Vaccine最新文献

{"title":"A novel SARS-CoV-2 mRNA virus-like particle vaccine is highly potent and well tolerated in adults in a phase 1 randomized clinical trial","authors":"Temitope Oyedele ,&nbsp;Rachel Park ,&nbsp;Kelly Morales ,&nbsp;Manish Jain ,&nbsp;Lawrence Sher ,&nbsp;Apinya Vutikullird ,&nbsp;Abby Isaacs ,&nbsp;Brett Jepson ,&nbsp;Kathryn Shoemaker ,&nbsp;Ann Marie Stanley ,&nbsp;Joseph Lee ,&nbsp;Cindy Handelsman ,&nbsp;Stacey Cromer Berman ,&nbsp;Lee-Jah Chang","doi":"10.1016/j.vaccine.2026.128304","DOIUrl":"10.1016/j.vaccine.2026.128304","url":null,"abstract":"<div><h3>Background</h3><div>The need for SARS-CoV-2 vaccines with improved potency, lower reactogenicity, broader coverage, and prolonged protection persists. We examined the safety and immunogenicity of two ferritin scaffold-based self-assembling SARS-CoV-2 mRNA virus-like particle (VLP) vaccines.</div></div><div><h3>Methods</h3><div>In this, randomized, Phase I, open-label, active-controlled study (<span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span> <span><span>NCT06147063</span><svg><path></path></svg></span>) participants received a single 5 μg or 10 μg intramuscular injection of AZD9838 (BA.4/5 variant) or AZD6563 (XBB.1.5 variant), or 30 μg BNT162b2, a licensed mRNA vaccine (XBB.1.5 variant).</div><div>The primary safety endpoint was the incidence of solicited adverse reactions (ARs) through Day 8, unsolicited adverse events (AEs) through Day 29, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) through Day 361. The primary immunogenicity endpoint was to characterize the neutralizing antibody (nAb) responses to the ancestral and Omicron (BA.4/5, XBB.1.5) variants at Day 29; characterization of nAb response to Omicron JN.1 was an exploratory analysis.</div></div><div><h3>Results</h3><div>In total, 166 participants aged 18–64 years and 76 participants ≥65 years of age were vaccinated. AZD9838 and AZD6563 were well-tolerated at both dosages. Overall, fewer solicited ARs were reported with AZD9838 and AZD6563 versus BNT162b2. Unsolicited AEs were similar between groups; no related SAEs, AESIs, or MAAEs were reported to Day 180.</div><div>Day 29 nAb GMTs were higher following 10 μg AZD6563 versus 5 μg and higher than AZD9838 across variants and age groups, remaining above baseline and similar to BNT162b2 at Day 180; 10 μg AZD6563 resulted in nAb GMTs similar to BNT162b2 in both age groups.</div></div><div><h3>Conclusion</h3><div>By combining mRNA vaccine technology with VLP-based antigen display, we developed two candidate SARS-CoV-2 vaccines, AZD9838 and AZD6563, that were well tolerated versus a licensed mRNA vaccine, BNT162b2. Furthermore, the variant-matched AZD6563 generated a similar immunogenicity to BNT162b2 but at one third of the dosage (10 μg versus 30 μg).</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128304"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146145175","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":"Vaccination under sedation in children with needle phobia or behavioural difficulties: A retrospective study.","authors":"Deidre Brogan ,&nbsp;Prathiyankara Shailendra Prabhu ,&nbsp;Lucy Deng ,&nbsp;Ketaki Sharma ,&nbsp;Andrew Dunn ,&nbsp;Ella Sharp ,&nbsp;Clementine David ,&nbsp;Lois Leacey ,&nbsp;Katrina Sterling ,&nbsp;Amber Hooker ,&nbsp;Natalie Ong ,&nbsp;Nicholas Wood ,&nbsp;Kristine Macartney ,&nbsp;Rama Kandasamy","doi":"10.1016/j.vaccine.2026.128352","DOIUrl":"10.1016/j.vaccine.2026.128352","url":null,"abstract":"<div><h3>Background</h3><div>Children and adolescents with conditions such as needle phobia and neurodevelopmental disorders may have difficultly being vaccinated in the community. Assisted vaccination clinics provide tailored support for children with additional needs surrounding routine scheduled vaccine administration. This study evaluates the efficacy of an assisted vaccination clinic, in Australia over a decade.</div></div><div><h3>Methods</h3><div>This was a retrospective cohort study conducted from 2015 to 2024. The participants included children who were referred to the Assisted Vaccination Clinic at the Children's Hospital Westmead following unsuccessful attempts at vaccination in the community. Study data were extracted from electronic medical records and patients' vaccination records reviewed in the Australian Immunisation Register.