Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen

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-...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/28e79b6e90d24744bdea15515a7a039e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:28e79b6e90d24744bdea15515a7a039e
record_format	dspace
spelling	oai:doaj.org-article:28e79b6e90d24744bdea15515a7a039e2021-12-02T14:17:30ZImmunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen10.1038/s41541-021-00309-42059-0105https://doaj.org/article/28e79b6e90d24744bdea15515a7a039e2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00309-4https://doaj.org/toc/2059-0105Abstract 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.Nicole G. BenderPrachi KhareJuan MartinezRebecca E. TweedellVincent O. NyasembeBorja López-GutiérrezAbhai TripathiDustin MillerTimothy HamerlyEric M. VelaRyan R. DavisRandall F. HowardSandrine NsangoRonald R. CobbMatthias HarbersRhoel R. DinglasanNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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 Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
description	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.
format	article
author	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
author_facet	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
author_sort	Nicole G. Bender
title	Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
title_short	Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
title_full	Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
title_fullStr	Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
title_full_unstemmed	Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen
title_sort	immunofocusing humoral immunity potentiates the functional efficacy of the anapn1 malaria transmission-blocking vaccine antigen
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/28e79b6e90d24744bdea15515a7a039e
work_keys_str_mv	AT nicolegbender immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT prachikhare immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT juanmartinez immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT rebeccaetweedell immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT vincentonyasembe immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT borjalopezgutierrez immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT abhaitripathi immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT dustinmiller immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT timothyhamerly immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT ericmvela immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT ryanrdavis immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT randallfhoward immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT sandrinensango immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT ronaldrcobb immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT matthiasharbers immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen AT rhoelrdinglasan immunofocusinghumoralimmunitypotentiatesthefunctionalefficacyoftheanapn1malariatransmissionblockingvaccineantigen
_version_	1718391596716654592

Immunofocusing humoral immunity potentiates the functional efficacy of the AnAPN1 malaria transmission-blocking vaccine antigen

Ejemplares similares