NYVAC-Pf7: a poxvirus-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria.
The highly attenuated NYVAC vaccinia virus strain has been utilized to develop a multiantigen, multistage vaccine candidate for malaria, a disease that remains a serious global health problem and for which no highly effective vaccine exists. Genes encoding seven Plasmodium falciparum antigens derived from the sporozoite (circumsporozoite protein and sporozoite surface protein 2), liver (liver stage antigen 1), blood (merozoite surface protein 1, serine repeat antigen, and apical membrane antigen 1), and sexual (25-kDa sexual-stage antigen) stages of the parasite life cycle were inserted into a single NYVAC genome to generate NYVAC-Pf7. Each of the seven antigens was expressed in NYVAC-Pf7-infected culture cells, and the genotypic and phenotypic stability of the recombinant virus was demonstrated. When inoculated into rhesus monkeys, NYVAC-Pf7 was safe and well tolerated. Antibodies that recognize sporozoites, liver, blood, and sexual stages of P. falciparum were elicited. Specific antibody responses against four of the P.falciparum antigens (circumsporozoite protein, sporozoite surface protein 2, merozoite surface protein 1, and 25-kDa sexual-stage antigen) were characterized. The results demonstrate that NYVAC-Pf7 is an appropriate candidate vaccine for further evaluation in human clinical trials.
Tine
J A
JA
Virogenetics Corporation, Troy, New York 12180, USA.
Lanar
D E
DE
Smith
D M
DM
Wellde
B T
BT
Schultheiss
P
P
Ware
L A
LA
Kauffman
E B
EB
Wirtz
R A
RA
De Taisne
C
C
Hui
G S
GS
Chang
S P
SP
Church
P
P
Hollingdale
M R
MR
Kaslow
D C
DC
Hoffman
S
S
Guito
K P
KP
Ballou
W R
WR
Sadoff
J C
JC
Paoletti
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D017125:Genes, Protozoan; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000235:genetics*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics; D014614:Vaccines, Synthetic / Q000235:genetics*; D014616:Vaccinia virus
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D017931:DNA Primers; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic