Testing the efficacy of a recombinant merozoite surface protein (MSP-1(19) of Plasmodium vivax in Saimiri boliviensis monkeys.
Saimiri boliviensis monkeys were immunized with the yeast-expressed recombinant protein yP2P30Pv200(19). The antigen consisted of the C-terminus (amino acid Asn1622-Ser1729) of the merozoite surface protein 1 of the Plasmodium vivax Salvador I strain. Two universal T helper cell epitopes (P2 and P30) of tetanus toxin and six histidine residues for purification purposes were attached to the N- and C-termini, respectively. Four groups of five monkeys were given three immunizations at four-week intervals with either 250 microg of yP2P30Pv200(19) formulated with nonionic block copolymer P1005, 250 microg of antigen adsorbed to alum, 250 microg of antigen in phosphate-buffered saline (PBS), or PBS alone. Five weeks after the last immunization, each animal was inoculated with 100,000 parasitized erythrocytes of the Salvador I strain of P. vivax. Animals were splenectomized one week after challenge to increase parasite densities; after seven weeks of infection, animals were treated. Eighteen weeks later, the animals were rechallenged with the homologous parasite. Following the first challenge, three monkeys immunized with the antigen with P1005 were protected; no animals were protected from rechallenge. One monkey immunized with yP2P30Pv200(19) with alum was protected; no protection was seen after rechallenge. Two monkeys immunized with antigen alone were protected; none were protected from rechallenge. One control animal had a low parasite count following primary infection; none were protected against rechallenge. Adverse reactions were only observed with animals receiving P1005. It is proposed that splenectomy of the monkeys prevented adequate assessment of the efficacy of this antigen. Identification of a monkey host that supports high density parasitemia without splenectomy appears needed before further testing of blood-stage vaccines against P. vivax.
Collins
W E
WE
Division of Parasitic Diseases and Scientific Resources Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341-3724, USA.
Kaslow
D C
DC
Sullivan
J S
JS
Morris
C L
CL
Galland
G G
GG
Yang
C
C
Saekhou
A M
AM
Xiao
L
L
Lal
A A
AA
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D017780:Malaria Vaccines / Q000276:immunology / Q000592:standards*; D016780:Malaria, Vivax / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D015767:Mefloquine / Q000627:therapeutic use; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D018512:Parasitemia; D010966:Plasmodium vivax / Q000276:immunology*; D012453:Saimiri; D013156:Splenectomy; D014614:Vaccines, Synthetic / Q000276:immunology / Q000592:standards*
D000276:Adjuvants, Immunologic; D000962:Antimalarials; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D014614:Vaccines, Synthetic; D015767:Mefloquine