# Development of a pre-erythrocytic P. vivax vaccine to prevent clinical relapse

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $822,542

## Abstract

ABSTRACT
More than 3 billion people are at risk for contracting malaria caused by Plasmodium vivax (Pv). Pv infection
differs from other Plasmodium species in that it develops dormant liver stage forms called hypnozoites.
Hypnozoites can reactivate and cause blood stage malaria months to years after primary infection. It is
estimated that nearly 90% of active blood stage Pv infections are due to relapse infection and not primary
vector-mediated infection. As such, the dormant form is a major driver of Pv transmission and accounts for
nearly the entire clinical disease burden. Therefore, a vaccine that reduces or eliminates the formation of
hypnozoites, and hence reduces relapse infection, would have a significant impact on both disease burden and
transmission rates. Importantly, models suggest that this can be accomplished even in the absence of
sterilizing immunity, because hypnozoites only form in a fraction of the infected hepatocytes.
Currently there are no clinically advanced vaccines to prevent Pv infection or relapse. Development efforts
have been hampered by the inherent difficulty of working with Pv in the lab, the lack of non-CSP antigens, and
the lack of a biologically relevant model system that mimics Pv infection. Our long term goal is the
development of a pre-erythrocytic vaccine against Pv by creating novel PvCSP vaccines and P. vivax/P.
falciparum genetically attenuated parasite (GAP) vaccines that can reduce or prevent relapse infection. To this
end, we put together a research program that addresses all the major roadblocks of Pv vaccine development.
We propose to evaluate the efficacy of PvCSP vaccines against relapse, and will study novel, non-CSP
vaccine candidates that were recently identified to be part of the surface proteome. We will identify those that
can augment anti-PvCSP-mediated immunity and reduce or block the formation of hypnozoites. Finally, we will
engineer PvCSP (and potentially novel antigens) into the existing PfGAP platform that is under clinical
evaluation. Importantly, we have partnered with Mahidol University in Thailand to enable us to work with wild
type Pv sporozoites. Additionally, we propose to conduct our vaccine development in a completely humanized
model system. We will evaluate our vaccines in humanized immunoglobulin mice and test efficacy in
humanized liver mouse models of relapse infection, allowing for a more reliable translation of results in this
study toward the eventual deployment of the vaccine into the clinic. Our ultimate goal is the development of a
near clinic-ready vaccine that is effective in reducing or eliminating Pv relapse infection.

## Key facts

- **NIH application ID:** 9843652
- **Project number:** 5R01AI137234-02
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** D. Noah Sather
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $822,542
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843652

## Citation

> US National Institutes of Health, RePORTER application 9843652, Development of a pre-erythrocytic P. vivax vaccine to prevent clinical relapse (5R01AI137234-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9843652. Licensed CC0.

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