# Combination Vaccines to Interrupt Malaria Transmission

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2020 · $542,919

## Abstract

Abstract
Malaria vaccine development has focused on antigens expressed during various stages of the life cycle
of the parasite. Malaria transmission depends upon the development of intraerythrocytic sexual stages,
ingestion by female anopheline mosquitoes and subsequent sexual development in mosquitoes leading
to formation of sporozoites. An infected Anopheles mosquito initiates malaria infection cycle by injecting
sporozoites which invade hepatocytes. Hence immune interventions aimed at blocking development of
both the liver stage (pre-erythrocytic phase - PE) and sexual stage are expected to provide more
effective strategy to protect against malaria. A transmission blocking vaccine (TBV) approach targeting
antigens in the sexual stages (i.e. male and female gametocytes and gametes) and the mosquito stages
of the parasite (i.e. zygote and ookinete) is believed to be of central importance in malaria elimination
efforts. In Plasmodium falciparum, TBV target antigens include Pfs25, Pfs48/45 and Pfs230, with known
orthologs in P. vivax. While a PE stage vaccine will prevent or reduce the development of blood stage
parasites including gametocytes in an infected person, a TBV will block sexual reproduction of the
gametocytes in the mosquito. A combination of vaccines targeting both PE and sexual/midgut stages, is
expected to provide effective ways for interruption of malaria transmission, critical for elimination goal.
Using knowledge gained from our published studies on Pfs25, Pvs28 and Pfs48/45, it is now possible to
systematically evaluate a combination of these antigens along with PfCSP, an already well-established
PE stage vaccine antigen. We propose to rationally develop and evaluate multi-stage (PE and sexual),
multi-antigen (Pfs25, Pvs25, Pfs48/45, Pvs48/45 and PfCSP) and multi-species (P. falciparum and P.
vivax) vaccine combinations to interrupt malaria transmission, a long-term and ultimate goal of our
research. Using recombinant proteins, and DNA vaccines delivered by in vivo electroporation (EP), we
will determine the potency of vaccine combinations comprised of target antigens from PE and sexual
stages of P. falciparum (aim 1). In aim 2, we will evaluate and compare combination of vaccines targeting
transmission of the two major Plasmodium spp. (P. falciparum and P. vivax). The goal of studies in aim 3
is to determine outcome and immune potency of DNA vaccines by enhancing delivery of DNA plasmids
and uptake of antigen by antigen presenting cells in vivo. The proposed studies are expected to identify
most potent vaccine combination(s) and provide a rational approach for advancing effective
combination(s) to interrupt transmission of malaria, an important goal of malaria elimination strategies.

## Key facts

- **NIH application ID:** 9971448
- **Project number:** 5R01AI127544-05
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Nirbhay Kumar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $542,919
- **Award type:** 5
- **Project period:** 2017-08-04 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971448

## Citation

> US National Institutes of Health, RePORTER application 9971448, Combination Vaccines to Interrupt Malaria Transmission (5R01AI127544-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971448. Licensed CC0.

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