Abstract

With improved financial and technical supports, many malaria endemic nations are once again considering a goal of malaria elimination. However, this ambitious goal is met with tremendous technical difficulties especially in regions where Plasmodium vivax is prevalent. Interruption of malaria transmission worldwide has been recognized as one of the greatest challenges in malaria elimination. Vaccines that interrupt malaria transmission are ideally suited to this task. However, the progress in development of transmission blocking vaccines (TBVs) has been very slow. To date, we only have a few TBV immunogens with compelling evidence of transmission blocking activities. For P. vivax, TBV studies lag even behind and only two post-fertilization antigens Pvs25 and Pvs28 have been studied. Therefore, this application targets the serious deficiency of knowledge about pre-fertilization stage antigens in the neglected P. vivax parasite using systematic approaches including antigen discovery in rodent malaria parasites, validation of transmission blocking activities in P. vivax, and development of novel vaccine delivery tools.
We aim to 1) identify new sexual stage antigens and evaluate their transmission blocking potentials in the rodent malaria parasite P. berghei; 2) validate known pre-fertilization TBV candidates and newly identified candidates using fresh P. vivax clinical isolates; and 3) improve transmission blocking activities of antigens by expressing the antigens in a baculovirus surface display system and by using a TBV combination strategy targeting both pre- and post-fertilization antigens simultaneously. Results from these comprehensive studies will contribute to increased knowledge about TBV development, which is urgently needed for the ultimate elimination of vivax malaria.

Public Health Relevance

This project seeks to use the rodent malaria parasite as a model for initial screening of new transmission blocking vaccine candidates, which will be further validated in the human malaria parasite Plasmodium vivax. Identification and evaluation of transmission blocking vaccines against vivax malaria parasite are urgently needed for the impending malaria elimination campaigns.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI099611-04
Application #
8852049
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
MO, Annie X Y
Project Start
2012-06-20
Project End
2017-05-31
Budget Start
2015-06-01
Budget End
2016-05-31
Support Year
4
Fiscal Year
2015
Total Cost
Indirect Cost

  Institution

Name
China Medical University
Department
Type
DUNS #
529786253
City
Shenyang
State
Country
China
Zip Code
110122

  Publications

Liu, Qingyang; Zhao, Yan; Zheng, Li et al. (2018) The Glycosylphosphatidylinositol Transamidase Complex Subunit PbGPI16 of Plasmodium berghei Is Important for Inducing Experimental Cerebral Malaria. Infect Immun 86:
Liu, Fei; Li, Li; Zheng, Wenqi et al. (2018) Characterization of Plasmodium berghei Pbg37 as Both a Pre- and Postfertilization Antigen with Transmission-Blocking Potential. Infect Immun 86:
Zheng, Wenqi; Liu, Fei; He, Yiwen et al. (2017) Functional characterization of Plasmodium berghei PSOP25 during ookinete development and as a malaria transmission-blocking vaccine candidate. Parasit Vectors 10:8
Wang, Jian; Zheng, Wenqi; Liu, Fei et al. (2017) Characterization of Pb51 in Plasmodium berghei as a malaria vaccine candidate targeting both asexual erythrocytic proliferation and transmission. Malar J 16:458
Pang, W; Sun, X; Feng, H et al. (2016) The role of regulatory T cells during Plasmodium chabaudi chabaudi AS infection in BALB/c mice. Parasite Immunol 38:439-50
Zheng, Wenqi; Kou, Xu; Du, Yunting et al. (2016) Identification of three ookinete-specific genes and evaluation of their transmission-blocking potentials in Plasmodium berghei. Vaccine 34:2570-8
Wang, Qinghui; Zhao, Zhenjun; Zhang, Xuexing et al. (2016) Naturally Acquired Antibody Responses to Plasmodium vivax and Plasmodium falciparum Merozoite Surface Protein 1 (MSP1) C-Terminal 19 kDa Domains in an Area of Unstable Malaria Transmission in Southeast Asia. PLoS One 11:e0151900
Kou, Xu; Zheng, Wenqi; Du, Feng et al. (2016) Characterization of a Plasmodium berghei sexual stage antigen PbPH as a new candidate for malaria transmission-blocking vaccine. Parasit Vectors 9:190
Zheng, Li; Pang, Wei; Qi, Zanmei et al. (2016) Effects of transmission-blocking vaccines simultaneously targeting pre- and post-fertilization antigens in the rodent malaria parasite Plasmodium yoelii. Parasit Vectors 9:433
Zheng, Li; Pan, Yanyan; Feng, Yonghui et al. (2015) L-Arginine supplementation in mice enhances NO production in spleen cells and inhibits Plasmodium yoelii transmission in mosquitoes. Parasit Vectors 8:326

Showing the most recent 10 out of 13 publications