</div></div><div><h3>Results</h3><div>Between 1 January 2015 and 31 December 2024, 169 patients were seen across 227 clinic visits. The median age was 13.3 years (IQR 11.7–14.9 years). Needle phobia (171/227, 75.3%) and autism spectrum disorder (76/227, 33.5%) were the most frequently reported conditions associated with being seen in the clinic. HPV (70.9%, 161/227), dTpa (62.6%, 142/227), and MenACWY (21.6%, 49/227) were the most frequent vaccines required for administration. Inhaled nitrous oxide 96/227 (42.3%) and oral midazolam 22/227 (9.7%) were the most frequently used pharmacological interventions. Oral lorazepam was used as a pre-hospital medication on 26 occasions. Non-pharmacological interventions were employed to optimise patient comfort in 52% of visits. Successful vaccination occurred in 77.1% (175/227) of visits. Long term follow-up was conducted for 87/170 patients who had subsequently turned 17 years of age, 72/87 (82.8%) had received further vaccines in the community and 58/87 (66.7%) were up-to-date with their scheduled vaccines.</div></div><div><h3>Conclusion</h3><div>Children with needle phobia and/or behavioural difficulties who cannot be vaccinated in the primary care setting may be successfully vaccinated using a tailored sedation service. Vaccine coverage of this group of previously under-vaccinated children managed at this clinic reached that of their peers nationwide.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128352"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146175214","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":"Corrigendum to “Safety and immunogenicity of SpiN-Tec, a T-cell based RBD-Nucleocapsid chimeric vaccine for COVID-19” [Vaccine 64 (2025) 127756]","authors":"Gregório Guilherme Almeida ,&nbsp;Jorge Andrade Pinto ,&nbsp;Patrícia Machado Pinto ,&nbsp;Ludmila Bezerra da Silva ,&nbsp;Luis Adan Flores Andrade ,&nbsp;Bruno Vinícius Santos Valiate ,&nbsp;Nathália Zini ,&nbsp;Flávia Fonseca Bagno ,&nbsp;Graziella Gomes Rivelli ,&nbsp;Karine Lima Lourenço ,&nbsp;Jéssica Pauline Coelho Souza ,&nbsp;Isabela Pereira Gomes ,&nbsp;Natália Salazar de Castro ,&nbsp;Ana Luiza Chaves Maia ,&nbsp;Alex Fiorini de Carvalho ,&nbsp;Júlio Castro Alves ,&nbsp;Júlia Teixeira de Castro ,&nbsp;Guangzhao Li ,&nbsp;Natália Satchiko Hojo-Souza ,&nbsp;Gabriel da Rocha Fernandes ,&nbsp;Helton da Costa Santiago","doi":"10.1016/j.vaccine.2026.128316","DOIUrl":"10.1016/j.vaccine.2026.128316","url":null,"abstract":"","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128316"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146175216","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":"Human papillomavirus (HPV) vaccine coverage and associated sociodemographic factors among individuals eligible for publicly funded vaccine in Ontario, Canada from 2007 to 2023: A Canadian immunization research network study","authors":"Ramandip Grewal ,&nbsp;Jenna Alessandrini ,&nbsp;Sarah E. Wilson ,&nbsp;Alejandro Hernandez ,&nbsp;Nicole E. Basta ,&nbsp;Ann N. Burchell ,&nbsp;Shelley L. Deeks ,&nbsp;Gillian H. Lim ,&nbsp;Christine Navarro ,&nbsp;Gina Ogilvie ,&nbsp;Lauren A. Paul ,&nbsp;Sarah A. Buchan","doi":"10.1016/j.vaccine.2026.128303","DOIUrl":"10.1016/j.vaccine.2026.128303","url":null,"abstract":"<div><div><em>Background</em>: Publicly funded human papillomavirus (HPV) vaccination programs are available for school-aged children to help prevent HPV-associated cancers and other outcomes, with goals of reaching 90% coverage (≥2 doses) in Canada. Since the introduction of gender-neutral programs in Ontario (2016/2017), publicly available coverage estimates by sex and other sociodemographics, particularly throughout the COVID-19 pandemic, have been limited.</div><div><em>Methods</em>: We conducted a population-based cohort study consisting of males and females eligible for publicly funded HPV vaccine programs in Ontario (2007-2023). Using linked vaccination and administrative databases, we estimated vaccine coverage by sex, year, birth cohort, and various sociodemographics. We explored the impacts of the COVID-19 pandemic on coverage by comparing those who first became eligible during pandemic years to those who first became eligible before the pandemic. Multinomial logistic regression was used to report on associations between sociodemographics and vaccination status (unvaccinated, partial vaccination, up-to-date [≥2 doses] vaccination).