# Integrating a pre-erythrocytic component into a multistage malaria vaccine

> **NIH NIH R21** · DREXEL UNIVERSITY · 2021 · $226,750

## Abstract

Malaria control continues to attract international attention. While current integrated control efforts are
being maintained, new tools need to be added if further reduction in the global malaria burden is to be realized.
The development and introduction of an efficacious vaccine has great potential to be one such tool. However,
successes in the malaria vaccine effort to date have been limited. While there are several challenges that
must be addressed, two key issues have repeatedly emerged. First, the immunogenicity of subunit vaccines
must be improved. Second, there is no indication that immunity to these complex, multi-stage plasmodial
parasites is directed toward a single protective antigen. Vaccine candidate antigens will need to be formulated
in combination, without any reduction in the immunogenicity of individual components. Our prior efforts have
focused on both blood-stage and sexual stage vaccine targets where antibody-dependent mechanisms of
immunity are essential, but where immunogenicity of neutralizing B cell epitopes has not been optimal. In our
approach, we engineered a well-conserved, highly immunogenic, P. falciparum specific carrier protein based
on merozoite surface protein 8 that facilitates vaccine production and induces potent CD4+ T cell help for the
production of neutralizing antibodies. We demonstrated its utility as a carrier for P. falciparum blood-stage
vaccine candidates including merozoite surface protein 1, merozoite surface protein 2, reticulocyte-binding
protein homologue 5 and the 25 kDa sexual stage antigen. Of importance, neutralizing antibody responses to
targeted domains were maintained within the context of a multi-antigen, multi-stage formulation. A pre-
erythrocytic stage vaccine component is currently lacking from our formulation. In this project, we will test the
hypothesis that PfMSP8 is an effective carrier protein for a recombinant P. falciparum circumsporozoite surface
protein-based vaccine to elicit potent, durable antibody responses to multiple protective B cell epitopes (repeat
and non-repeat domains) that neutralize sporozoites. In aim 1, we will express and purify four recombinant
PfCSP-based vaccines designed to increase the breadth of immune responses to relevant epitopes, some of
which are lacking in the current PfCSP-based RTS,S vaccine. In aim 2, we will determine the magnitude and
epitope specificity of T and B cell responses elicited by each rPfCSP-based vaccine formulated with GLA-SE
as adjuvant. Following down-selection, we will evaluate the functionality and durability of vaccine-induced,
PfCSP-specific IgG in a rodent challenge model with transgenic Plasmodium berghei parasite expressing P.
falciparum CSP. Success in this effort will provide the foundation for subsequent preclinical testing in non-
human primates to determine if a rPfCSP* vaccine can be formulated in combination with existing rPfMSP1/8,
rPfMSP2/8, rPfRh5/8 and rPfs25/8 vaccines without compromising responses to indiv...

## Key facts

- **NIH application ID:** 10126495
- **Project number:** 1R21AI151765-01A1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** James Matthew Burns
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $226,750
- **Award type:** 1
- **Project period:** 2020-11-12 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10126495

## Citation

> US National Institutes of Health, RePORTER application 10126495, Integrating a pre-erythrocytic component into a multistage malaria vaccine (1R21AI151765-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10126495. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*