Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
| Autor: | Rebecca E. Tweedell, Rhoel R. Dinglasan, Abhai K. Tripathi, Prachi Khare, Dustin Miller, Juan José Martínez, Ronald R. Cobb, Timothy Hamerly, Nicole G Bender, Borja López-Gutiérrez, Matthias Harbers, Sandrine E. Nsango, Randall F. Howard, Eric M. Vela, Ryan R. Davis, Vincent O. Nyasembe |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Protein vaccines medicine.medical_treatment Immunology Biology Article Epitope 03 medical and health sciences 0302 clinical medicine Antigen parasitic diseases medicine Pharmacology (medical) 030212 general & internal medicine RC254-282 Pharmacology Vaccines Immunogenicity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC581-607 medicine.disease QS21 Virology Malaria 030104 developmental biology Infectious Diseases Humoral immunity biology.protein Antibody Immunologic diseases. Allergy Adjuvant |
| Zdroj: | npj Vaccines, Vol 6, Iss 1, Pp 1-10 (2021) NPJ Vaccines |
| ISSN: | 2059-0105 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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