</div><div><em>Results</em>: Up-to-date coverage varied by birth cohort and sex, ranging from 40-70% among females and 40-66% among males; uptake of at least 1 dose was higher (females:51-77%; males:60-74%). The lowest coverage estimates were among individuals who first became program eligible during the pandemic with some improvement in coverage through catch-up opportunities in later years (i.e., from 3-6% [2019-2021] to 40-51% [2022-2023]). Vaccine coverage, particularly up-to-date vaccination, was associated with socioeconomic status, with individuals in the lowest income neighbourhoods experiencing lower uptake, for example. This trend was most apparent among cohorts who became eligible during pandemic years.</div><div><em>Conclusions</em>: Following inception of gender-neutral publicly funded programs in Ontario, HPV vaccine coverage for females and males has been substantially short of national goals. Findings suggest a need to improve uptake and access to publicly funded catch-up opportunities. Efforts to reduce inequities in vaccine uptake are crucial to reach targets and close the gap in HPV-associated disparities.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128303"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146159841","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":"Willingness to vaccinate in a future pandemic. Evidence from a vignette experiment","authors":"Ádám Stefkovics ,&nbsp;Anna Sára Ligeti ,&nbsp;Júlia Koltai","doi":"10.1016/j.vaccine.2026.128284","DOIUrl":"10.1016/j.vaccine.2026.128284","url":null,"abstract":"<div><div>The COVID-19 pandemic highlighted both the importance of vaccination and the persistent challenge of vaccine hesitancy. As future global outbreaks remain a realistic threat, understanding the factors shaping vaccination intentions beyond the COVID-19 context is crucial. We conducted a pre-registered vignette experiment in an online survey in Hungary (<span><math><mrow><mi>N</mi><mo>=</mo><mn>1000</mn></mrow></math></span>), varying six disease and vaccine-related attributes: disease severity, vaccine’s country of origin, technology, regulatory approval, side effects, and recommendation source. Respondents evaluated eight randomly assigned scenarios each. Multilevel linear models were used to estimate the main and interaction effects of vignette and individual characteristics. Vaccine side effects, approval status, and country of origin were the strongest predictors of willingness to vaccinate in a future pandemic. Respondents were substantially less willing to accept vaccines with stronger side effects or those originating from China, and preferred vaccines jointly approved by Hungarian and European authorities. In contrast, vaccine technology (mRNA vs. non-mRNA) and recommendation source had no significant effect. Less-educated, rural respondents and those unvaccinated against COVID-19 were largely unaffected by differences in vaccine attributes or contextual factors. Concerns over side effects and institutional legitimacy remain central in hypothetical future pandemics, while technological distinctions play a minor role. Strengthening trust through transparent, evidence-based communication, early engagement, and tailored messages addressing the specific concerns of hesitant subgroups not even influenced by disease and vaccine-related factors will be essential to improve vaccine uptake and pandemic preparedness.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128284"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168642","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":"Structural determinants of vaccine access: an integrated review of the Canadian literature","authors":"Muhammad Haaris Tiwana ,&nbsp;Julia Smith","doi":"10.1016/j.vaccine.2026.128324","DOIUrl":"10.1016/j.vaccine.2026.128324","url":null,"abstract":"<div><h3>Background</h3><div>Vaccination is a critical public health tool, yet vaccine uptake in Canada is declining, with persistent inequities among marginalized populations. While individual-level vaccine hesitancy is well studied, there is limited synthesis of how structural determinants such as governance, institutional practices, and cultural norms shape access.