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Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice

The use of dengue virus (DENV) vaccines has been hindered by the complexities of antibody dependent enhancement (ADE). Current late-stage vaccine candidates utilize attenuated and chimeric DENVs that produce particles of varying maturities. Antibodies that are elicited by preferentially exposed epit...

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Autores principales: Scott, Connor A. P., Amarilla, Alberto A., Bibby, Summa, Newton, Natalee D., Hall, Roy A., Hobson-Peters, Jody, Muller, David A., Chappell, Keith J., Young, Paul R., Modhiran, Naphak, Watterson, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473161/
https://www.ncbi.nlm.nih.gov/pubmed/34578424
http://dx.doi.org/10.3390/v13091843
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author Scott, Connor A. P.
Amarilla, Alberto A.
Bibby, Summa
Newton, Natalee D.
Hall, Roy A.
Hobson-Peters, Jody
Muller, David A.
Chappell, Keith J.
Young, Paul R.
Modhiran, Naphak
Watterson, Daniel
author_facet Scott, Connor A. P.
Amarilla, Alberto A.
Bibby, Summa
Newton, Natalee D.
Hall, Roy A.
Hobson-Peters, Jody
Muller, David A.
Chappell, Keith J.
Young, Paul R.
Modhiran, Naphak
Watterson, Daniel
author_sort Scott, Connor A. P.
collection PubMed
description The use of dengue virus (DENV) vaccines has been hindered by the complexities of antibody dependent enhancement (ADE). Current late-stage vaccine candidates utilize attenuated and chimeric DENVs that produce particles of varying maturities. Antibodies that are elicited by preferentially exposed epitopes on immature virions have been linked to increased ADE. We aimed to further understand the humoral immunity promoted by DENV particles of varying maturities in an AG129 mouse model using a chimeric insect specific vaccine candidate, bDENV-2. We immunized mice with mature, partially mature, and immature bDENV-2 and found that immunization with partially mature bDENV-2 produced more robust and cross-neutralizing immune responses than immunization with immature or mature bDENV-2. Upon challenge with mouse adapted DENV-2 (D220), we observed 80% protection for mature bDENV-2 vaccinated mice and 100% for immature and partially mature vaccinated mice, suggesting that protection to homotypic challenge is not dependent on maturation. Finally, we found reduced in vitro ADE at subneutralising serum concentrations for mice immunized with mature bDENV-2. These results suggest that both immature and mature DENV particles play a role in homotypic protection; however, the increased risk of in vitro ADE from immature particles indicates potential safety benefits from mature DENV-based vaccines.
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spelling pubmed-84731612021-09-28 Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice Scott, Connor A. P. Amarilla, Alberto A. Bibby, Summa Newton, Natalee D. Hall, Roy A. Hobson-Peters, Jody Muller, David A. Chappell, Keith J. Young, Paul R. Modhiran, Naphak Watterson, Daniel Viruses Article The use of dengue virus (DENV) vaccines has been hindered by the complexities of antibody dependent enhancement (ADE). Current late-stage vaccine candidates utilize attenuated and chimeric DENVs that produce particles of varying maturities. Antibodies that are elicited by preferentially exposed epitopes on immature virions have been linked to increased ADE. We aimed to further understand the humoral immunity promoted by DENV particles of varying maturities in an AG129 mouse model using a chimeric insect specific vaccine candidate, bDENV-2. We immunized mice with mature, partially mature, and immature bDENV-2 and found that immunization with partially mature bDENV-2 produced more robust and cross-neutralizing immune responses than immunization with immature or mature bDENV-2. Upon challenge with mouse adapted DENV-2 (D220), we observed 80% protection for mature bDENV-2 vaccinated mice and 100% for immature and partially mature vaccinated mice, suggesting that protection to homotypic challenge is not dependent on maturation. Finally, we found reduced in vitro ADE at subneutralising serum concentrations for mice immunized with mature bDENV-2. These results suggest that both immature and mature DENV particles play a role in homotypic protection; however, the increased risk of in vitro ADE from immature particles indicates potential safety benefits from mature DENV-based vaccines. MDPI 2021-09-15 /pmc/articles/PMC8473161/ /pubmed/34578424 http://dx.doi.org/10.3390/v13091843 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Scott, Connor A. P.
Amarilla, Alberto A.
Bibby, Summa
Newton, Natalee D.
Hall, Roy A.
Hobson-Peters, Jody
Muller, David A.
Chappell, Keith J.
Young, Paul R.
Modhiran, Naphak
Watterson, Daniel
Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice
title Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice
title_full Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice
title_fullStr Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice
title_full_unstemmed Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice
title_short Implications of Dengue Virus Maturation on Vaccine Induced Humoral Immunity in Mice
title_sort implications of dengue virus maturation on vaccine induced humoral immunity in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473161/
https://www.ncbi.nlm.nih.gov/pubmed/34578424
http://dx.doi.org/10.3390/v13091843
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