TY - JOUR
T1 - Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya
AU - Ogutu, Bernhards R.
AU - Apollo, Odika J.
AU - McKinney, Denise
AU - Okoth, Willis
AU - Siangla, Joram
AU - Dubovsky, Filip
AU - Tucker, Kathryn
AU - Waitumbi, John N.
AU - Diggs, Carter
AU - Wittes, Janet
AU - Malkin, Elissa
AU - Leach, Amanda
AU - Soisson, Lorraine A.
AU - Milman, Jessica B.
AU - Otieno, Lucas
AU - Holland, Carolyn A.
AU - Polhemus, Mark
AU - Remich, Shon A.
AU - Ockenhouse, Christian F.
AU - Cohen, Joe
AU - Ballou, W. Ripley
AU - Martin, Samuel K.
AU - Angov, Evelina
AU - Stewart, V. Ann
AU - Lyon, Jeffrey A.
AU - Heppner, D. Gray
AU - Withers, Mark R.
PY - 2009
Y1 - 2009
N2 - 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 from 1.3 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.
AB - 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 from 1.3 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.
UR - http://www.scopus.com/inward/record.url?scp=61849177531&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0004708
DO - 10.1371/journal.pone.0004708
M3 - Article
C2 - 19262754
VL - 4
SP - 1
EP - 11
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 3
M1 - e4708
ER -