Immunogenicity and Efficacy inAotusMonkeys of Four RecombinantPlasmodium falciparumVaccines in Multiple Adjuvant Formulations Based on the 19-Kilodalton C Terminus of Merozoite Surface Protein 1

Abstract

The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP119) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP119 constructs elicited high levels of antibodies to MSP119 but only one construct, the 19-kDa fragment expressed as a secreted fusion protein fromSaccharomyces cerevisiae (yP30P2MSP119), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP119 in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans.

Plasmodium falciparumMerozoite Surface Protein 1 (MSP-1)-MSP-3 Chimeric Protein: Immunogenicity Determined with Human-Compatible Adjuvants and Induction of Protective Immune Response

“…Two of these adjuvants, alum and Montanide ISA720, were used previously in malaria vaccine trials for monkeys as well as humans (11,14,21,37). We found that immunization with MSP-Fu 24 induced a significant antibody response with all three adjuvant formulations.…”

Effect of GPI anchor moiety on the immunogenicity of DNA plasmids encoding the 19‐kDa C‐terminal portion of Plasmodium falciparum MSP‐1

“…P. falciparum MSP1 19 -specific invasion inhibitory activity has been shown to be associated with resistance to reinfection in Kenyans (6). Antibody-mediated protection against parasite infection challenge was produced in animal models immunized with either 42-kDa MSP-1 or MSP-1 19 (7)(8)(9)(10)(11). Several studies have shown that MSP-1, especially MSP-1 19 , is a target of protective antibodies against the blood-stage infection (12,13).…”

Fusion of Two Malaria Vaccine Candidate Antigens Enhances Product Yield, Immunogenicity, and Antibody-Mediated Inhibition of Parasite Growth In Vitro

“…This region is the target of some mAbs that have the ability to inhibit the growth of the parasite in vitro (9). In the Aotus monkey challenge model of P. falciparum, MSP1-19 has also proven to protect the animals from infection (10).…”