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Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine

A successful malaria transmission blocking vaccine (TBV) requires the induction of a high antibody titer that leads to abrogation of parasite traversal of the mosquito midgut following ingestion of an infectious bloodmeal, thereby blocking the cascade of secondary human infections. Previously, we de...

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Autores principales: Howard, Gregory P., Bender, Nicole G., Khare, Prachi, López-Gutiérrez, Borja, Nyasembe, Vincent, Weiss, William J., Simecka, Jerry W., Hamerly, Timothy, Mao, Hai-Quan, Dinglasan, Rhoel R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432939/
https://www.ncbi.nlm.nih.gov/pubmed/34512663
http://dx.doi.org/10.3389/fimmu.2021.729086
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author Howard, Gregory P.
Bender, Nicole G.
Khare, Prachi
López-Gutiérrez, Borja
Nyasembe, Vincent
Weiss, William J.
Simecka, Jerry W.
Hamerly, Timothy
Mao, Hai-Quan
Dinglasan, Rhoel R.
author_facet Howard, Gregory P.
Bender, Nicole G.
Khare, Prachi
López-Gutiérrez, Borja
Nyasembe, Vincent
Weiss, William J.
Simecka, Jerry W.
Hamerly, Timothy
Mao, Hai-Quan
Dinglasan, Rhoel R.
author_sort Howard, Gregory P.
collection PubMed
description A successful malaria transmission blocking vaccine (TBV) requires the induction of a high antibody titer that leads to abrogation of parasite traversal of the mosquito midgut following ingestion of an infectious bloodmeal, thereby blocking the cascade of secondary human infections. Previously, we developed an optimized construct UF6b that elicits an antigen-specific antibody response to a neutralizing epitope of Anopheline alanyl aminopeptidase N (AnAPN1), an evolutionarily conserved pan-malaria mosquito midgut-based TBV target, as well as established a size-controlled lymph node targeting biodegradable nanoparticle delivery system that leads to efficient and durable antigen-specific antibody responses using the model antigen ovalbumin. Herein, we demonstrate that co-delivery of UF6b with the adjuvant CpG oligodeoxynucleotide immunostimulatory sequence (ODN ISS) 1018 using this biodegradable nanoparticle vaccine delivery system generates an AnAPN1-specific immune response that blocks parasite transmission in a standard membrane feeding assay. Importantly, this platform allows for antigen dose-sparing, wherein lower antigen payloads elicit higher-quality antibodies, therefore less antigen-specific IgG is needed for potent transmission-reducing activity. By targeting lymph nodes directly, the resulting immunopotentiation of AnAPN1 suggests that the de facto assumption that high antibody titers are needed for a TBV to be successful needs to be re-examined. This nanovaccine formulation is stable at -20°C storage for at least 3 months, an important consideration for vaccine transport and distribution in regions with poor healthcare infrastructure. Together, these data support further development of this nanovaccine platform for malaria TBVs.
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spelling pubmed-84329392021-09-11 Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine Howard, Gregory P. Bender, Nicole G. Khare, Prachi López-Gutiérrez, Borja Nyasembe, Vincent Weiss, William J. Simecka, Jerry W. Hamerly, Timothy Mao, Hai-Quan Dinglasan, Rhoel R. Front Immunol Immunology A successful malaria transmission blocking vaccine (TBV) requires the induction of a high antibody titer that leads to abrogation of parasite traversal of the mosquito midgut following ingestion of an infectious bloodmeal, thereby blocking the cascade of secondary human infections. Previously, we developed an optimized construct UF6b that elicits an antigen-specific antibody response to a neutralizing epitope of Anopheline alanyl aminopeptidase N (AnAPN1), an evolutionarily conserved pan-malaria mosquito midgut-based TBV target, as well as established a size-controlled lymph node targeting biodegradable nanoparticle delivery system that leads to efficient and durable antigen-specific antibody responses using the model antigen ovalbumin. Herein, we demonstrate that co-delivery of UF6b with the adjuvant CpG oligodeoxynucleotide immunostimulatory sequence (ODN ISS) 1018 using this biodegradable nanoparticle vaccine delivery system generates an AnAPN1-specific immune response that blocks parasite transmission in a standard membrane feeding assay. Importantly, this platform allows for antigen dose-sparing, wherein lower antigen payloads elicit higher-quality antibodies, therefore less antigen-specific IgG is needed for potent transmission-reducing activity. By targeting lymph nodes directly, the resulting immunopotentiation of AnAPN1 suggests that the de facto assumption that high antibody titers are needed for a TBV to be successful needs to be re-examined. This nanovaccine formulation is stable at -20°C storage for at least 3 months, an important consideration for vaccine transport and distribution in regions with poor healthcare infrastructure. Together, these data support further development of this nanovaccine platform for malaria TBVs. Frontiers Media S.A. 2021-08-27 /pmc/articles/PMC8432939/ /pubmed/34512663 http://dx.doi.org/10.3389/fimmu.2021.729086 Text en Copyright © 2021 Howard, Bender, Khare, López-Gutiérrez, Nyasembe, Weiss, Simecka, Hamerly, Mao and Dinglasan https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Howard, Gregory P.
Bender, Nicole G.
Khare, Prachi
López-Gutiérrez, Borja
Nyasembe, Vincent
Weiss, William J.
Simecka, Jerry W.
Hamerly, Timothy
Mao, Hai-Quan
Dinglasan, Rhoel R.
Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine
title Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine
title_full Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine
title_fullStr Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine
title_full_unstemmed Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine
title_short Immunopotentiation by Lymph-Node Targeting of a Malaria Transmission-Blocking Nanovaccine
title_sort immunopotentiation by lymph-node targeting of a malaria transmission-blocking nanovaccine
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432939/
https://www.ncbi.nlm.nih.gov/pubmed/34512663
http://dx.doi.org/10.3389/fimmu.2021.729086
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