Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01_BWith Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP

Abstract

Background. The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector.Method. Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara–vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls.Results. No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected.Conclusions. The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types.Clinical Trials Registration. NCT01883609.

HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers

“…Strategies combining simian (chimpanzee) adenoviruses and poxvirus modified vaccinia virus Ankara (MVA) into heterologous prime-boost regimens have induced both high-titre antibody [ 41 – 46 ] and T-cell [ 47 – 50 ] responses against the shared transgene products. Here, we assessed the in vivo expression of the BG505s trimers from the viral vector-infected cells, and immunogenicity of the viral vaccines alone and with boosting by adjuvanted BG505s trimers.…”

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

“…Another promising strategy is a combination approach harnessing the ability of viral vectors to induce potent cellular immunity in combination with a protein-in-adjuvant approach to inducing high antibody titres. We have recently reported high efficacy of such an approach combining the leading malaria vaccine candidate RTS,S with ChAd63 and MVA ME-TRAP [32]. …”

Development of novel vaccine vectors: Chimpanzee adenoviral vectors

“…Both antibody responses and T-cell responses were induced in vaccinated subjects and contributed to the protection against malaria parasite infection. 44 The prime-boost vaccine regimen demonstrated a significantly reduced risk of malaria infection.…”