Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies.
Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost.
Jiang
George
G
Naval Medical Research Center, Malaria Program, Silver Spring, MD, USA.
Shi
Meng
M
Conteh
Solomon
S
Richie
Nancy
N
Banania
Glenna
G
Geneshan
Harini
H
Valencia
Anais
A
Singh
Priti
P
Aguiar
Joao
J
Limbach
Keith
K
Kamrud
Kurt I
KI
Rayner
Jonathan
J
Smith
Jonathan
J
Bruder
Joseph T
JT
King
C Richter
CR
Tsuboi
Takafumi
T
Takeo
Satoru
S
Endo
Yaeta
Y
Doolan
Denise L
DL
Richie
Thomas L
TL
Weiss
Walter R
WR
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D005822:Genetic Vectors; D008253:Macaca mulatta / Q000276:immunology*; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control / Q000662:veterinary*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016790:Plasmodium knowlesi / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014780:Viruses / Q000235:genetics
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines