title: Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies.
abstract: 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.
authors: Naval Medical Research Center, Malaria Program, Silver Spring, MD, USA.
authors: George
authors: G
authors: Jiang
authors: Meng
authors: M
authors: Shi
authors: Solomon
authors: S
authors: Conteh
authors: Nancy
authors: N
authors: Richie
authors: Glenna
authors: G
authors: Banania
authors: Harini
authors: H
authors: Geneshan
authors: Anais
authors: A
authors: Valencia
authors: Priti
authors: P
authors: Singh
authors: Joao
authors: J
authors: Aguiar
authors: Keith
authors: K
authors: Limbach
authors: Kurt I
authors: KI
authors: Kamrud
authors: Jonathan
authors: J
authors: Rayner
authors: Jonathan
authors: J
authors: Smith
authors: Joseph T
authors: JT
authors: Bruder
authors: C Richter
authors: CR
authors: King
authors: Takafumi
authors: T
authors: Tsuboi
authors: Satoru
authors: S
authors: Takeo
authors: Yaeta
authors: Y
authors: Endo
authors: Denise L
authors: DL
authors: Doolan
authors: Thomas L
authors: TL
authors: Richie
authors: Walter R
authors: WR
authors: Weiss
mesh_terms: 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
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines