Title : Immature dendritic cell targeting mRNA vaccine enhances protection from plasmodium liver stage infection by enhancing T cell responses and antibody titers against CSP repeat regions
Abstract:
In 2021, there were 247 million clinical cases and 619,000 deaths from malaria. RTS, S, the first and only WHO approved vaccine for malaria, targets the pre-erythrocytic stage antigen circumsporozoite protein (CSP) and provides only limited efficacy, reducing clinical malaria by a modest 30%. For RTS, S and other pre-erythrocytic stage targeting vaccines, the ability to produce a robust immune response, eliciting high antibody titers and engaging a productive T cell are the primary obstacles to achieving vaccine-induced protection. Here, we describe the creation of a novel CSP mRNA, chemokine fusion vaccine, designed to overcome these challenges. Vaccination with mRNA expressing full-length CSP fused to macrophage inflammatory protein 3 alpha (MIP3a), provided significantly greater protection against sporozoite challenge than vaccination with mRNA expressing full-length CSP alone. The CSP-MIP3a fusion vaccine enhanced antibody titers against highly neutralizing NANP repeat epitopes and stimulated both CD4+ and CD8+ T cell responses. Protection from sporozoite challenge correlated significantly with titers against NANP repeats and T cell stimulation, particularly CD4+ T cytokine responses.
What will audience learn from your presentation?
- Mechanisms of increasing antibody titers to vaccines
- Importance of polyfunctional T cell responses to immunogens
- Use of chemokines for dendritic cell targeting
- Benefits of fractional and delayed dosing in mRNA vaccines
- Importance of the NANP repeat region in vaccines targeting circumsporozoite protein.
