# Modulation of the B cell response to dengue virus infection by Plasmodium falciparum co-infection

> **NIH NIH K23** · STANFORD UNIVERSITY · 2022 · $185,273

## Abstract

Project Abstract.
 The primary goal of this Career Development Award is the successful transition of the PI from being a
mentored to an independent research scientist, studying the immunobiology of diseases of poverty affecting
children, such as dengue fever and malaria. The PI and mentoring team have designed a training plan
consisting of specific objectives that will provide the PI with practical experience conducting international
research, specialized skill using mass cytometry for immunologic research, proficiency in managing complex
data, and expertise in the development of adaptive immunity. To achieve these objectives, the team has
developed a research plan to investigate the observation that many febrile Kenyan children, with PCR-
confirmed dengue virus (DENV) viremia, did not develop serum anti-DENV IgG by 1 month after infection. This
antibody hyporesponsiveness to infection was unexpected. Due to the high transmission of Plasmodium
falciparum (Pf) malaria in the region, observations of children with simultaneous infection with both DENV and
Pf (DENV/Pf co-infection), and published evidence of impaired immunity to Pf mediated by Pf, we hypothesize
that during DENV/Pf co-infection, Pf-mediated B cell dysregulation steers antigen-stimulated
maturation of DENV-naïve B cells toward becoming atypical memory B cells, which are less responsive
to stimulation, leading to impaired development of or rapid loss of anti-DENV IgG, particularly lower
avidity antibodies. Loss of lower avidity anti-DENV antibodies may affect the risk of antibody-dependent
enhancement of DENV infection, which may affect manifestations of clinical disease. To investigate this
hypothesis, we propose two aims that will investigate two child acute febrile illness cohorts. In Aim 1, we will
investigate the clinical disease spectrum of DENV/Pf co-infected children in relation to parasitemia,
viremia, and development of anti-DENV IgG. We will use PCR to detect sub-microscopic Pf parasitemia,
which may influence clinical disease or anti-DENV antibody development. We will characterize the clinical
disease by infection and develop an acute febrile illness severity score to assess disease severity irrespective
of infectious etiology. And we will characterize, longitudinally, the post-infectious development of anti-DENV
IgG. In Aim 2, we will profile the memory B cell response after acute DENV solo- or DENV/Pf co-
infection. We will use mass cytometry to characterize changes in peripheral B cell populations over time, and
perform whole blood stimulation experiments to probe responses of peripheral B cells to antigen exposure.
Together, the data collected will answer the question of whether concurrent Pf infection impairs development of
anti-DENV antibody responses in an antigen non-specific manner. The results may raise the question of
whether and how Pf co-infection might affect vaccine-elicited serum antibody responses, which will provide
important considerations in the planning...

## Key facts

- **NIH application ID:** 10433976
- **Project number:** 5K23AI127909-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** David Manh-Tung Vu
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $185,273
- **Award type:** 5
- **Project period:** 2018-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10433976

## Citation

> US National Institutes of Health, RePORTER application 10433976, Modulation of the B cell response to dengue virus infection by Plasmodium falciparum co-infection (5K23AI127909-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10433976. Licensed CC0.

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