Immunogenicity and Efficacy in Aotus Monkeys of Four Recombinant Plasmodium falciparum Vaccines in Multiple Adjuvant Formulations Based on the 19-Kilodalton C Terminus of Merozoite Surface Protein 1

doi:10.1128/IAI.68.4.2215-2223.2000

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Infection and Immunity, April 2000, p. 2215-2223, Vol. 68, No. 4
0019-9567/00/$04.00+0

Immunogenicity and Efficacy in Aotus Monkeys of Four Recombinant Plasmodium falciparum Vaccines in Multiple Adjuvant Formulations Based on the 19-Kilodalton C Terminus of Merozoite Surface Protein 1

Sanjai Kumar,¹^,^* William Collins,² Andrea Egan,¹ Anjali Yadava,¹ Olivier Garraud,¹ Michael J. Blackman,³ Jose A. Guevara Patino,³ Carter Diggs,⁴ and David C. Kaslow¹

Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, Maryland 20892¹; Division of Parasitic Diseases and Scientific Resources Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333²; Division of Parasitology, National Institute for Medical Research, London NW71AA, United Kingdom³; Malaria Vaccine Development Program, U.S. Agency for International Development, Washington, D.C. 20523⁴

Received 20 October 1999/Returned for modification 6 December 1999/Accepted 12 January 2000

The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-likeregion of the major surface protein 1 (rMSP1₁₉) of Plasmodiumfalciparum was studied in Aotus monkeys. Vaccination with eachof the four rMSP1₁₉ constructs elicited high levels of antibodiesto MSP1₁₉ but only one construct, the 19-kDa fragment expressedas a secreted fusion protein from Saccharomyces cerevisiae (yP30P2MSP1₁₉),induced a high degree of protective immunity in Aotus nancymaiagainst lethal P. falciparum challenge. Protective formulationrequired Freund's adjuvant; vaccination with yP30P2MSP1₁₉ in sixother adjuvants that are suitable for human use induced lowerlevels of antibody response and no protection. These results emphasizethe need to continue the search for an adjuvant that is comparableto Freund's adjuvant in potency and is safe for use inhumans.

^* Corresponding author. Present address: Malaria Program, Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring,MD 20910-7500. E-mail: kumars{at}nmripo.nmri.nnmc.navy.mil.

Infection and Immunity, April 2000, p. 2215-2223, Vol. 68, No. 4
0019-9567/00/$04.00+0

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