Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults

Abstract

Protective immunity to the liver stage of the malaria parasite can be conferred by vaccine-induced T cells, but no subunit vaccination approach based on cellular immunity has shown efficacy in field studies. We randomly allocated 121 healthy adult male volunteers in Kilifi, Kenya, to Europe PMC Funders Group Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts vaccination with the recombinant viral vectors chimpanzee adenovirus 63 (ChAd63) and modified vaccinia Ankara (MVA), both encoding the malaria peptide sequence ME-TRAP (the multiple epitope string and thrombospondin-related adhesion protein), or to vaccination with rabies vaccine as a control. We gave antimalarials to clear parasitemia and conducted PCR (polymerase chain reaction) analysis on blood samples three times a week to identify infection with the malaria parasite Plasmodium falciparum. On Cox regression, vaccination reduced the risk of infection by 67% [95% confidence interval (CI), 33 to 83%; P = 0.002] during 8 weeks of monitoring. T cell responses to TRAP peptides 21 to 30 were significantly associated with protection (hazard ratio, 0.24; 95% CI, 0.08 to 0.75; P = 0.016).

Safety, Immunogenicity and Efficacy of Prime-Boost Vaccination with ChAd63 and MVA Encoding ME-TRAP against Plasmodium falciparum Infection in Adults in Senegal

“…The use of PCR detection has been found to be feasible and cost-effective in studies conducted in The Gambia and more recently in Kenya [18,19]. These clinical efficacy trials measure time to PCR-detected infection after drug clearance of parasites.…”

“…Efficacy against infection is measured over an 8-week follow-up period starting 14 days after the final vaccination (7 days after drug clearance). In a Phase IIb trial of vaccine efficacy in 120 Kenyan adults, efficacy against infection was 67% (95%CI 33% to 83%), p = 0.002, over 8 weeks of follow-up [19]. …”

Febrile illness diagnostics and the malaria-industrial complex: a socio-environmental perspective

“…As attention turns to non-communicable diseases in the Global South in recognition of these nations’ double burden of disease [104, 105], it is increasingly clear that we still have much to learn about infectious disease morbidity and mortality in SSA. And that’s to say nothing of emerging ACT resistance creeping across South Asia [106], modest results in malaria vaccine trials [107, 108], and the impact of climate change on communicable disease epidemiology [109], all of which present critical, near-term challenges that underscore the urgency of proper AFI management in SSA. Contemporary neglect of communicable disease epidemiology in SSA is perhaps best captured in comments from Wilber Downs during his Thirty-Sixth Annual Theobald Smith Memorial Lecture at the New York Society of Tropical Medicine in 1974, despite four decades of medical advances:

Whose responsibility is it to engage in such a program?

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Antigenicity of a Bacterially Expressed Triple Chimeric Antigen of Plasmodium falciparum AARP, MSP-311 and MSP-119: PfAMSP-Fu35

“…Heterologous prime/boost vaccine strategy is another attractive approach being used in developing vaccines against malaria. For example, delivery of ME-TRAP (multiepitope string- thrombospondin-related adhesion protein) by priming with ChAd63 (chimpanzee adenovirus 63) followed by a booster with modified vaccinia virus (MVA) has induced significantly high cellular responses in malaria naïve and malaria exposed individuals [14]. This prime/boost strategy is being explored for vaccine development in other disease conditions including cancer and HIV [15].…”