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Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine

In 2019, the United States Food and Drug Administration accorded restricted approval to Sanofi Pasteur's Dengvaxia, a live attenuated vaccine (LAV) for dengue fever, a mosquito-borne viral disease, caused by four antigenically distinct dengue virus serotypes (DENV 1-4). The reason for this limi...

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Autores principales: Shukla, Rahul, Ramasamy, Viswanathan, Shanmugam, Rajgokul K., Ahuja, Richa, Khanna, Navin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642463/
https://www.ncbi.nlm.nih.gov/pubmed/33194810
http://dx.doi.org/10.3389/fcimb.2020.572681
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author Shukla, Rahul
Ramasamy, Viswanathan
Shanmugam, Rajgokul K.
Ahuja, Richa
Khanna, Navin
author_facet Shukla, Rahul
Ramasamy, Viswanathan
Shanmugam, Rajgokul K.
Ahuja, Richa
Khanna, Navin
author_sort Shukla, Rahul
collection PubMed
description In 2019, the United States Food and Drug Administration accorded restricted approval to Sanofi Pasteur's Dengvaxia, a live attenuated vaccine (LAV) for dengue fever, a mosquito-borne viral disease, caused by four antigenically distinct dengue virus serotypes (DENV 1-4). The reason for this limited approval is the concern that this vaccine sensitized some of the dengue-naïve recipients to severe dengue fever. Recent knowledge about the nature of the immune response elicited by DENV viruses suggests that all LAVs have inherent capacity to predominantly elicit antibodies (Abs) against the pre-membrane (prM) and fusion loop epitope (FLE) of DENV. These antibodies are generally cross-reactive among DENV serotypes carrying a higher risk of promoting Antibody-Dependent Enhancement (ADE). ADE is a phenomenon in which suboptimal neutralizing or non-neutralizing cross-reactive antibodies bind to virus and facilitate Fcγ receptor mediated enhanced entry into host cells, followed by its replication, and thus increasing the cellular viral load. On the other hand, antibody responses directed against the host-cell receptor binding domain of DENV envelope domain-III (EDIII), exhibit a higher degree of type-specificity with lower potential of ADE. The challenges associated with whole DENV-based vaccine strategies necessitate re-focusing our attention toward the designed dengue vaccine candidates, capable of inducing predominantly type-specific immune responses. If the designed vaccines elicited predominantly EDIII-directed serotype specific antibodies in the absence of prM and FLE antibodies, this could avoid the ADE phenomenon largely associated with the prM and FLE antibodies. The generation of type-specific antibodies to each of the four DENV serotypes by the designed vaccines could avoid the immune evasion mechanisms of DENVs. For the enhanced vaccine safety, all dengue vaccine candidates should be assessed for the extent of type-specific (minimal ADE) vs. cross-reactive (ADE promoting) neutralizing antibodies. The type-specific EDIII antibodies may be more directly related to protection from disease in the absence of ADE promoted by the cross-reactive antibodies.
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spelling pubmed-76424632020-11-13 Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine Shukla, Rahul Ramasamy, Viswanathan Shanmugam, Rajgokul K. Ahuja, Richa Khanna, Navin Front Cell Infect Microbiol Cellular and Infection Microbiology In 2019, the United States Food and Drug Administration accorded restricted approval to Sanofi Pasteur's Dengvaxia, a live attenuated vaccine (LAV) for dengue fever, a mosquito-borne viral disease, caused by four antigenically distinct dengue virus serotypes (DENV 1-4). The reason for this limited approval is the concern that this vaccine sensitized some of the dengue-naïve recipients to severe dengue fever. Recent knowledge about the nature of the immune response elicited by DENV viruses suggests that all LAVs have inherent capacity to predominantly elicit antibodies (Abs) against the pre-membrane (prM) and fusion loop epitope (FLE) of DENV. These antibodies are generally cross-reactive among DENV serotypes carrying a higher risk of promoting Antibody-Dependent Enhancement (ADE). ADE is a phenomenon in which suboptimal neutralizing or non-neutralizing cross-reactive antibodies bind to virus and facilitate Fcγ receptor mediated enhanced entry into host cells, followed by its replication, and thus increasing the cellular viral load. On the other hand, antibody responses directed against the host-cell receptor binding domain of DENV envelope domain-III (EDIII), exhibit a higher degree of type-specificity with lower potential of ADE. The challenges associated with whole DENV-based vaccine strategies necessitate re-focusing our attention toward the designed dengue vaccine candidates, capable of inducing predominantly type-specific immune responses. If the designed vaccines elicited predominantly EDIII-directed serotype specific antibodies in the absence of prM and FLE antibodies, this could avoid the ADE phenomenon largely associated with the prM and FLE antibodies. The generation of type-specific antibodies to each of the four DENV serotypes by the designed vaccines could avoid the immune evasion mechanisms of DENVs. For the enhanced vaccine safety, all dengue vaccine candidates should be assessed for the extent of type-specific (minimal ADE) vs. cross-reactive (ADE promoting) neutralizing antibodies. The type-specific EDIII antibodies may be more directly related to protection from disease in the absence of ADE promoted by the cross-reactive antibodies. Frontiers Media S.A. 2020-10-22 /pmc/articles/PMC7642463/ /pubmed/33194810 http://dx.doi.org/10.3389/fcimb.2020.572681 Text en Copyright © 2020 Shukla, Ramasamy, Shanmugam, Ahuja and Khanna. http://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 Cellular and Infection Microbiology
Shukla, Rahul
Ramasamy, Viswanathan
Shanmugam, Rajgokul K.
Ahuja, Richa
Khanna, Navin
Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine
title Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine
title_full Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine
title_fullStr Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine
title_full_unstemmed Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine
title_short Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine
title_sort antibody-dependent enhancement: a challenge for developing a safe dengue vaccine
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642463/
https://www.ncbi.nlm.nih.gov/pubmed/33194810
http://dx.doi.org/10.3389/fcimb.2020.572681
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