</div></div><div><h3>Objective</h3><div>To examine how structural determinants shape vaccine access among marginalized populations in Canada.</div></div><div><h3>Methods</h3><div>We conducted an integrative review following the Joanna Briggs Institute (JBI) methodology and reported according to PRISMA-ScR guidelines. Studies were included if they addressed vaccine access in the Canadian context and examined systemic inequities affecting marginalized populations. Data from 40 sources were charted and analyzed thematically using a structural determinant of health framework, which categorized findings into four domains: (1) values, beliefs, culture, and norms; (2) governance; (3) laws, policies, regulations, and budgets; and (4) institutional practices.</div></div><div><h3>Results</h3><div>Structural determinants affected vaccine access in multiple, intersecting ways. Cultural mistrust, religious concerns, and social norms influenced perceptions of vaccine safety and relevance. Governance issues including top-down strategies, lack of community engagement, and inconsistent communication undermined public trust. Legal and policy barriers, such as identification requirements, excluded marginalized populations. Institutional practices, including inaccessible clinic locations, and absence of race-based data, further contributed to inequities. Positive examples of community- and peer-led interventions were identified but often underfunded or excluded from formal systems.</div></div><div><h3>Conclusions</h3><div>Addressing these barriers requires participatory governance, culturally safe services, and sustained investment in community-led models. Our framework can inform equity-focused vaccine policy and practice in Canada and similar high-income contexts.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128324"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168591","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":"Immunoinformatics design and in vivo evaluation of a multiepitope vaccine targeting OMPL1, Lipl32, Lipl41, and Lipl46 for leptospirosis in a male ICR mouse model","authors":"Ritik Thumar ,&nbsp;Satyamitra L. Shekh ,&nbsp;Anitaba Chauhan ,&nbsp;Kopal Kapoor ,&nbsp;Aneri Joshi ,&nbsp;Devanshi Gajjar ,&nbsp;Sriram Seshadri ,&nbsp;Dhwani Jhala ,&nbsp;Chaitanya G. Joshi ,&nbsp;Amrutlal Patel","doi":"10.1016/j.vaccine.2026.128331","DOIUrl":"10.1016/j.vaccine.2026.128331","url":null,"abstract":"<div><div>Leptospirosis is the most widespread and under-recognized zoonotic disease with around 1.03 million cases and ∼ 60,000 reported fatalities occurring each year. It is a threat to humans as well as animals and can only be avoided by appropriate immunization. In this study, epitopes from proteins present on the exterior membrane of selected pathogenic <em>Leptospira</em> species were used as immunogens <em>viz.</em> OMPL1, LipL32, LipL41 and LipL46. Conserved epitopes from each of the proteins across 8 species of <em>Leptospira</em> were screened and used to generate a multi-epitope vaccine that activates B cells, CD4+ and CD8+ cells. Six vaccine constructs were analyzed employing various immunoinformatics tools for physicochemical properties, structure prediction followed by validation, docking with immune receptors and molecular dynamics simulation. The vaccine construct 4 (LH) was found to comply with all the desired parameters to further consider for <em>in vivo</em> efficacy evaluation. For <em>in vivo</em> validation, gene for LH was cloned in a pVAX1 vector to be used as a DNA vaccine and in pET30a vector to express protein vaccine. DNA and protein vaccines were administered intramuscularly in ICR male mice along with adjuvant alhydrogel. Both types of vaccines elicited strong immune response evidenced from significantly increased serum IgG level evaluated by ELISA post the duration of 14 to 42 days. IFN-γ cytokine producing T cells were significantly stimulated in protein vaccine as revealed by flow cytometry suggesting the priming of CD4+ and CD8+ T cells by vaccine. The neutralizing antibody response to <em>Leptospira</em> serovars was confirmed with microscopic agglutination test. In summary, this study illustrates the prospective of multi-epitope DNA and protein vaccines incorporating epitopes from four outer membrane proteins to generate a strong immune response, paving the way forward for protection during challenge study against virulent <em>Leptospira</em> pathogens in animal model.