The primary long-term objective of this proposed research is to provide basic fundamental molecular biological and immunobiological information that will aid in the development of a blood stage merozoite vaccine against Plasmodium vivax, one of the two most prevalent species of human malaria. Although the parasite under investigation is P. vivax, the results of the proposed research will also have relevance towards increasing the understanding of the biology of P. falciparum merozoites, the other major species of human malaria. The proposed investigations will continue our characterizations of several P. vivax merozoite proteins and the genes encoding them that 1) have directly or indirectly an apparent function in the receptor mediated processes of merozoite invasion of erythrocytes, and 2) are likely to have a role in affecting the immunobiological relationship between P. vivax and humans by stimulating anti-P. vivax immune responses. Specifically, the proteins under study are organized internally or externally at the invasive apical pole of the merozoite or comprise elements of the organized surface coat of merozoites. Three of these proteins bind to erythrocytes in a manner consistent with receptor-like specificity and parasite biology and, therefore, likely have a direct role in the initial molecular events of merozoite invasion. The structure and binding domains of these proteins will be determined through immunochemical, molecular biological, and recombinant expression technologies in order to more effectively assess biological function and immunogenicity. The molecular and biological characterization of a fourth apically located protein could provide further insights into the role(s) of the poorly characterized merozoite apical microneme organelles and their contents in invasion. Three other proteins are members of a newly discovered family of merozoite coat proteins that are immunogens but also may play a paradoxical role in host-parasite biology by stimulating a naturally acquired immune mechanism that limits asexual blood stage parasitemias, while, concurrently, they may also have a role in promoting chronicity. The research is aimed at investigating aspects of the genetics and diversity of the family members and how this may affect the immune response mechanisms induced by these proteins and vice versa. The coordinated use of in-vitro merozoite invasion and attachment assays, immuno-electron microscopy, defined antibody and recombinant DNA reagents that have already been or will be developed, and the ability to use the simian malaria model, P. knowlesi, in addition to P. vivax, will aid in the more precise determination and clarification of the location(s), function, structure and possible interactive relationships of the merozoite proteins under investigation and further the rational development of potential vaccine candidates.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
New York University
Schools of Medicine
New York
United States
Zip Code
Anderson, D C; Lapp, Stacey A; Barnwell, John W et al. (2017) A large scale Plasmodium vivax- Saimiri boliviensis trophozoite-schizont transition proteome. PLoS One 12:e0182561
Rodrigues-da-Silva, Rodrigo Nunes; Martins da Silva, João Hermínio; Singh, Balwan et al. (2016) In silico Identification and Validation of a Linear and Naturally Immunogenic B-Cell Epitope of the Plasmodium vivax Malaria Vaccine Candidate Merozoite Surface Protein-9. PLoS One 11:e0146951
Anderson, D C; Lapp, Stacey A; Akinyi, Sheila et al. (2015) Plasmodium vivax trophozoite-stage proteomes. J Proteomics 115:157-76
Moreno, Alberto; Cabrera-Mora, Monica; Garcia, Anapatricia et al. (2013) Plasmodium coatneyi in rhesus macaques replicates the multisystemic dysfunction of severe malaria in humans. Infect Immun 81:1889-904
Jiang, Jianlin; Barnwell, John W; Meyer, Esmeralda V S et al. (2013) Plasmodium vivax merozoite surface protein-3 (PvMSP3): expression of an 11 member multigene family in blood-stage parasites. PLoS One 8:e63888
Bitencourt, Amanda R; Vicentin, Elaine C; Jimenez, Maria C et al. (2013) Antigenicity and immunogenicity of Plasmodium vivax merozoite surface protein-3. PLoS One 8:e56061
Galinski, Mary R; Meyer, Esmeralda V S; Barnwell, John W (2013) Plasmodium vivax: modern strategies to study a persistent parasite's life cycle. Adv Parasitol 81:1-26
Akinyi, Sheila; Hanssen, Eric; Meyer, Esmeralda V S et al. (2012) A 95 kDa protein of Plasmodium vivax and P. cynomolgi visualized by three-dimensional tomography in the caveola-vesicle complexes (Schuffner's dots) of infected erythrocytes is a member of the PHIST family. Mol Microbiol 84:816-31
Lima-Junior, J C; Jiang, J; Rodrigues-da-Silva, R N et al. (2011) B cell epitope mapping and characterization of naturally acquired antibodies to the Plasmodium vivax merozoite surface protein-3? (PvMSP-3?) in malaria exposed individuals from Brazilian Amazon. Vaccine 29:1801-11
Lima-Junior, J C; Banic, D M; Tran, T M et al. (2010) Promiscuous T-cell epitopes of Plasmodium merozoite surface protein 9 (PvMSP9) induces IFN-gamma and IL-4 responses in individuals naturally exposed to malaria in the Brazilian Amazon. Vaccine 28:3185-91

Showing the most recent 10 out of 21 publications