Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

Abstract

BACKGROUND:

The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.

METHODOLOGY/PRINCIPAL FINDINGS:

A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on apical membrane antigen-1 (AMA-1) from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert). Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL) or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.

CONCLUSION/SIGNIFICANCE:

The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

• Authors: Mahamadou A Thera, Ogobara K Doumbo, Drissa Coulibaly, Dapa A Diallo, Abdoulaye K Kone, Ando B Guindo, Karim Traore, Alassane Dicko, Issaka Sagara, Mahamadou S Sissoko, Mounirou Baby, Mady Sissoko, Issa Diarra, Amadou Niangaly, Amagana Dolo, Modibo Daou, Sory I Diawara, D Gray Heppner, V Ann Stewart, Evelina Angov, Elke S Bergmann-Leitner, David E Lanar, Sheetij Dutta, Lorraine Soisson, Carter L Diggs, Amanda Leach, Alex Owusu, Marie-Claude Dubois, Joe Cohen, Jason N Nixon, Aric Gregson, Shannon L Takala, Kirsten E Lyke, Christopher V Plowe
• Journal: PloS one (PLoS One) Vol. 3 Issue 1 Pg. e1465 (Jan 23 2008) ISSN: 1932-6203 [Electronic] United States
• PMID: 18213374 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antibodies, Protozoan
• Antigens, Protozoan
• Malaria Vaccines
• Membrane Proteins
• Protozoan Proteins
• apical membrane antigen I, Plasmodium

Topics

• Adult
• Antibodies, Protozoan (blood)
• Antigens, Protozoan (immunology)
• Double-Blind Method
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Malaria Vaccines (administration & dosage, adverse effects)
• Malaria, Falciparum (prevention & control)
• Male
• Mali
• Membrane Proteins (immunology)
• Protozoan Proteins (immunology)