Impact of a Plasmodium falciparum AMA1 vaccine on antibody responses in adult malians

Alassane Dicko, David J. Diemert, Issaka Sagara, Moussa Sogoba, Mohamed B. Niambele, Mahamadoun H. Assadou, Ousmane Guindo, Beh Kamate, Mounirou Baby, Mady Sissoko, Elissa M. Malkin, Michael P. Fay, Mahamadou A. Thera, Kazutoyo Miura, Amagana Dolo, Dapa A. Diallo, Gregory Mullen, Carole A. Long, Allan Saul, Ogobara DoumboLouis H. Miller

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54 Citations (Scopus)

Abstract

Background: Apical Membrane Antigen 1 (AMA1) of Plasmodium falciparum merozoites is a leading blood-stage malaria vaccine candidate. Protection of Aotus monkeys after vaccination with AMA1 correlates with antibody responses. 

Study Design/Results: A randomized, controlled, double-blind phase 1 clinical trial was conducted in 54 healthy Malian adults living in an area of intense seasonal malaria transmission to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of yeast-expressed recombinant proteins based on sequences from the FVO and 3D7 clones of P. falciparum, adsorbed on Alhydrogel. The control vaccine was the hepatitis B vaccine (Recombivax). Participants were enrolled into 1 of 3 dose cohorts (n = 18 per cohort) and randomized 2: 1 to receive either AMA1-C1 or Recombivax. Participants in the first, second, and third cohorts randomized to receive AMA1-C1 were vaccinated with 5, 20 and 80 mg of AMA1-C1, respectively. Vaccinations were administered on days 0, 28, and 360, and participants were followed until 6 months after the final vaccination. AMA1-C1 was well tolerated; no vaccine-related severe or serious adverse events were observed. AMA1 antibody responses to the 80 mg dose increased rapidly from baseline levels by days 14 and 28 after the first vaccination and continued to increase after the second vaccination. After a peak 14 days following the second vaccination, antibody levels decreased to baseline levels one year later at the time of the third vaccination that induced little or no increase in antibody levels. 

Conclusions: Although the AMA1-C1 vaccine candidate was well-tolerated and induced antibody responses to both vaccine and non-vaccine alleles, the antibody response after a third dose given at one year was lower than the response to the initial vaccinations. Additionally, post-vaccination increases in anti-AMA1 antibody levels were not associated with significant changes in in vitro growth inhibition of P. falciparum.

Original languageEnglish
Article numbere1045
Pages (from-to)N/A
Number of pages10
JournalPL o S One
Volume2
Issue number10
DOIs
Publication statusPublished - 17 Oct 2007

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