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- Title
Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen.
- Authors
Bender, Nicole G.; Khare, Prachi; Martinez, Juan; Tweedell, Rebecca E.; Nyasembe, Vincent O.; López-Gutiérrez, Borja; Tripathi, Abhai; Miller, Dustin; Hamerly, Timothy; Vela, Eric M.; Davis, Ryan R.; Howard, Randall F.; Nsango, Sandrine; Cobb, Ronald R.; Harbers, Matthias; Dinglasan, Rhoel R.
- Abstract
Malaria transmission-blocking vaccines (TBVs) prevent the completion of the developmental lifecycle of malarial parasites within the mosquito vector, effectively blocking subsequent infections. The mosquito midgut protein Anopheline alanyl aminopeptidase N (AnAPN1) is the leading, mosquito-based TBV antigen. Structure-function studies identified two Class II epitopes that can induce potent transmission-blocking (T-B) antibodies, informing the design of the next-generation AnAPN1. Here, we functionally screened new immunogens and down-selected to the UF6b construct that has two glycine-linked copies of the T-B epitopes. We then established a process for manufacturing UF6b and evaluated in outbred female CD1 mice the immunogenicity of the preclinical product with the human-safe adjuvant Glucopyranosyl Lipid Adjuvant in a liposomal formulation with saponin QS21 (GLA-LSQ). UF6b:GLA-LSQ effectively immunofocused the humoral response to one of the key T-B epitopes resulting in potent T-B activity, underscoring UF6b as a prime TBV candidate to aid in malaria elimination and eradication efforts.
- Subjects
VACCINES; PLASMODIUM; MOSQUITO vectors; AMINOPEPTIDASES; EPITOPES
- Publication
NPJ Vaccines, 2021, Vol 6, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-021-00309-4