Presenting Author: Yogesh Nepal
, Graduate research assistant at Univ. of New Mexico
Abstract:
The Plasmodium falciparum circumsporozoite protein (CSP) is an attractive malaria vaccine candidate because anti-CSP antibodies can block liver invasion and can induce sterilizing immunity against the parasite. However, current vaccines that target CSP, including RTS,S, the most advanced malaria vaccine, elicit suboptimal protective immunity that wanes over time.Thus, there is a critical need for a malaria vaccine capable of providing enhanced efficacy and durable protection in endemic areas. We have taken advantage of the recent identification of a potentially protective monoclonal antibody (mAb) that targets a uniquely vulnerable epitope (L9) within CSP. The L9 mAb can potently protect both animals and human against malaria challenge. We generated L9 VLP vaccine by displyaing L9 epitope at high valency on the surface of a Virus-Like Particles (VLPs) derived from the Qß virus. In order to increase anti-CSPantibody levels and the durability, we evaluated the immunogenicity of L9 VLPs in combination with diverse adjuvants, including TLR4, TLR9, and TLR7/8 agonists. L9 VLPs adjuvanted with Cquim, a TLR7/8 agonist, induced potent and long-lasting antibody responses. Upon malaria challenge, 80% of mice immunized with Cquim-adjuvanted L9 VLPs were protected from blood parasitemia. In contrast, only 40% of mice vaccinated with RTS,S/AS01, the only commercially available malaria vaccine, exhibited protection against blood stage parasitemia, hilighting the importance of our vaccine.
A potent pre-erthyrocytic malaria vaccine targeting a vulnerable epitope
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Poster
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Date: May 4 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1