# A Chemical Vaccine for Malaria

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $476,454

## Abstract

Chemical vaccines for malaria, long-acting causal prophylactic drugs given by injection, are recognized as
a promising new approach for longterm protection against infection. Such therapy would benefit
populations at risk, not just those living in endemic areas but also the tens of millions of nonimmune
travellers who visit these areas every year. International malaria control efforts, though highly successful
appear to have slowed, and the availability of a chemical vaccine would provide a new tool to reduce
seasonal transmission and sustain already-accomplished malaria control. Broad-spectrum antiprotozoal
atovaquone is used at high dose to prophylax and treat immunocompromised patients for Pneumocystis
jirovecii pneumonia or toxoplasmosis; atovaquone, at substantially lower dose and in fixed combination
with proguanil is also used for causal prophylaxis and treatment of malaria. In some 20 years of use,
atovaquone alone and atovaquone+proguanil have track records of safety and efficacy in humans. We
previously established that nanoparticulate atovaquone given intramuscularly could protect mice for up to
4 weeks against a lethal sporozoite challenge. In more recent preliminary studies an alternative formulation
of atovaquone protects for at least 8 weeks, the longest interval tested, with no behavioral evidence of
muscle toxicity. The proposed work is designed to extend these preliminary findings, by establishing the
longest interval of protection, obtaining atovaquone levels at the time of challenge so as to complete
pharmacokinetic-pharmacodynamic analyses, and conducting a preliminary histopathological examination
of muscle at the injection site. Alone among the malaria prophylaxis drugs, atovaquone is administered in
combination with a second drug, proguanil. Unequivocally required for treatment of established
erythrocytic infection, the necessity of proguanil for causal prophylaxis of malaria has not been well-
examined. Proposed experiments in mice will evaluate the contribution of proguanil to causal protection
against challenge by atovaquone-sensitive and atovaquone-resistant sporozoites. This information will
provide a sound basis for deciding whether an atovaquone chemical vaccine must also include proguanil.
Experiments in this project will lay the foundation for a Phase 1/2a clinical trial of atovaquone with or
without proguanil, and they furnish a template for preclinical evaluation of chemical vaccine candidates in
the future.

## Key facts

- **NIH application ID:** 10020898
- **Project number:** 5R01AI148563-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Theresa A Shapiro
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $476,454
- **Award type:** 5
- **Project period:** 2019-09-19 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10020898

## Citation

> US National Institutes of Health, RePORTER application 10020898, A Chemical Vaccine for Malaria (5R01AI148563-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10020898. Licensed CC0.

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