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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
S. Pichyangkul,1*
U. Kum-Arb,1
K. Yongvanitchit,1
A. Limsalakpetch,1
M. Gettayacamin,2
D. E. Lanar,3
L. A. Ware,3
V. A. Stewart,3
D. G. Heppner,3
P. Mettens,4
J. D. Cohen,4
W. R. Ballou,4 and
M. M. Fukuda1
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.
* Corresponding author. Mailing address: Department of Immunology and Medicine, USAMC-AFRIMS, 315/6 Rajvithi Rd., Bangkok 10400, Thailand. Phone: (662) 644-4820. Fax: (662) 644-4784. E-mail: Sathitp{at}afrims.org
Published ahead of print on 22 October 2007.
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.
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