Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP1 42 ) administered intramuscularly with adjuvant system AS01

• Published in: Malaria Journal
• Main Authors: Otsyula Nekoye, Angov Evelina, Bergmann-Leitner Elke, Koech Margaret, Khan Farhat, Bennett Jason, Otieno Lucas, Cummings James, Andagalu Ben, Tosh Donna, Waitumbi John, Richie Nancy, Shi Meng, Miller Lori, Otieno Walter, Otieno Godfrey Allan, Ware Lisa, House Brent, Godeaux Olivier, Dubois Marie-Claude, Ogutu Bernhards, Ballou W Ripley, Soisson Lorraine, Diggs Carter, Cohen Joe, Polhemus Mark, Heppner D Gray, Ockenhouse Christian F, Spring Michele D
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2013
• Subjects: Malaria; Vaccine; Merozoite surface protein-1; Plasmodium; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-12-29; https://doaj.org/article/6ee036a387234e1aa41bb45efe455f9b

Abstract Background The development of an asexual blood stage vaccine against Plasmodium falciparum malaria based on the major merozoite surface protein-1 (MSP1) antigen is founded on the protective efficacy observed in preclinical studies and induction of invasion and growth inhibitory antibody responses. The 42 kDa C-terminus of MSP1 has been developed as the recombinant protein vaccine antigen, and the 3D7 allotype, formulated with the Adjuvant System AS02A, has been evaluated extensively in human clinical trials. In preclinical rabbit studies, the FVO allele of MSP1 42 has been shown to have improved immunogenicity over the 3D7 allele, in terms of antibody titres as well as growth inhibitory activity of antibodies against both the heterologous 3D7 and homologous FVO parasites. Methods Two Phase 1 clinical studies were conducted to examine the safety, reactogenicity and immunogenicity of the FVO allele of MSP1 42 in the adjuvant system AS01 administered intramuscularly at 0-, 1-, and 2-months: one in the USA and, after evaluation of safety data results, one in Western Kenya. The US study was an open-label, dose escalation study of 10 and 50 μg doses of MSP1 42 in 26 adults, while the Kenya study, evaluating 30 volunteers, was a double-blind, randomized study of only the 50 μg dose with a rabies vaccine comparator. Results In these studies it was demonstrated that this vaccine formulation has an acceptable safety profile and is immunogenic in malaria-naïve and malaria-experienced populations. High titres of anti-MSP1 antibodies were induced in both study populations, although there was a limited number of volunteers whose serum demonstrated significant inhibition of blood-stage parasites as measured by growth inhibition assay. In the US volunteers, the antibodies generated exhibited better cross-reactivity to heterologous MSP1 alleles than a MSP1-based vaccine (3D7 allele) previously tested at both study sites. Conclusions Given that the primary effector mechanism for blood stage vaccine targets is humoral, ...