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Recombinant modified vaccinia virus Ankara-based malaria vaccines.

ABSTRACT: A safe and effective malaria vaccine is a crucial part of the roadmap to malaria elimination/eradication by the year 2050. Viral-vectored vaccines based on adenoviruses and modified vaccinia virus Ankara (MVA) expressing malaria immunogens are currently being used in heterologous prime-boost regimes in clinical trials for induction of strong antigen-specific T-cell responses and high-titer antibodies. Recombinant MVA is a safe and well-tolerated attenuated vector that has consistently shown significant boosting potential. Advances have been made in large-scale MVA manufacture as high-yield producer cell lines and high-throughput purification processes have recently been developed. This review describes the use of MVA as malaria vaccine vector in both preclinical and clinical studies in the past 5 years.

SUBMITTER: Sebastian S

PROVIDER: S-EPMC9491075 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Recombinant modified vaccinia virus Ankara-based malaria vaccines.

Sebastian Sarah S Gilbert Sarah C SC

Expert review of vaccines 20151029 1

A safe and effective malaria vaccine is a crucial part of the roadmap to malaria elimination/eradication by the year 2050. Viral-vectored vaccines based on adenoviruses and modified vaccinia virus Ankara (MVA) expressing malaria immunogens are currently being used in heterologous prime-boost regimes in clinical trials for induction of strong antigen-specific T-cell responses and high-titer antibodies. Recombinant MVA is a safe and well-tolerated attenuated vector that has consistently shown sign ...[more]

PMID: 26511884

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Project description:BackgroundAlthough the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine JYNNEOS. Given the potential threat of MPXV resurgence and need for vaccine alternatives, we aimed to assess the capacity COH04S1 and its synthetic MVA (sMVA) backbone to confer MPXV-specific immunity.MethodsWe evaluated orthopoxvirus-specific and MPXV cross-reactive immune responses in samples collected during a Phase 1 clinical trial of COH04S1 and in non-human primates (NHP) vaccinated with COH04S1 or its sMVA backbone. MPXV cross-reactive immune responses in COH04S1-vaccinated healthy adults were compared to responses measured in healthy subjects vaccinated with JYNNEOS. Additionally, we evaluated the protective efficacy of COH04S1 and sMVA against mpox in mpox-susceptible CAST/EiJ mice.ResultsCOH04S1-vaccinated individuals develop robust orthopoxvirus-specific humoral and cellular responses, including cross-reactive antibodies to MPXV-specific virion proteins as well as MPXV cross-neutralizing antibodies in 45% of the subjects. In addition, NHP vaccinated with COH04S1 or sMVA show similar MPXV cross-reactive antibody responses. Moreover, MPXV cross-reactive humoral responses elicited by COH04S1 are comparable to those measured in JYNNEOS-vaccinated subjects. Finally, we show that mice vaccinated with COH04S1 or sMVA are protected from lung infection following challenge with MPXV clade IIb.1.ConclusionsThese results demonstrate the capacity of sMVA vaccines to elicit cross-reactive and protective orthopox-specific immunity against MPXV, suggesting that COH04S1 and sMVA could be developed as bivalent or monovalent mpox vaccine alternatives against MPXV.

Dataset Information

Recombinant modified vaccinia virus Ankara-based malaria vaccines.

Publications

Recombinant modified vaccinia virus Ankara-based malaria vaccines.

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