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Infection and Immunity, January 2008, p. 229-238, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.00977-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Preclinical Evaluation of the Safety and Immunogenicity of a Vaccine Consisting of Plasmodium falciparum Liver-Stage Antigen 1 with Adjuvant AS01B Administered Alone or Concurrently with the RTS,S/AS01B Vaccine in Rhesus Primates

Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand,¹ Department of Veterinary Medicine, AFRIMS, Bangkok, Thailand,² Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, Maryland,³ GlaxoSmithKline Biologicals, Rixensart, Belgium⁴

Received 18 July 2007/ Returned for modification 11 September 2007/ Accepted 11 October 2007

Several lines of evidence suggest that targeting pre-erythrocytic-stage parasites for malaria vaccine development can provide sterile immunity. The objectives of this study were (i) to evaluate preclinically the safety and immunogenicity of a new recombinant pre-erythrocytic-stage antigen, liver-stage antigen 1 (LSA1), in nonhuman primates; and (ii) to investigate the potential for immune interference between LSA1 and the leading malaria vaccine candidate, RTS,S, by comparing the immune responses after single-antigen vaccination to responses after simultaneous administration of both antigens at separate sites. Using a rhesus monkey model, we found that LSA1 formulated with the GlaxoSmithKline proprietary adjuvant system AS01B (LSA1/AS01B) was safe and immunogenic, inducing high titers of antigen-specific antibody and CD4⁺ T-cell responses, as monitored by the production of interleukin-2 and gamma interferon, using intracellular cytokine staining. RTS,S/AS01B vaccination was well tolerated and demonstrated robust antibody and moderate CD4⁺ T-cell responses to circumsporozoite protein (CSP) and HBsAg. Positive CD8⁺ T-cell responses to HBsAg were detected, whereas the responses to CSP and LSA1 were negligible. For both LSA1/AS01B and RTS,S/AS01B, no statistically significant differences were observed between individual and concurrent administration in the magnitude or duration of antibody and T-cell responses. Our results revealed that both pre-erythrocytic-stage antigens were safe and immunogenic, administered either separately or simultaneously to rhesus monkeys, and that no significant immune cross interference occurred with concurrent separate-site administration. The comparison of the profiles of immune responses induced by separate-site and single-site vaccinations with LSA1 and RTS,S warrants further investigation.

Published ahead of print on 22 October 2007.

Editor: W. A. Petri, Jr.

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