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Sterile protection against Plasmodium knowlesi in rhesus monkeys from a malaria vaccine: comparison of heterologous prime boost strategies.
- Source :
-
PloS one [PLoS One] 2009 Aug 10; Vol. 4 (8), pp. e6559. Date of Electronic Publication: 2009 Aug 10. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Antibodies, Protozoan biosynthesis
Antigens, Protozoan genetics
Antigens, Protozoan immunology
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Genetic Vectors
Malaria parasitology
Malaria prevention & control
Malaria Vaccines administration & dosage
T-Lymphocytes immunology
Viruses genetics
Macaca mulatta immunology
Malaria veterinary
Malaria Vaccines immunology
Plasmodium knowlesi immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 4
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 19668343
- Full Text :
- https://doi.org/10.1371/journal.pone.0006559