and JOL3045. Successful expression was confirmed via qRT-PCR and western blot analysis. Mice immunized with JOL3042 showed antibody responses as early as two weeks, while JOL3045 elicited responses at six weeks, skewed toward a Th1 response initially, later balancing with Th2. Flow cytometry revealed significant CD3⁺CD4⁺ and CD3⁺CD8⁺ T-cell responses. Both constructs generated neutralizing antibodies, and a challenge study indicated significant reductions in viral loads in the serum, liver, and spleen of vaccinated mice, demonstrating the effectiveness of the <em>Salmonella</em>-mediated delivery system against SFTSV infection. The outcome of the current study may pave the way to develop a safer and more effective <em>Salmonella-mediated</em> vaccine against lethal SFTSV infection in vulnerable populations.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126524"},"PeriodicalIF":4.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) meeting, virtual gathering, 10–13 September 2024","authors":"Philipp Lambach ,&nbsp;Sheetal Silal ,&nbsp;Alyssa N. Sbarra ,&nbsp;Mitsuki Koh ,&nbsp;Rakesh Aggarwal ,&nbsp;Habib Hasan Farooqui ,&nbsp;Stefan Flasche ,&nbsp;Alexandra B. Hogan ,&nbsp;Sun-Young Kim ,&nbsp;Kathy Leung ,&nbsp;William J. Moss ,&nbsp;Patrick K. Munywoki ,&nbsp;Allison Portnoy ,&nbsp;Meru Sheel ,&nbsp;Xuan-Yi Wang","doi":"10.1016/j.vaccine.2024.126519","DOIUrl":"10.1016/j.vaccine.2024.126519","url":null,"abstract":"<div><div>The Immunization and Vaccines-related Implementation Research Advisory Committee (IVIR-AC) is the primary advisory body of the World Health Organization conducting independent reviews of immunization-related implementation research, with a primary focus on transmission and economic modeling analyses that estimate the value and impact of vaccines. From 10 to 13th September 2024, IVIR-AC convened virtually for its second of two semi-annual meetings to provide feedback and recommendations across six sessions including: pneumococcal vaccination strategies that rely on indirect protection; vaccine impact modeling for chikungunya; The Lancet Commission on strengthening the use of epidemiological modeling of emerging and pandemic infectious diseases; methods for immunization coverage estimation; setting immunization research priorities in the South-East Asian Region; and modeling evidence related to typhoid conjugate vaccine schedules. This report summarizes the sessions, proceedings, and recommendations from that meeting.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126519"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635268","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":"A three antigen hepatitis B vaccine induces T cells to Pres1 and Pres2 which correlate with anti HBs antibody titers: An investigation into the immunological mechanisms contributing to high anti-HBs titers","authors":"Tamara K. Berthoud ,&nbsp;Tanvir Ahmed ,&nbsp;Warner Nadia ,&nbsp;Illia Petrov ,&nbsp;Lanjian Yang ,&nbsp;Danni Colledge ,&nbsp;Rachel Hammond ,&nbsp;Catalina Soare ,&nbsp;Barthelemy Ontsouka ,&nbsp;Daniel Plaskin ,&nbsp;David E. Anderson ,&nbsp;Francisco Diaz-Mitoma","doi":"10.1016/j.vaccine.2024.126513","DOIUrl":"10.1016/j.vaccine.2024.126513","url":null,"abstract":"<div><div>PreHevbrio® is a 3-antigen HBV vaccine (3-A-HBV) engineered to express the three HBV envelope proteins; the small ‘S' hepatitis B surface antigen (SHBs or HBsAg), the middle pre-S2 + HBsAg (MHBs) and the large PreS1 + PreS2 + HBsAg (LHBs) antigens. 3-A-HBV has been shown to induce superior and more durable antibody responses relative to a 1-A-HBV despite containing half the ‘S' antigen dose. To explain the mechanism(s) behind the high immunogenicity, the potential influence of mammalian glycosylation, HBs antigen conformation, anti-HBs epitope binding profiles and T-cell responses to the PreS antigens were investigated.</div><div>In this paper, we demonstrate that glycosylation status does not play a role in the increased immunogenicity of the 3-A-HBV, but that the 3-A-HBV particles are able to induce T cell responses to PreS1 and PreS2 antigens. Epitope mapping demonstrated that the 3-A-HBV particles are inherently more antigenic than 1-A-HBV particles, leading to quantitative differences in the anti-HBs antibody response. Further, we demonstrate that the T cell responses significantly correlate with the higher observed anti-HBs titers and may contribute to the higher and more durable anti-HBs titers.</div><div>This trial is registered at <span><span>Clinicaltrials.gov</span><svg><path></path></svg></span> (<span><span>NCT03393754</span><svg><path></path></svg></span>) and EudraCT (2017–001819-36).