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128331"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146168617","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":"Association of parental vaccination readiness and descriptive norms with childhood vaccination status","authors":"Wakana Maki ,&nbsp;Kazue Ishitsuka ,&nbsp;Naho Morisaki ,&nbsp;Masaki Machida ,&nbsp;Takahiro Tabuchi","doi":"10.1016/j.vaccine.2026.128337","DOIUrl":"10.1016/j.vaccine.2026.128337","url":null,"abstract":"<div><h3>Background</h3><div>Maintaining high vaccination coverage requires understanding parental psychological factors, such as readiness conceptualized by the 7C model and descriptive norms, that shape decisions about childhood vaccinations. This study aimed to validate the Japanese short version of the Children-7C (C7C) scale, and examine how parental readiness and descriptive norms relate to vaccination status.</div></div><div><h3>Methods</h3><div>This cross-sectional study analyzed data from 5148 parents in a self-reported online survey. Structural validity and internal consistency were assessed using confirmatory factor analysis and McDonald's omega. Criterion validity was examined using structural equation modeling (SEM) for composite vaccination uptake and acceptance defined as the proportion of age-eligible vaccines received, and received or intended, respectively. Vaccine-specific SEMs were also conducted for all vaccines in the Japanese National Immunization Program—<em>Haemophilus influenzae</em> type b, pneumococcal conjugate vaccine, diphtheria–pertussis–tetanus, hepatitis B, rotavirus, measles–rubella, varicella, Japanese encephalitis, human papillomavirus, and diphtheria–tetanus, as well as mumps, influenza and COVID-19.</div></div><div><h3>Results</h3><div>The scale demonstrated acceptable structural validity (CFI = 0.97, TLI = 0.96, RMSEA = 0.092, SRMR = 0.028) and internal consistency (ω = 0.88). Factor loadings ranged from −0.51 for calculation to 0.89 for complacency. Collective responsibility, constraints, confidence, and complacency showed strong loadings, whereas compliance (λ = 0.25) and conspiracy (λ = 0.06) showed minimal loadings. Regarding criterion validity, parental readiness was positively associated with both composite uptake and acceptance. Readiness showed similar associations across routine infant vaccines, a strong association for HPV, and a weaker association for COVID-19 and seasonal influenza vaccines. Descriptive norms had a lesser overall loading but were consistently positive.</div></div><div><h3>Conclusion</h3><div>The Japanese short version of the C7C scale is valid for measuring parental vaccination readiness. Readiness consistently predicted children's vaccination status, underscoring the need to enhance readiness while also considering vaccine- and age-specific strategies.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128337"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146174751","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":"Immunogenicity and safety of two doses of the four-component recombinant meningococcal B (4CMenB) vaccine in adults with immunodeficiency","authors":"L. Sticchi ,&nbsp;A. Di Biagio ,&nbsp;A. Domnich ,&nbsp;M. Inglese ,&nbsp;M. Mikulska ,&nbsp;J. Louth ,&nbsp;R. Borrow ,&nbsp;C. Di Grazia ,&nbsp;C. Lapucci ,&nbsp;M. Bassetti ,&nbsp;G. Icardi","doi":"10.1016/j.vaccine.2026.128295","DOIUrl":"10.1016/j.vaccine.2026.128295","url":null,"abstract":"<div><h3>Background</h3><div>Individuals with immunodeficiency are at a higher risk of invasive meningococcal disease, but only a few studies have investigated the immunogenicity and safety of four-component recombinant meningococcal B (4CMenB) in this population.