Systematic name M41021
Brief description Genes up-regulated in peripheral blood mononuclear cell immunized with ARR vs immunized by RRR in unknown (primary immunization with recombinant adenovirus 35 (Ad35)) after exposure to P. falciparum RTS,S/AS01 , time point 1D
Full description or abstract RTS,S is an advanced malaria vaccine candidate and confers significant protection against Plasmodium falciparum infection in humans. Little is known about the molecular mechanisms driving vaccine immunity. Here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with RTS,S (RRR), or in those receiving two immunizations of RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) (ARR) vector expressing circumsporozoite protein. Subsequent controlled human malaria challenge (CHMI) of the vaccinees with Plasmodium-infected mosquitoes, 3 wk after the final immunization, resulted in ~50% protection in both groups of vaccinees. Circumsporozoite protein (CSP)-specific antibody titers, prechallenge, were associated with protection in the RRR group. In contrast, ARR-induced lower antibody responses, and protection was associated with polyfunctional CD4+ T-cell responses 2 wk after priming with Ad35. Molecular signatures of B and plasma cells detected in PBMCs were highly correlated with antibody titers prechallenge and protection in the RRR cohort. In contrast, early signatures of innate immunity and dendritic cell activation were highly associated with protection in the ARR cohort. For both vaccine regimens, natural killer (NK) cell signatures negatively correlated with and predicted protection. These results suggest that protective immunity against P. falciparum can be achieved via multiple mechanisms and highlight the utility of systems approaches in defining molecular correlates of protection to vaccination.
Collection C7: Immunologic Signature
      VAX: HIPC Vaccine Response
Source publication Pubmed 28193898   Authors: Kazmin D,Nakaya HI,Lee EK,Johnson MJ,van der Most R,van den Berg RA,Ballou WR,Jongert E,Wille-Reece U,Ockenhouse C,Aderem A,Zak DE,Sadoff J,Hendriks J,Wrammert J,Ahmed R,Pulendran B
Exact source Fig S2C
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Organism Homo sapiens
Source platform HUMAN_GENE_SYMBOL
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