Pfag, a multivalent peptide vaccine against malaria

The National Institute of Allergy and Infectious Diseases awarded L2 Diagnostics LLC $599,954 on September 15, 2025, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop PFAG, a multivalent peptide vaccine against malaria.

The project, designated Phase I STTR, optimizes a prototype vaccine construct composed of short synthetic peptides representing specific immunogenic epitopes of the Plasmodium falciparum circumsporozoite (CSP) and Anopheles gambiae trio (AG trio) proteins, and conducts efficacy testing to confirm optimal construct design. The prototype has demonstrated immunogenicity to target antigens and sterile immunity in outbred heterogenous CD-1 mouse models. The long-term goal is to develop a peptide-based vaccine for use alone as a multivalent CSP/AG trio vaccine or co-administered with existing pre-erythrocytic vaccines such as RTS,S and R21 to produce more robust immunological initial or boost responses. The vaccine targets deployment in malaria-endemic, resource-poor countries, where a peptide-based approach offers favorable safety, production, and cost profiles relative to current eradication tools limited by efficacy, cost, and logistics constraints.

L2 Diagnostics LLC, a for-profit small business based in Woodbridge, Connecticut, performs the work in New Haven, Connecticut. The performance period runs through August 31, 2027.

Abstract

Pfag is our novel malaria vaccine, composed of short synthetic peptides representing specific immunogenic epitopes of the plasmodium falciparum circumsporozoite (CSP) and anopheles gambiae trio (AG trio) proteins. Our prototype PF AG has yielded outstanding early results, including immunogenicity to target antigens and to achieve sterile immunity in an outbred heterogenous CD-1 mouse model. This phase I feasibility sttr project aims to (I) optimize the prototype pfag vaccine construct and (II) conduct efficacy testing to confirm the optimal construct design. Our long-term goal is to develop a novel peptide-based vaccine that can be used alone as a multivalent CSP/agtrio vaccine or CO-administered with existing pre-erythrocytic vaccines such as RTS, S and R21 for a more robust immunological initial or boost response. Our target customers include global health and government organizations calling on developing new tools to eradicate malaria. A peptide-based vaccine's safety, production, and cost profile are favorable for addressing the real-world challenges of deploying a vaccine in malaria-endemic, resource-poor countries, where the current malaria eradication approach is limited by efficacy, cost, and logistics issues.