A Plasmodium vivax Plasmid DNA- and adenovirus-vectored malaria vaccine encoding blood-stage antigens AMA1 and MSP1 42 in a prime/boost heterologous immunization regimen partially protects Aotus monkeys against blood-stage challenge

Obaldia, Nicanor III, Stockelman, Michael G., Otero, William, Cockrill, Jennifer A., Ganeshan, Harini, Abot, Esteban N., Zhang, Jianfeng, Limbach, Keith, Charoenvit, Yupin, Doolan, Denise L., Tang, De-chu C., and Richie, Thomas L. (2017) A Plasmodium vivax Plasmid DNA- and adenovirus-vectored malaria vaccine encoding blood-stage antigens AMA1 and MSP1 42 in a prime/boost heterologous immunization regimen partially protects Aotus monkeys against blood-stage challenge. Clinical and Vaccine Immunology, 24 (4). pp. 1-16.

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Abstract

Malaria is caused by parasites of the genus Plasmodium, which are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of Plasmodium falciparum, it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine against P. vivax malaria. In this study, we assessed the immunogenicity and protective efficacy of two P. vivax antigens, 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 in Aotus monkeys. 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 MSP142 antibody titers strongly correlated with a decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, the P. vivax plasmid DNA/Ad serotype 5 vaccine encoding blood-stage parasite antigens AMA1 and MSP142 in a heterologous prime/boost immunization regimen provided significant protection against blood-stage challenge in Aotus monkeys, indicating the suitability of these antigens and this regimen for further development.

Item ID: 50068
Item Type: Article (Refereed Research - C1)
Keywords: Plasmodium vivax, malaria vaccine, plasmid DNA vaccines, recombinant adenovirus vaccines, prime/boost immunization, Aotus monkeys, animal models, immunology, adenovirus vectors, antimalarial vaccines, malaria, plasmid DNA
ISSN: 1556-679X
Funders: Naval Medical Research Center, U.S. Army Medical Research and Materiel Command (USAMRMC), Sistema Nacional de Investigación de Panamá (SNI), SENACYT, Panama, Harvard University
Projects and Grants: USAMRMC #DAMD-17-01- C0039
Date Deposited: 05 Sep 2017 03:57
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111716 Preventive Medicine @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 25%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 25%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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