Safety and Immunogenicity of Heterologous Prime-Boost Immunisation with Plasmodium falciparum Malaria Candidate Vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in Healthy Gambian and Kenyan Adults

Abstract

BackgroundHeterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI).MethodologyWe conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns.ResultsChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC).ConclusionsChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted.Trial RegistrationPactr.org PACTR2010020001771828 Pactr.org PACTR201008000221638 ClinicalTrials.gov NCT01373879 NCT01373879 ClinicalTrials.gov NCT01379430 NCT01379430

Regression of Human Papillomavirus Intraepithelial Lesions Is Induced by MVA E2 Therapeutic Vaccine

“…MVA is a nonreplicating derivative of the uniquely successful smallpox vaccine. Thus, its use in humans is completely safe, as proven by many clinical trials, which have been conducted with it (Kaufmann et al, 2002;Cosma et al, 2003;Cebere et al, 2006;Dorrell et al, 2007;Jaoko et al, 2008;Currier et al, 2010;Wilck et al, 2010;Cavenaugh et al, 2011;Garcia et al, 2011;Goepfert et al, 2011;Sheehy et al, 2012;Verheust et al, 2012;Gilbert, 2013;Ogwang et al, 2013). In addition, MVA is genetically stable, easy to manufacture, and very immunogenic (Cottingham and Carroll, 2013;Gilbert, 2013) because of cross-presentation of dying vaccinia virus-infected cells by dendritic cells to T cells (Iborra et al, 2012).…”

Recent Developments in Malaria Vaccinology

“…In 2013, the ChAd63-MVA ME-TRAP alone vaccine was tested in a Phase Ib dose escalation study in healthy Gambian and Kenyan adults (Kimani et al, 2014;Ogwang et al, 2013). The encouraging immunogenicity data of the Phase I/IIa studies in UK malaria-naïve volunteers was again confirmed.…”

Correlates of protection forPlasmodium falciparummalaria vaccine development: current knowledge and future research

“…In human trials of ME-TRAP and L3-SEPTL, increased production of CD56 + bright NK cells were detected following vaccination, but were not associated with a delayed time to parasitemia [113]. However, in-cell staining assays did measure increased CD4 + IFN-g-producing cells in vaccinated groups [113,114] that were significantly associated with a delayed time to parasitemia [113]. In human studies, subcutaneous immunization with irradiated sporozoites was suboptimal and failed to elicit broad protection from infection.…”