Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142) administered intramuscularly with adjuvant system AS01

Nekoye Otsyula, Evelina Angov, Elke Bergmann-Leitner, Margaret Koech, Farhat Khan, Jason Bennett, Lucas Otieno, James Cummings, Ben Andagalu, Donna Tosh, John Waitumbi, Nancy Richie, Meng Shi, Lori Miller, Walter Otieno, Godfrey Allan Otieno, Lisa Ware, Brent House, Olivier Godeaux, Marie Claude DuboisBernhards Ogutu, W. Ripley Ballou, Lorraine Soisson, Carter Diggs, Joe Cohen, Mark Polhemus, D. Gray Heppner, Christian F. Ockenhouse*, Michele D. Spring

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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§ssub§42§esub§ 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 MSP142 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 MSP142 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, the antibody responses demonstrated to this vaccine candidate, both quantitative (total antibody titres) and qualitative (functional antibodies inhibiting parasite growth) warrant further consideration of its application in endemic settings. Trial registrations. Clinical Trials NCT00666380.

Original languageEnglish
Article number29
JournalMalaria Journal
Volume12
Issue number1
DOIs
StatePublished - 2013
Externally publishedYes

Keywords

  • Malaria
  • Merozoite surface protein-1
  • Plasmodium
  • Vaccine

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