</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126513"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety and immunogenicity of the Ad26/protein preF RSV vaccine in adults aged 18 to 59 years with and without at-risk comorbidities for severe respiratory syncytial virus disease: A phase 3, randomized, controlled, immunobridging trial","authors":"Archana Jastorff ,&nbsp;Efi Gymnopoulou ,&nbsp;Jose Salas ,&nbsp;Elizabeth Merrall ,&nbsp;Erik Buntinx ,&nbsp;Charlotte Martin ,&nbsp;Helena H. Askling ,&nbsp;Isabelle Schenkenberger ,&nbsp;Angela Cano Yuste ,&nbsp;William Smith ,&nbsp;Roberto Sotolongo ,&nbsp;Charlotte Von Engelhardt ,&nbsp;Arangassery Rosemary Bastian ,&nbsp;Christy Comeaux ,&nbsp;Nynke Ligtenberg ,&nbsp;Benoit Callendret ,&nbsp;Esther Heijnen","doi":"10.1016/j.vaccine.2024.126514","DOIUrl":"10.1016/j.vaccine.2024.126514","url":null,"abstract":"<div><h3>Background</h3><div>Respiratory syncytial virus (RSV) causes a significant disease burden in adults with chronic comorbidities. Rates of severe RSV disease and death are as high, or higher in younger adults with risk factors than in healthy older adults in whom RSV vaccination is recommended. We conducted an immunobridging study using the Ad26/protein RSV preF vaccine, which previously demonstrated efficacy in adults aged ≥65 years to support extrapolation of efficacy demonstrated in an older population to younger adult populations at high risk of severe RSV disease.</div></div><div><h3>Methods</h3><div>This Phase 3 randomized, double-blind, placebo-controlled trial assessed the safety/tolerability and immunogenicity of Ad26/protein preF RSV in adults aged 18–59 years without (Cohort 1) and with (Cohort 2) chronic cardiac or pulmonary comorbidities, compared to adults aged ≥65 years (Cohort 3) in whom efficacy against RSV disease was demonstrated. Humoral and cellular immune responses were assessed at baseline, Days 15 and 183. Reactogenicity and safety were assessed in all participants.</div></div><div><h3>Results</h3><div>1118 participants were enrolled (Cohort 1: 387; Cohort 2: 388; Cohort 3: 343). Compared to adults aged ≥65 years RSV neutralizing antibody titers were non-inferior in adults aged 18–59 years, including those at high risk. Levels of pre-F A IgG antibodies and frequencies of RSV-F specific interferon-gamma T-cells increased by Day 15 post-vaccination, and remained above baseline for at least 6 months in all cohorts. Reactogenicity and safety were clinically acceptable but age-dependent, with higher rates of Grade 3 systemic adverse events in adults aged 18–59-years than adults ≥65 years.</div></div><div><h3>Conclusion</h3><div>Ad26/protein preF RSV vaccine induced robust humoral and cellular immune responses in adults aged 18–59 years with or without chronic cardiac or pulmonary comorbidities, of similar magnitude to responses in older adults, allowing inference of efficacy and protection against RSV-associated respiratory disease in this population. <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span> <span><span>NCT05070546</span><svg><path></path></svg></span></div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126514"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142633835","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":"Vaccine spillover effects in Africa: A cross-national study of vaccine spillover and confidence in Kenya, Nigeria, and South Africa","authors":"Alee Lockman ,&nbsp;Timothy Callaghan ,&nbsp;Christine Crudo Blackburn ,&nbsp;Brian Colwell","doi":"10.1016/j.vaccine.2024.126528","DOIUrl":"10.1016/j.vaccine.2024.126528","url":null,"abstract":"<div><h3>Background</h3><div>Vaccine hesitancy and a distrust of the COVID-19 vaccine is widespread in many African nations, stemming from historic medical abuses and low confidence in governments. While studies have examined drivers of vaccine hesitancy in Africa, little is known about vaccine spillover effects: how prior experiences with vaccines influence individuals' confidence in vaccines and future vaccination behaviors.</div></div><div><h3>Methods</h3><div>In a large online survey conducted across three African countries (Kenya, <em>N</em> = 1545; Nigeria, <em>N</em> = 1557; South Africa, <em>N</em> = 1588), we examined five measures of vaccine spillover: how experiences with the COVID-19 vaccination process influenced respondents' confidence in the safety, efficacy, and importance of all vaccines approved for use in their country, and the likelihood of vaccinating themselves or their children in the future. Multivariate binary logistic regression analyses were conducted to determine factors associated with each of the five outcome measures.