Adenovectors induce functional antibodies capable of potent inhibition of blood stage malaria parasite growth

Bruder, Joseph T., Stefaniak, Maureen E., Patterson, Noelle B., Chen, Ping, Konovalova, Svetlana, Limbach, Keith, Campo, Joseph J., Ettyreddy, Damodar, Li, Sheng, Dubovsky, Filip, Richie, Thomas L., King, C. Richter, Long, Carole A., and Doolan, Denise (2010) Adenovectors induce functional antibodies capable of potent inhibition of blood stage malaria parasite growth. Vaccine, 28 (18). pp. 3201-3210.

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Abstract

An effective malaria vaccine remains a global health priority. Recombinant adenoviruses are a promising vaccine platform, and Plasmodium falciparum apical membrane antigen 1 (AMA1) and merozoite surface protein 1–42 (MSP1₄₂) are leading blood stage vaccine candidates. We evaluated the importance of surface antigen localization and glycosylation on the immunogenicity of adenovector delivered AMA1 and MSP1₄₂ and assessed the ability of these vaccines to induce functional antibody responses capable of inhibiting parasite growth in vitro. Adenovector delivery induced unprecedented levels of biologically active antibodies in rabbits as indicated by the parasite growth inhibition assay. These responses were as potent as published results using any other vaccine system, including recombinant protein in adjuvant. The cell surface associated and glycosylated forms of AMA1 and MSP1₄₂ elicited 99% and 60% inhibition of parasite growth, respectively. Antigens that were expressed at the cell surface and glycosylated were much better than intracellular antigens at inducing antibody responses. Good T cell responses were observed for all forms of AMA1 and MSP1₄₂. Antigen-specific antibody responses, but typically not T cell responses, were boosted by a second administration of adenovector. These data highlight the importance of rational vaccine design and support the advancement of adenovector delivery technology for a malaria vaccine.

Item ID: 42724
Item Type: Article (Refereed Research - C1)
Keywords: malaria; adenovirus vaccines; adenovector; blood stage; functional antibodies; growth inhibition assay (GIA)
ISSN: 1873-2518
Funders: PATH Malaria Vaccine Initiative (PATH-MVI), United States Army Medical Research and Material Command (USAMRMC), Pfizer Australia Senior Research Fellow (PASRF)
Date Deposited: 17 Mar 2016 04:39
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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