Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
Nicole G. Bender,
Prachi Khare,
Juan Martinez,
Rebecca E. Tweedell,
Vincent O. Nyasembe,
Borja López-Gutiérrez,
Abhai Tripathi,
Dustin Miller,
Timothy Hamerly,
Eric M. Vela,
Ryan R. Davis,
Randall F. Howard,
Sandrine Nsango,
Ronald R. Cobb,
Matthias Harbers,
Rhoel R. Dinglasan
Affiliations
Nicole G. Bender
Emerging Pathogens Institute, Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida
Prachi Khare
Emerging Pathogens Institute, Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida
Juan Martinez
Ology Bioservices, Inc.
Rebecca E. Tweedell
Emerging Pathogens Institute, Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida
Vincent O. Nyasembe
Emerging Pathogens Institute, Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida
Borja López-Gutiérrez
Emerging Pathogens Institute, Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida
Abhai Tripathi
Department of Molecular Microbiology & Immunology, Johns Hopkins Malaria Research Institute
Dustin Miller
Center for Global Health, Division of Parasitic Diseases and Malaria, Malaria Research and Reference Reagent Resource Center in the Entomology Branch of the Centers for Disease Control & Prevention
Timothy Hamerly
Emerging Pathogens Institute, Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida
Eric M. Vela
Ology Bioservices, Inc.
Ryan R. Davis
Ology Bioservices, Inc.
Randall F. Howard
Infectious Disease Research Institute
Sandrine Nsango
University of Douala, Faculty of Medicine and Pharmaceutical Sciences
Ronald R. Cobb
Ology Bioservices, Inc.
Matthias Harbers
CellFree Sciences, Co. Ltd
Rhoel R. Dinglasan
Emerging Pathogens Institute, Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida
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.