</div></div><div><h3>Results</h3><div>Large numbers of individuals in all three countries experienced positive vaccine spillover: becoming more likely to vaccinate in the future and experiencing greater confidence in vaccines, due to their prior experiences with the COVID-19 vaccination process. The highest positive spillover effects were observed in Kenya, with 71 % reporting a greater likelihood of vaccinating themselves in the future, compared to just 60.1 % of Nigerian respondents and 51.7 % of South African respondents. Multivariate models provide evidence that demographic correlates of positive vaccine spillover vary across nations; however, prior vaccination, misinformation endorsement, and confidence in government both consistently predict spillover in all three nations.</div></div><div><h3>Conclusion</h3><div>These findings suggest that while drivers of vaccine spillover are country specific, strategies to address COVID-19 misinformation and to strengthen individuals' trust in government may help facilitate greater vaccine uptake in the future.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126528"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatal ascending paralysis after typhoid vaccine: Guillain and Barré's description of the very first case","authors":"Eelco F.M. Wijdicks","doi":"10.1016/j.vaccine.2024.126443","DOIUrl":"10.1016/j.vaccine.2024.126443","url":null,"abstract":"<div><div><em>Background:</em> Albeit rare, Guillain - Barré syndrome (GBS) has been associated with several vaccines. Surveys of these associations have not looked before 1950. Herein, I revisit the first described case of vaccine-associated GBS, manifesting during the Great War and to prevent typhoid.</div><div><em>Methods:</em> Review of primary and secondary source material. Description of a landmark case.</div><div><em>Results:</em> Review of a report of a 31-year-old brigadier who was revaccinated with “vaccin TAB” (a triple antityphoid-paratyphoid vaccine A and B) which days later was followed by rapid progression of limb weakness, oropharyngeal weakness and fatal neuromuscular respiratory weakness. Cerebrospinal fluid showed mild pleocytosis and increased protein (albumen). There was a normal brain and spinal cord at autopsy.</div><div><em>Conclusion:</em> This is the first reported case of a vaccine-associated GBS<em>.</em></div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"42 26","pages":"Article 126443"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intranasal immunization with CPAF combined with ADU-S100 induces an effector CD4 T cell response and reduces bacterial burden following intravaginal infection with Chlamydia muridarum","authors":"Taylor B. Poston ,&nbsp;Jenna Girardi ,&nbsp;Marie Kim ,&nbsp;Peter Zwarycz ,&nbsp;A. Grace Polson ,&nbsp;Kacy S. Yount ,&nbsp;Courtne Hanlan ,&nbsp;Ian Jaras Salas ,&nbsp;Sarah Mae Lammert ,&nbsp;Daisy Arroyo ,&nbsp;Tony Bruno ,&nbsp;Manhong Wu ,&nbsp;James Rozzelle ,&nbsp;Jeff Fairman ,&nbsp;Aaron P. Esser-Kahn ,&nbsp;Toni Darville","doi":"10.1016/j.vaccine.2024.126526","DOIUrl":"10.1016/j.vaccine.2024.126526","url":null,"abstract":"<div><div><em>Chlamydia trachomatis</em> (Ct) is the most common bacterial sexually transmitted infection globally, and a vaccine is urgently needed to stop transmission and disease. Chlamydial Protease Activity Factor (CPAF) is an immunoprevalent and immunodominant antigen for CD4 T cells and B cells, which makes it a strong vaccine candidate. Due to the tolerogenic nature of the female genital tract (FGT) and its lack of secondary lymphoid tissue, effective induction of protective cell-mediated immunity will likely require potent and safe mucosal adjuvants. To address this need, we produced CPAF in a cell-free protein synthesis platform and adjuvanted it with the TLR9-agonist CpG1826, a synthetic cyclic-di-AMP (CDA) STING (stimulator of interferon genes) agonist ADU-S100, and/or the squalene oil-in-water nanoemulsion, AddaS03. We determined that intranasal immunization with CPAF plus ADU-S100 was well tolerated in female mice, induced CD4 T cells characterized by TNFα production alone or in combination with IL-17 A or IFNγ, significantly reduced bacterial shedding, and shortened the duration of infection in mice intravaginally challenged with <em>Chlamydia muridarum</em>. These data demonstrate the potential for CDA as a mucosal adjuvant for vaccines against Chlamydia genital tract infection.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"43 ","pages":"Article 126526"},"PeriodicalIF":4.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142635672","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}