Affiliation:
1. Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health,1 and
2. Novavax, Inc.,2 Rockville, Maryland, and
3. Department of Tropical Medicine and Medical Microbiology, University of Hawaii, Honolulu, Hawaii3
Abstract
ABSTRACT
In an attempt to produce a more defined, clinical-grade version of a vaccine based on
Plasmodium falciparum
merozoite surface protein 1 (MSP1), we evaluated the efficacy of two recombinant forms of MSP1 in an
Aotus nancymai
challenge model system. One recombinant vaccine, bvMSP1
42
, based on the 42-kDa C-terminal portion of MSP1, was expressed as a secreted protein in baculovirus-infected insect cells. A highly pure baculovirus product could be reproducibly expressed and purified at yields in excess of 8 mg of pure protein per liter of culture. This protein, when tested for efficacy in the
Aotus
challenge model, gave significant protection, with only one of seven monkeys requiring treatment for uncontrolled parasitemia after challenge with
P. falciparum
. The second recombinant protein, P30P2MSP1
19
, has been used in previous studies and is based on the smaller, C-terminal 19-kDa portion of MSP1 expressed in
Saccharomyces cerevisiae
. Substantial changes were made in its production process to optimize expression. The optimum form of this vaccine antigen (as judged by in vitro and in vivo indicators) was then evaluated, along with bvMSP1
42
, for efficacy in the
A. nancymai
system. The new formulation of P30P3MSP1
19
performed significantly worse than bvMSP1
42
and appeared to be less efficacious than we have found in the past, with four of seven monkeys in the vaccinated group requiring treatment for uncontrolled parasitemia. With both antigens, protection was seen only when high antibody levels were obtained by formulation of the vaccines in Freund's adjuvant. Vaccine formulation in an alternate adjuvant, MF59, resulted in significantly lower antibody titers and no protection.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
116 articles.
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