Heightened innate immune state induced by viral vector leads to enhanced response to challenge and prolongs malaria vaccine protection

Cytomegalovirus is a promising vaccine vector; however, mechanisms promoting CD4 T cell responses to challenge, by CMV as a vector, are unknown. The ability of MCMV to prolong immunity generated by short-lived malaria vaccine was tested. MCMV provided non-specific protection to challenge with Plasmo...

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Bibliographic Details
Published in:iScience 2024-12, Vol.27 (12), p.111468, Article 111468
Main Authors: Gbedande, Komi, Ibitokou, Samad A., Endrino, Mark Joseph D., Yap, George S., Brown, Michael G., Stephens, Robin
Format: Article
Language:English
Subjects:
Biological sciences
Immune response
Immunology
Microbiology
Natural sciences
Viral microbiology
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Summary:Cytomegalovirus is a promising vaccine vector; however, mechanisms promoting CD4 T cell responses to challenge, by CMV as a vector, are unknown. The ability of MCMV to prolong immunity generated by short-lived malaria vaccine was tested. MCMV provided non-specific protection to challenge with Plasmodium and increased interleukin-12 (IL-12) and CD8α+ dendritic cell (DC) numbers through prolonged MCMV-dependent interferon gamma (IFN-γ) production. This late innate response to MCMV increased IL-12 upon challenge and increased the polyclonal CD4 effector T cell response to Plasmodium, protecting in an IL-12-dependent manner. Although Plasmodium-vaccine-induced protection decayed by d200, MCMV restored protection through IFN-γ. Mechanistically, protection depended on MCMV-induced-IFN-γ increasing CD8α+ DCs and IL-12p40. MCMV expressing a Plasmodium epitope increased parasite-specific CD4 effector and effector memory T cells persisting after malaria vaccination, both phenotypes reported to protect. Overall, enhanced innate cell status, a mechanism of heterologous protection by MCMV, led to a stronger T cell response to challenge. [Display omitted] •MCMV-B5 vector maintains specific CD4 T cells and effector memory phenotype•IFN-γ from persistent MCMV increases CD8α+ DCs, IL-12, and effector T cell response•Neutralization of IL-12 during challenge limits MCMV-based protection•MCMV-induced innate immune state improves T cell response to Plasmodium challenge Natural sciences; Biological sciences; Immunology; Immune response; Microbiology; Viral microbiology
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2024.111468