# Impacts of Environment, Host Genetics and Antigen Diversity on Malaria Vaccine Efficacy

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $700,429

## Abstract

ABSTRACT
Global malaria elimination has little chance of success in the absence of an effective vaccine. The leading
candidate vaccine (RTS,S) has shown only moderate efficacy in a completed Phase III trial but was recently
given scientific support by the European Medicines Agency, allowing it to be assessed for the World Health
Organization preferred medicines list as it has a potential large impact given the magnitude of malaria burden.
The vaccine does not work equally well in different populations; this variability may be due to parasite,
environmental, or host factors. Furthermore, any malaria vaccine will not be used in isolation, but rather as part
of an integrated program leveraging other control measures. Therefore, understanding the combinations of
factors which modulate the effectiveness of a malaria vaccine is essential to guide appropriate vaccine use and
formulating next-generation vaccines. This proposal is designed to improve our understanding of how RTS,S
works by evaluating key ecological, host, and parasite factors which likely impact effectiveness. The
approaches proposed will enhance our understanding of the effectiveness of RTS,S and can also be leveraged
to improve the efficacy of future malaria vaccines. Data suggest that RTS,S efficacy varies based on
transmission intensity. The first goal of this proposal is to expand these findings to a larger context. We will
investigate ecological and behavioral factors that may influence vaccine efficacy across three RTS,S trial sites
in Malawi, Ghana, and Gabon. These data, in conjunction with Phase III trial data, geographic information
system (GIS) and satellite data, and a concurrent malaria transmission intensity study, will allow us to discern
the impacts of individual and neighborhood factors on vaccine effectiveness in an “ecological” analysis of the
trial. The second goal leverages the experience in the proposed team of investigators for studying antigenic
diversity in malaria to understand the importance of strain-specific protection to the vaccine antigen
circumsporozoite protein (CS) during the trial. Recent evidence has shown strain selection by the vaccine, with
a higher level of vaccine efficacy against vaccine type CS strains. However, the longevity of strain specific
immunity is not known. If immunity to vaccine type strain is longer-lasting than to non-vaccine type strains, this
has important implications for vaccine design and suggests the need for a polyvalent vaccine. The third goal
leverages expertise in second generation sequencing and human genetics to study the impacts of host
polymorphisms associated with immune response and resistance to malaria on vaccine efficacy. The last goal
is to provide an integrative analysis of the key factors identified in the first three aims of the project to assess
their impact on vaccine efficacy in multivariate analysis. This study will be the most comprehensive evaluation
to date of factors, including host, parasite and envi...

## Key facts

- **NIH application ID:** 9906851
- **Project number:** 5R01AI137410-04
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** JEFFREY A. BAILEY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $700,429
- **Award type:** 5
- **Project period:** 2018-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906851

## Citation

> US National Institutes of Health, RePORTER application 9906851, Impacts of Environment, Host Genetics and Antigen Diversity on Malaria Vaccine Efficacy (5R01AI137410-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9906851. Licensed CC0.

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