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A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters

Children are at risk of infection from severe acute respiratory syndrome coronavirus-2 virus (SARS-CoV-2) resulting in coronavirus disease (COVID-19) and its more severe forms. New-born infants are expected to receive short-term protection from passively transferred maternal antibodies from their mo...

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Autores principales: Mehla, Rajeev, Kokate, Prasad, Bhosale, Sarika R., Vaidya, Vivek, Narayanan, Shridhar, Shandil, Radha. K., Singh, Mayas, Rudramurthy, Gudepalya R., Naveenkumar, Chakenahalli N., Bharathkumar, Kumaraswamy, Coleman, Rob, Mueller, Steffen, Dhere, Rajeev M., Yeolekar, Leena R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965573/
https://www.ncbi.nlm.nih.gov/pubmed/36851133
http://dx.doi.org/10.3390/vaccines11020255
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author Mehla, Rajeev
Kokate, Prasad
Bhosale, Sarika R.
Vaidya, Vivek
Narayanan, Shridhar
Shandil, Radha. K.
Singh, Mayas
Rudramurthy, Gudepalya R.
Naveenkumar, Chakenahalli N.
Bharathkumar, Kumaraswamy
Coleman, Rob
Mueller, Steffen
Dhere, Rajeev M.
Yeolekar, Leena R.
author_facet Mehla, Rajeev
Kokate, Prasad
Bhosale, Sarika R.
Vaidya, Vivek
Narayanan, Shridhar
Shandil, Radha. K.
Singh, Mayas
Rudramurthy, Gudepalya R.
Naveenkumar, Chakenahalli N.
Bharathkumar, Kumaraswamy
Coleman, Rob
Mueller, Steffen
Dhere, Rajeev M.
Yeolekar, Leena R.
author_sort Mehla, Rajeev
collection PubMed
description Children are at risk of infection from severe acute respiratory syndrome coronavirus-2 virus (SARS-CoV-2) resulting in coronavirus disease (COVID-19) and its more severe forms. New-born infants are expected to receive short-term protection from passively transferred maternal antibodies from their mothers who are immunized with first-generation COVID-19 vaccines. Passively transferred antibodies are expected to wane within first 6 months of infant’s life, leaving them vulnerable to COVID-19. Live attenuated vaccines, unlike inactivated or viral-protein-based vaccines, offer broader immune engagement. Given effectiveness of live attenuated vaccines in controlling infectious diseases such as mumps, measles and rubella, we undertook development of a live attenuated COVID-19 vaccine with an aim to vaccinate children beyond 6 months of age. An attenuated vaccine candidate (dCoV), engineered to express sub-optimal codons and deleted polybasic furin cleavage sites in the spike protein of the SARS-CoV-2 WA/1 strain, was developed and tested in hamsters. Hamsters immunized with dCoV via intranasal or intramuscular routes induced high levels of neutralizing antibodies and exhibited complete protection against the SARS-CoV-2 wild-type isolates, i.e., the Wuhan-like (USA-WA1/2020) and Delta variants (B.1.617.2) in a challenge study. In addition, the dCoV formulated with the marketed measles–rubella (MR) vaccine, designated as MR-dCoV, administered to hamsters via intramuscular route, also protected against both SARS-CoV-2 challenges, and dCoV did not interfere with the MR vaccine-mediated immune response. The safety and efficacy of the dCoV and the MR-dCoV against both variants of SARS-CoV-2 opens the possibility of early immunization in children without an additional injection.
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spelling pubmed-99655732023-02-26 A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters Mehla, Rajeev Kokate, Prasad Bhosale, Sarika R. Vaidya, Vivek Narayanan, Shridhar Shandil, Radha. K. Singh, Mayas Rudramurthy, Gudepalya R. Naveenkumar, Chakenahalli N. Bharathkumar, Kumaraswamy Coleman, Rob Mueller, Steffen Dhere, Rajeev M. Yeolekar, Leena R. Vaccines (Basel) Article Children are at risk of infection from severe acute respiratory syndrome coronavirus-2 virus (SARS-CoV-2) resulting in coronavirus disease (COVID-19) and its more severe forms. New-born infants are expected to receive short-term protection from passively transferred maternal antibodies from their mothers who are immunized with first-generation COVID-19 vaccines. Passively transferred antibodies are expected to wane within first 6 months of infant’s life, leaving them vulnerable to COVID-19. Live attenuated vaccines, unlike inactivated or viral-protein-based vaccines, offer broader immune engagement. Given effectiveness of live attenuated vaccines in controlling infectious diseases such as mumps, measles and rubella, we undertook development of a live attenuated COVID-19 vaccine with an aim to vaccinate children beyond 6 months of age. An attenuated vaccine candidate (dCoV), engineered to express sub-optimal codons and deleted polybasic furin cleavage sites in the spike protein of the SARS-CoV-2 WA/1 strain, was developed and tested in hamsters. Hamsters immunized with dCoV via intranasal or intramuscular routes induced high levels of neutralizing antibodies and exhibited complete protection against the SARS-CoV-2 wild-type isolates, i.e., the Wuhan-like (USA-WA1/2020) and Delta variants (B.1.617.2) in a challenge study. In addition, the dCoV formulated with the marketed measles–rubella (MR) vaccine, designated as MR-dCoV, administered to hamsters via intramuscular route, also protected against both SARS-CoV-2 challenges, and dCoV did not interfere with the MR vaccine-mediated immune response. The safety and efficacy of the dCoV and the MR-dCoV against both variants of SARS-CoV-2 opens the possibility of early immunization in children without an additional injection. MDPI 2023-01-24 /pmc/articles/PMC9965573/ /pubmed/36851133 http://dx.doi.org/10.3390/vaccines11020255 Text en © 2023 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
Mehla, Rajeev
Kokate, Prasad
Bhosale, Sarika R.
Vaidya, Vivek
Narayanan, Shridhar
Shandil, Radha. K.
Singh, Mayas
Rudramurthy, Gudepalya R.
Naveenkumar, Chakenahalli N.
Bharathkumar, Kumaraswamy
Coleman, Rob
Mueller, Steffen
Dhere, Rajeev M.
Yeolekar, Leena R.
A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters
title A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters
title_full A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters
title_fullStr A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters
title_full_unstemmed A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters
title_short A Live Attenuated COVID-19 Candidate Vaccine for Children: Protection against SARS-CoV-2 Challenge in Hamsters
title_sort live attenuated covid-19 candidate vaccine for children: protection against sars-cov-2 challenge in hamsters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965573/
https://www.ncbi.nlm.nih.gov/pubmed/36851133
http://dx.doi.org/10.3390/vaccines11020255
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