# Effect of gut microbiota composition on malaria vaccine-induced immune responses

> **NIH NIH R21** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $255,000

## Abstract

ABSTRACT
Understanding heterogeneity in vaccine-induced immune responses and its impact on efficacy outcomes is
important for developing effective vaccines. Diverse host and environmental factors, such as the gut
microbiome, can impact vaccine responses. Important roles of gut microbiota in the development and function
of the local gut and gut-distal immune system are only beginning to be appreciated. Importantly, how gut
microbiota composition may shape vaccine-induced immune responses is not fully understood. Interestingly,
malaria vaccines are initially tested in US or European individuals, who have distinctly different gut microbiota
communities than individuals living throughout Africa. The effect of differential gut microbiota between US and
African individuals on immune responses to malaria vaccines may greatly impact vaccine efficacy in the target
population. The objective of this proposal is to evaluate how differential gut microbiota populations may
influence malaria vaccine-induced immune responses using a controlled, genetically tractable microbiome-
repopulated mouse model. Observations in animal models demonstrate that gut microbiota can function as
adjuvants via activation of pattern recognition receptor signaling pathways for non-adjuvanted vaccines.
Limited human observation and intervention studies (i.e., antibiotic treatment) also support the idea that gut
microbiota affect vaccine-induced immune responses. These studies highlight an urgent need to understand
better the effect of differential gut microbiota on vaccine-induced immunity. Many malaria vaccines rely on the
induction of antibody responses via germinal center (GC) reactions, including the two recently approved by
WHO (RTS,S and R21) and pre-clinical malaria vaccine candidates under investigation in the laboratory of Dr.
Srinivasan. These studies underscore the importance of robust antibody titer in mediating parasite
neutralization of sporozoites (infecting hepatocytes) and merozoites (infecting erythrocytes). Dr. Schmidt's
laboratory has shown in mice that differences in gut microbiota determine the magnitude and quality of GC
reactions and efficient control of parasites following Plasmodium yoelii (Py) infection. These observations
support the central hypothesis that gut microbiota composition, through its effects on GC reaction, will impact
the quantity and quality of malaria vaccine-induced immune responses, thereby influencing vaccine efficacy.
We will test this hypothesis through the following aims: Specific Aim 1. How do differential murine gut
microbiota populations impact malaria vaccine-induced antibody responses? Specific Aim 2. How do African
and US human gut microbiota communities shape malaria vaccine-induced antibody responses?

## Key facts

- **NIH application ID:** 10998039
- **Project number:** 1R21AI186331-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Nathan Schmidt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $255,000
- **Award type:** 1
- **Project period:** 2024-06-24 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10998039

## Citation

> US National Institutes of Health, RePORTER application 10998039, Effect of gut microbiota composition on malaria vaccine-induced immune responses (1R21AI186331-01). Retrieved via AI Analytics 2026-07-25 from https://api.ai-analytics.org/grant/nih/10998039. Licensed CC0.

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