A Plasmodium vivax Plasmid DNA- and Adenovirus-Vectored Malaria Vaccine Encoding Blood-Stage Antigens AMA1 and MSP142in a Prime/Boost Heterologous Immunization Regimen Partially Protects Aotus Monkeys against Blood-Stage Challenge.
Malaria is caused by parasites of the genusPlasmodium, which are transmitted to humans by the bites ofAnophelesmosquitoes. After the elimination ofPlasmodium falciparum, it is predicted thatPlasmodium vivaxwill remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine againstP. vivaxmalaria. In this study, we assessed the immunogenicity and protective efficacy of twoP. vivaxantigens, apical membrane antigen 1 (AMA1) and the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP142) in a plasmid recombinant DNA prime/adenoviral (Ad) vector boost regimen inAotusmonkeys. Groups of 4 to 5 monkeys were immunized with plasmid DNA alone, Ad alone, prime/boost regimens with each antigen, prime/boost regimens with both antigens, and empty vector controls and then subjected to blood-stage challenge. The heterologous immunization regimen with the antigen pair was more protective than either antigen alone or both antigens delivered with a single vaccine platform, on the basis of their ability to induce the longest prepatent period and the longest time to the peak level of parasitemia, the lowest peak and mean levels of parasitemia, the smallest area under the parasitemia curve, and the highest self-cure rate. Overall, prechallenge MSP142antibody titers strongly correlated with a decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, theP. vivaxplasmid DNA/Ad serotype 5 vaccine encoding blood-stage parasite antigens AMA1 and MSP142in a heterologous prime/boost immunization regimen provided significant protection against blood-stage challenge inAotusmonkeys, indicating the suitability of these antigens and this regimen for further development.
Center for the Evaluation of Antimalarial Drugs and Vaccines, Tropical Medicine Research/Gorgas Memorial Institute of Health Studies, Panama City, Panama nobaldia@hsph.harvard.edu trichie@sanaria.com.|Department of Immunology and Infectious Diseases, Harvard University T. H. Chan School of Public Health, Boston, Massachusetts, USA.
Nicanor
N
Obaldia
Naval Medical Research Center, Silver Spring, Maryland, USA.
Michael G
MG
Stockelman
Center for the Evaluation of Antimalarial Drugs and Vaccines, Tropical Medicine Research/Gorgas Memorial Institute of Health Studies, Panama City, Panama.
William
W
Otero
Naval Medical Research Center, Silver Spring, Maryland, USA.
Jennifer A
JA
Cockrill
Naval Medical Research Center, Silver Spring, Maryland, USA.
Harini
H
Ganeshan
Naval Medical Research Center, Silver Spring, Maryland, USA.
Esteban N
EN
Abot
Vaxin Inc., Birmingham, Alabama, USA.
Jianfeng
J
Zhang
Naval Medical Research Center, Silver Spring, Maryland, USA.
Keith
K
Limbach
Naval Medical Research Center, Silver Spring, Maryland, USA.
Yupin
Y
Charoenvit
Naval Medical Research Center, Silver Spring, Maryland, USA.
Denise L
DL
Doolan
Vaxin Inc., Birmingham, Alabama, USA.
De-Chu C
DC
Tang
Naval Medical Research Center, Silver Spring, Maryland, USA nobaldia@hsph.harvard.edu trichie@sanaria.com.
Thomas L
TL
Richie
D000740:Anemia / Q000517:prevention & control; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D016645:Aotidae; D004195:Disease Models, Animal; D005260:Female; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016780:Malaria, Vivax / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D018512:Parasitemia / Q000517:prevention & control; D015800:Protozoan Proteins / Q000276:immunology*; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D008565:Membrane Proteins; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; D019444:Vaccines, DNA; C090077:apical membrane antigen I, Plasmodium
Aotus monkeys; Plasmodium vivax; adenovirus vectors; animal models; antimalarial vaccines; immunology; malaria; malaria vaccine; plasmid DNA; plasmid DNA vaccines; prime/boost immunization; recombinant adenovirus vaccines