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The impact of orthopoxvirus vaccination and Mpox infection on cross-protective immunity: a multicohort observational study

2025-04-28Artigo científico Acesso aberto
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datacite.subject.fosCiências Médicas
datacite.subject.sdg03:Saúde de Qualidade
dc.contributor.authorCrandell, Jameson
dc.contributor.authorPischel, Lauren
dc.contributor.authorFang, Zhenhao
dc.contributor.authorConde, Luciana
dc.contributor.authorZhong, Yi
dc.contributor.authorLawres, Lauren
dc.contributor.authorMeira de Asis, Gustavo
dc.contributor.authorMaciel, Gabriela
dc.contributor.authorZaleski, Agnieszka
dc.contributor.authorLira, Guilherme S.
dc.contributor.authorHiga, Luiza M.
dc.contributor.authorBreban, Mallery I.
dc.contributor.authorVogels, Chantal B.F.
dc.contributor.authorCaria, João
dc.contributor.authorPinto, Ana Raquel
dc.contributor.authorAlmeida, Vasco
dc.contributor.authorMaltez, Fernando
dc.contributor.authorCordeiro, Rita
dc.contributor.authorPóvoas, Diana
dc.contributor.authorGrubaugh, Nathan D.
dc.contributor.authorAoun-Barakat, Lydia
dc.contributor.authorGrifoni, Alba
dc.contributor.authorSette, Alessandro
dc.contributor.authorCastineiras, Terezinha M.
dc.contributor.authorChen, Sidi
dc.contributor.authorYildirim, Inci
dc.contributor.authorVale, Andre M.
dc.contributor.authorOmer, Saad B.
dc.date.accessioned2026-02-06T14:30:52Z
dc.date.available2026-02-06T14:30:52Z
dc.date.issued2025-04-28
dc.description.abstractBackground: Cross-reactive immune memory responses to orthopoxviruses in humans remain poorly characterised despite their relevance for vaccine design and outbreak control. We aimed to assess the magnitude, specificity, and durability of cross-reactive immune responses elicited by smallpox vaccines and mpox virus infection. Methods: We did a multicohort observational study involving participants from the USA, Brazil, and Portugal across four groups: Dryvax (first-generation smallpox vaccine) recipients vaccinated 40-80 years ago, JYNNEOS (third-generation smallpox vaccine) recipients vaccinated within the past year, a cohort receiving both vaccines, and patients infected with clade IIb mpox. Samples were analysed for systemic and mucosal humoral responses, neutralising antibody titres, viral antigen structural analysis, and T-cell cross-reactivity to vaccina virus, cowpox virus, and mpox virus. Statistical analyses included correlation assessments and comparisons across cohorts to determine the magnitude, longevity, and breadth of immune responses. Findings: Between July 7, 2022, and Aug 3, 2023, 262 participants were recruited, resulting in analysis of 378 samples. Both first-generation and third-generation smallpox vaccines elicited vaccinia virus-reactive and mpox virus-reactive antibodies, with the strongest responses targeting the less conserved extracellular virion antigens B5 and A33. Despite high concentrations of anti-mpox virus antibodies in the plasma, cross-neutralisation activity correlated with viral antigenic distance. Higher neutralisation was observed for cowpox virus than for mpox virus, which has lower antigenic conservation with vaccina virus. Complement-mediated neutralisation enhanced mpox virus neutralisation, overcoming the limitations of antigenic distance. Dryvax recipients sustained vaccina virus neutralisation titres for over 80 years, whereas cross-reactive responses did not show this durability. JYNNEOS-induced responses waned within a year. T-cell cross-reactivity was long-lasting, detected up to 70 years after vaccination. Booster vaccinations augmented the magnitude, breadth, and longevity of cross-neutralising responses. Interpretation: Our findings highlight the potential combined role of antibody effector functions and T-cell memory in cross-protection against orthopoxviruses. Complement-mediated neutralisation enhances cross-protection, overcoming antigenic distance. These Fc-mediated functions, along with T-cell responses, contribute to effective and long-lasting immunity conferred by smallpox vaccines against other orthopoxviruses.eng
dc.description.sponsorshipThis study was supported by the Stavros Niarchos Foundation Institute for Global Infectious Disease. VSM is supported by the CAPES-YALE fellowship. Brazilian cohort set up, sample collection, and processing were supported by grants from Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/FAPERJ (reference number E−26/210.785/2021) and from Universidade Federal do Rio de Janeiro (Custo Indireto dos Projetos 24864/2022).
dc.identifier.citationLancet Microbe. 2025 Jul;6(7):101098. doi: 10.1016/j.lanmic.2025.101098. Epub 2025 Apr 28
dc.identifier.doi10.1016/j.lanmic.2025.101098
dc.identifier.eissn2666-5247
dc.identifier.pmid40311645
dc.identifier.urihttp://hdl.handle.net/10400.18/10834
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S2666524725000266?via%3Dihub
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectMpox
dc.subjectOrthopoxvirus Vaccination
dc.subjectSmallpox Vaccine
dc.subjectMulticohort Observational
dc.subjectInfecções Sistémicas e Zoonoses
dc.titleThe impact of orthopoxvirus vaccination and Mpox infection on cross-protective immunity: a multicohort observational studyeng
dc.typejournal article
dcterms.referenceshttps://ars.els-cdn.com/content/image/1-s2.0-S2666524725000266-mmc1.pdf
dspace.entity.typePublication
oaire.citation.issue7
oaire.citation.startPage101098
oaire.citation.titleThe Lancet Microbe
oaire.citation.volume6
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameCordeiro
person.givenNameRita
person.identifier.ciencia-idB518-A367-B8B7
person.identifier.orcid0000-0001-5321-3657
relation.isAuthorOfPublicationd94520e0-9d10-4302-af83-58afc79f152a
relation.isAuthorOfPublication.latestForDiscoveryd94520e0-9d10-4302-af83-58afc79f152a

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