# Suppression of anti-malarial humoral immune responses by gamaherpesviruses

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $383,241

## Abstract

The humoral response to malaria is critical in the control of blood stage parasitemia and the breadth of
the antibody response is protective against the development of clinical malaria. It is not understood why
some children fail to develop adequate humoral immune responses to Plasmodium infection early in
life. Both Plasmodium falciparum malaria and Epstein Barr virus (EBV) are childhood infections in sub-
Saharan Africa. The majority of children become seropositive for EBV within the first years of life, an
event that is normally asymptomatic but accompanied by potent immunosuppression. The long term
goal of this proposal is to provide mechanistic evidence that overlapping acute gammaherpesvirus coin-
fections are responsible for suppressing the development of humoral immunity during Plasmodium infection in children. Using well-established mouse models of EBV (MHV68) and malaria the objective of
this proposal is to identify how acute MHV68 co-infections suppress the development of anti-malaria
humoral immunity. The central hypothesis of this proposal is that the induction of IL-10 by M2 in
MHV68-infected B cells impairs the ability of T follicular helper cells to provide B cell help for effective
antibody production to incoming Plasmodium infection. This hypothesis has been formulated from our
published and preliminary data showing that M2 induces substantial amount of IL-10 in MHV68-infected
B cells and that MHV68 can only suppress humoral immune responses to both primary and challenge
Plasmodium infection when it can synthesize the M2 protein. The rationale for the proposed work is that
the development of new therapeutic strategies to ensure protective humoral immunity develops in children depends on an understanding of the contributing factors that prevent the development of the humoral response in the first place. Guided by strong preliminary data, the central hypothesis will be tested by pursuing 3 specific aims:
 Aim 1: Dissect how Tfh cells respond to an incoming Plasmodium infection in the context
 of IL-10 secretion from MHV68-infected B cells
 Aim 2: Determine whether M2 is sufficient to globally suppress anti-Plasmodium humoral
 immune responses
 Aim 3: Demonstrate that humoral immunity to P. falciparum in children is reduced during
 acute immunosuppressive EBV infection
The approach is innovative because to our knowledge we are the first to propose that impaired anti-
malarial humoral responses could be a result of a gammaherpesvirus mediated suppression. The proposed research is significant because it is expected to advance understanding of how the development of immunity to malaria can be adversely impacted by viral co-infections

## Key facts

- **NIH application ID:** 9821187
- **Project number:** 5R01AI123425-05
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Tracey Jane Lamb
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,241
- **Award type:** 5
- **Project period:** 2017-03-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9821187

## Citation

> US National Institutes of Health, RePORTER application 9821187, Suppression of anti-malarial humoral immune responses by gamaherpesviruses (5R01AI123425-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9821187. Licensed CC0.

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