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Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya

Ogutu, Bernhards R., Apollo, Odika J., McKinney, Denise, Okoth, Willis, Siangla, Joram, Dubovsky, Filip, Tucker, Kathryn, Waitumbi, John N., Diggs, Carter, Wittes, Janet, Malkin, Elissa, Leach, Amanda J., Soisson, Lorraine A., Milman, Jessica B., Otieno, Lucas, Holland, Carolyn A., Polhemus, Mark, Remich, Shon A., Ockenhouse, Christian F., MSP-1 Malaria Vaccine Working Group and et al. (2009). Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya. PLoS One,4(3):e4708-1-e4708-11.

Document type: Journal Article
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IRMA ID 75039815xPUB508
Title Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya
Author Ogutu, Bernhards R.
Apollo, Odika J.
McKinney, Denise
Okoth, Willis
Siangla, Joram
Dubovsky, Filip
Tucker, Kathryn
Waitumbi, John N.
Diggs, Carter
Wittes, Janet
Malkin, Elissa
Leach, Amanda J.
Soisson, Lorraine A.
Milman, Jessica B.
Otieno, Lucas
Holland, Carolyn A.
Polhemus, Mark
Remich, Shon A.
Ockenhouse, Christian F.
MSP-1 Malaria Vaccine Working Group
et al.
Journal Name PLoS One
Publication Date 2009
Volume Number 4
Issue Number 3
ISSN 1932-6203   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-61849177531
Start Page e4708-1
End Page e4708-11
Total Pages 11
Place of Publication United States
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DIISR)
Abstract Objective:
The antigen, falciparum malaria protein 1 (FMP1), represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1) of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System), it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccine's safety, immunogenicity, and efficacy in African children.

Methods:
A randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12–47 months in general good health.Children were randomised in a 1:1 fashion to receive either FMP1/AS02 (50 µg) or Rabipur® rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature ≥37.5°C with asexual parasitaemia of ≥50,000 parasites/µL of blood) occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE) was measured over a six-month period following third vaccinations.

Results:
374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-142 antibody concentrations increased from1.3 µg/mL to 27.3 µg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: −26% to +28%; p-value = 0.7).

Conclusions:
FMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-142 vaccine development should focus on other formulations and antigen constructs.
DOI http://dx.doi.org/10.1371/journal.pone.0004708   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)


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