# Structural Vaccinology and Design of Novel Imunogens for Malaria Vaccine Development

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $722,058

## Abstract

ABSTRACT:
Malaria is a major global health problem for which a viable vaccine is desperately needed. The rationale for the
proposed research is an effective vaccine for malaria will alleviate the health and socio-economic burden
associated with the disease, especially in the face of growing antimalarial drug resistance. The central motivation
for this proposal is that design of immunogens driven by insights from the structure-function analysis of antigens
will result in a vertical leap in malaria vaccine development, and is now possible given the recent explosion in
technology for structural vaccinology and the structural definition of neutralizing epitopes in key malaria antigens.
Guided by strong preliminary data, this proposal will pursue three independent yet complementary specific aims:
1) Design pre-erythrocytic infection-blocking and transmission-blocking vaccines, 2) Develop immunogens to
focus the immune responses to neutralizing epitopes in blood-stage parasites, and 3) Combinatorially design a
multi-stage, cross-species protective immunogen. The first aim will focus on a unique multi-stage antigen that is
conserved in Plasmodium spp. and is required for infection and transmission. The second aim examines two
red-cell invasion ligands that are targets for neutralizing antibodies and required for blood-stage growth. The
third aim proposes to combine immunogen designs to elicit neutralizing responses to multiple stages of the life
cycle simultaneously. These aims will be achieved through structural vaccinology, immuno-parasitology, and
therapeutic design of novel vaccines. This proposal is innovative because our integrated and complementary
research team is well-suited to test novel concepts in vaccine design for malaria, and apply multi-disciplinary
technological innovation to comprehensively design immunogens. The proposed research is significant because
more than 200 million people every year suffer from malaria, leading to at least 500,000 deaths and an estimated
$12 billion of healthcare-related costs. Between 1,500 and 2,000 cases of malaria occur each year in the United
States alone and are reported to the CDC, with ~10% being severe and resulting in death. Prior vaccines for
malaria have failed due to antigenic variability, targeting immunodominant but non-neutralizing epitopes of
antigens, and focusing solely on a single stage of the life cycle. The proposed research is impactful because the
iterative approach will: (1) focus the immune response to existing structurally-defined neutralizing epitopes in
malaria antigens by creating epitope scaffold immunogens with flexible backbones, (2) use multiple structurally-
defined neutralizing epitopes to provide a multi-pronged protective response, (3) assess neutralization for all
stages of the malaria life cycle in established assays and mouse models, (4) utilize functional assays to guide
and validate protective immunogenicity of epitope targets, and (5) use structure-based modificatio...

## Key facts

- **NIH application ID:** 9849172
- **Project number:** 5R01AI137162-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Daniel E. Goldberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $722,058
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9849172

## Citation

> US National Institutes of Health, RePORTER application 9849172, Structural Vaccinology and Design of Novel Imunogens for Malaria Vaccine Development (5R01AI137162-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9849172. Licensed CC0.

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