期刊
PLOS ONE
卷 7, 期 2, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0031208
关键词
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资金
- European Malaria Vaccine Development Association (EMVDA)
- European Commission [LSHP-CT-2007-037506]
- UK National Institute of Health Research through the Oxford Biomedical Research Centre [A91301]
- Wellcome Trust [084113/Z/07/Z, RTEI0, 45488/Z/05]
- PATH Malaria Vaccine Initiative
- National Institutes of Health, National Institute of Allergy and Infectious Diseases
- MRC [G0700735, G1000527] Funding Source: UKRI
- Medical Research Council [G0700735, G1000527] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0509-10233] Funding Source: researchfish
- Wellcome Trust [084113/Z/07/Z] Funding Source: Wellcome Trust
Background: Traditionally, vaccine development against the blood-stage of Plasmodium falciparum infection has focused on recombinant protein-adjuvant formulations in order to induce high-titer growth-inhibitory antibody responses. However, to date no such vaccine encoding a blood-stage antigen(s) alone has induced significant protective efficacy against erythrocytic-stage infection in a pre-specified primary endpoint of a Phase IIa/b clinical trial designed to assess vaccine efficacy. Cell-mediated responses, acting in conjunction with functional antibodies, may be necessary for immunity against blood-stage P. falciparum. The development of a vaccine that could induce both cell-mediated and humoral immune responses would enable important proof-of-concept efficacy studies to be undertaken to address this question. Methodology: We conducted a Phase Ia, non-randomized clinical trial in 16 healthy, malaria-naive adults of the chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) replication-deficient viral vectored vaccines encoding two alleles (3D7 and FVO) of the P. falciparum blood-stage malaria antigen; apical membrane antigen 1 (AMA1). ChAd63-MVA AMA1 administered in a heterologous prime-boost regime was shown to be safe and immunogenic, inducing highlevel T cell responses to both alleles 3D7 (median 2036 SFU/million PBMC) and FVO (median 1539 SFU/million PBMC), with a mixed CD4(+)/CD8(+) phenotype, as well as substantial AMA1-specific serum IgG responses (medians of 49 mu g/mL and 41 mu g/mL for 3D7 and FVO AMA1 respectively) that demonstrated growth inhibitory activity in vitro. Conclusions: ChAd63-MVA is a safe and highly immunogenic delivery platform for both alleles of the AMA1 antigen in humans which warrants further efficacy testing. ChAd63-MVA is a promising heterologous prime-boost vaccine strategy that could be applied to numerous other diseases where strong cellular and humoral immune responses are required for protection.
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