</div></div><div><h3>Methods</h3><div>This was a prospective, open-label, single-arm, single-center study with the aim to assess immunogenicity, reactogenicity and safety of two doses of 4CMenB in adults with acquired immunodeficiency: haematopoietic cell transplantation recipients, people living with HIV and patients candidates for/in treatment with biological drugs, such as monoclonal anti-CD20 antibodies. The primary objective was to evaluate the immunogenicity with the following endpoints: (i) geometric mean fold rise (GMFR) defined as a ratio of post-dose 2 geometric mean titres (GMTs) to baseline pre-dose 1 GMTs; (ii) proportion of subjects with 4-fold or greater increase in human complement serum bactericidal antibody assay (hSBA) from baseline to post-dose 2 and (iii) proportion of subjects with post-dose 2 hSBA titres ≥1:4. The secondary objective was to assess the reactogenicity, tolerability and safety. The trial was registered with clinicaltrials.gov (NCT04295733).</div></div><div><h3>Results</h3><div>A total of 65 patients were collected both blood samples and returned ≥1 safety diary. There was a significant (<em>P</em> &lt; 0.001) increase in GMTs independently of the study group and antigen with the corresponding GMFR ranging from 11.9 to 105. The proportion of subjects with hSBA titres ≥1:4 increased significantly and 89.2–98.5% of subjects were deemed seroprotected. Seroconversion rates were similarly high: 78.5–87.7%. The injection-site pain was the most common adverse event (AE). No serious AEs were reported.</div></div><div><h3>Conclusions</h3><div>4CMenB was immunogenic and well-tolerated in adults with immunodeficiency.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128295"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146174753","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":"A point-mutated Ag85B antigen improves recombinant bacterial expression and protects mice from aerosol M. tuberculosis challenge","authors":"Wen-Ling Hsu ,&nbsp;Yang Jiao ,&nbsp;Matthew Hvasta ,&nbsp;Kristina N. Tran ,&nbsp;Brennen T. Troyer ,&nbsp;Wei-Chiao Huang ,&nbsp;Brian Kuhlman ,&nbsp;Andres Obregon-Henao ,&nbsp;Jonathan F. Lovell","doi":"10.1016/j.vaccine.2026.128281","DOIUrl":"10.1016/j.vaccine.2026.128281","url":null,"abstract":"<div><div>Tuberculosis (TB) remains a global health problem, providing motivation for improved vaccine approaches, such as subunit vaccines targeting specific <em>Mycobacterium tuberculosis</em> (<em>M. tuberculosis</em>) antigens. Ag85B is a protein involved in cell wall biosynthesis, is abundant in <em>M. tuberculosis</em> culture supernatants, and has been incorporated in several TB vaccines candidates. We observed low expression yields of Ag85B when expressed recombinantly in <em>E. coli</em> using a histidine-tag purification approach. To address this, we utilized the ThermoMPNN protein structure algorithm to predict several stabilizing mutations in Ag85B. Of these, a single mutation, D52W, significantly enhanced expression yield in <em>E. coli</em> with good storage stability. Ag85B-52W exhibited rapid binding to liposomes incorporating cobalt-porphyrin via his-tag interaction, resulting in suppression in reactivity with an anti-his-tag antibody (due to anchoring of the his-tag in the bilayer), while the surface-displayed protein remained reactive towards anti-Ag85B antibodies. Immunization with Ag85B-52W in a liposomal vaccine elicited antigen-specific antibody and T cell responses, resulting in reduced lung bacterial burden in mice following aerosol <em>M. tuberculosis</em> challenge.</div></div><div><h3>Significance statement</h3><div>A point mutation in the <em>M. tuberculosis</em> Ag85B protein, predicted by ThermoMPNN algorithm, enhanced its antigen expression yield in <em>E. coli</em> with good storage stability. Immunization with the Ag85B mutant with a liposome vaccine system in mice resulted in antigen-specific humoral and cellular response that protected mice against <em>M. tuberculosis</em> infection. This approach could facilitate the use of recombinant Ag85B in TB vaccine development.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"76 ","pages":"Article 128281"},"PeriodicalIF":4.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098569","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}