The current application is submitted in response to the notice number NOT-OD-058 entitled """"""""Enabling RPGs to Leverage NCRR Center and Centers-like Programs"""""""". The research focus of the parent grant RO1AI0470889 is to develop a vaccine targeting human malaria. Transmission blocking vaccines (TBVs) against malaria are intended to induce immunity against the stages of the parasite that infect mosquitoes so that malaria transmission is reduced or halted. The target antigens include proteins synthesized in the gametocytes (pre-fertilization antigens, in P. falciparum: Pfs230 and Pfs48/45) and in the zygotes-ookinetes (post-fertilization antigens, in P. falciparum: Pfs25 and Pfs28) and the epitopes recognized by transmission blocking antibodies are cysteine-rich reduction-sensitive conformational in nature. Studies proposed in the parent grant were aimed at (1) identifying immunologically relevant domains in the pre- fertilization antigens, (2) optimizing the combination of pre- and post-fertilization antigens by vaccine formulation in cationic lipids and vaccine delivery by in vivo electroporation, (3) evaluating a candidate DNA vaccine by in vivo electroporation in nonhuman primates (Macaca mulatta) and testing the concept that immunity against pre-fertilization antigens can be maintained by boosting during natural infection using an Aotus model for P. falciparum infection. Moreover, the development of Pfs25 transgenic P. berghei will provide an approach for in vivo evaluation of human malaria TBV based on Pfs25, as compared to a standard in vitro membrane feeding assay. Since most vaccines go through immunogenicity and functional evaluation (wherever biologically feasible) in nonhuman primates, it is now proposed to revise the scope of the parent grant to develop transgenic nonhuman malaria parasite expressing Pfs25 which would then facilitate optimization and evaluation of Pfs25-based TBV.

Public Health Relevance

Malaria causes more than 300 million infections worldwide. Our long term goal is to develop a vaccine to stop transmission of malaria. Research proposed in this application, in particular, will result in the development of a nonhuman primate model to test such human malaria transmission blocking vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
3R01AI047089-08S1
Application #
7893555
Study Section
Special Emphasis Panel (ZRG1-IMM-H (95))
Program Officer
MO, Annie X Y
Project Start
2010-09-13
Project End
2012-09-12
Budget Start
2010-09-13
Budget End
2012-09-12
Support Year
8
Fiscal Year
2010
Total Cost
$318,804
Indirect Cost
Name
Tulane University
Department
Internal Medicine/Medicine
Type
Schools of Public Health
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Datta, Dibyadyuti; Bansal, Geetha P; Gerloff, Dietlind L et al. (2017) Immunogenicity and malaria transmission reducing potency of Pfs48/45 and Pfs25 encoded by DNA vaccines administered by intramuscular electroporation. Vaccine 35:264-272
Kumar, Nirbhay (2017) Modulation of transmission success of Plasmodium falciparum gametocytes (sexual stages) in various species of Anopheles by erythrocytic asexual stage parasites. Acta Trop 176:263-269
Datta, Dibyadyuti; Bansal, Geetha P; Grasperge, Brooke et al. (2017) Comparative functional potency of DNA vaccines encoding Plasmodium falciparum transmission blocking target antigens Pfs48/45 and Pfs25 administered alone or in combination by in vivo electroporation in rhesus macaques. Vaccine 35:7049-7056
Heidari, Zahra; Arora, Jaspreet S; Datta, Dibyadyuti et al. (2017) Impact of the Charge Ratio on the In Vivo Immunogenicity of Lipoplexes. Pharm Res 34:1796-1804
Bansal, Geetha P; Weinstein, Corey S; Kumar, Nirbhay (2016) Insight into phagocytosis of mature sexual (gametocyte) stages of Plasmodium falciparum using a human monocyte cell line. Acta Trop 157:96-101
Kumar, Rajesh; Ray, Paresh C; Datta, Dibyadyuti et al. (2015) Nanovaccines for malaria using Plasmodium falciparum antigen Pfs25 attached gold nanoparticles. Vaccine 33:5064-71
Kumar, Rajesh; Ledet, Grace; Graves, Richard et al. (2015) Potent Functional Immunogenicity of Plasmodium falciparum Transmission-Blocking Antigen (Pfs25) Delivered with Nanoemulsion and Porous Polymeric Nanoparticles. Pharm Res 32:3827-36
Datta, Dibyadyuti; Bansal, Geetha P; Kumar, Rajesh et al. (2015) Evaluation of the Impact of Codon Optimization and N-Linked Glycosylation on Functional Immunogenicity of Pfs25 DNA Vaccines Delivered by In Vivo Electroporation in Preclinical Studies in Mice. Clin Vaccine Immunol 22:1013-9
Lukianova-Hleb, Ekaterina; Bezek, Sarah; Szigeti, Reka et al. (2015) Transdermal Diagnosis of Malaria Using Vapor Nanobubbles. Emerg Infect Dis 21:1122-7
Kumar, Rajesh; Angov, Evelina; Kumar, Nirbhay (2014) Potent malaria transmission-blocking antibody responses elicited by Plasmodium falciparum Pfs25 expressed in Escherichia coli after successful protein refolding. Infect Immun 82:1453-9

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