Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron

Abstract The continuing evolution of SARS-CoV-2 variants challenges the durability of existing spike (S)-based COVID-19 vaccines. We hypothesized that vaccines composed of both S and nucleocapsid (N) antigens would increase the durability of protection by strengthening and broadening cellular immuni...

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Main Authors: Paolla Beatriz Almeida Pinto, Julia Timis, Kantinan Chuensirikulchai, Qin Hui Li, Hsueh Han Lu, Erin Maule, Michael Nguyen, Rúbens Prince dos Santos Alves, Shailendra Kumar Verma, Fernanda Ana-Sosa-Batiz, Kristen Valentine, Sara Landeras-Bueno, Kenneth Kim, Kathryn Hastie, Erica Ollmann Saphire, Ada Alves, Annie Elong Ngono, Sujan Shresta
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-024-01043-3
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author Paolla Beatriz Almeida Pinto
Julia Timis
Kantinan Chuensirikulchai
Qin Hui Li
Hsueh Han Lu
Erin Maule
Michael Nguyen
Rúbens Prince dos Santos Alves
Shailendra Kumar Verma
Fernanda Ana-Sosa-Batiz
Kristen Valentine
Sara Landeras-Bueno
Kenneth Kim
Kathryn Hastie
Erica Ollmann Saphire
Ada Alves
Annie Elong Ngono
Sujan Shresta
author_facet Paolla Beatriz Almeida Pinto
Julia Timis
Kantinan Chuensirikulchai
Qin Hui Li
Hsueh Han Lu
Erin Maule
Michael Nguyen
Rúbens Prince dos Santos Alves
Shailendra Kumar Verma
Fernanda Ana-Sosa-Batiz
Kristen Valentine
Sara Landeras-Bueno
Kenneth Kim
Kathryn Hastie
Erica Ollmann Saphire
Ada Alves
Annie Elong Ngono
Sujan Shresta
author_sort Paolla Beatriz Almeida Pinto
collection DOAJ
description Abstract The continuing evolution of SARS-CoV-2 variants challenges the durability of existing spike (S)-based COVID-19 vaccines. We hypothesized that vaccines composed of both S and nucleocapsid (N) antigens would increase the durability of protection by strengthening and broadening cellular immunity compared with S-based vaccines. To test this, we examined the immunogenicity and efficacy of wild-type SARS-CoV-2 S- and N-based DNA vaccines administered individually or together to K18-hACE2 mice. S, N, and S + N vaccines all elicited polyfunctional CD4+ and CD8+ T cell responses and provided short-term cross-protection against Beta and Omicron BA.2 variants, but only co-immunization with S + N vaccines provided long-term protection against Omicron BA.2. Depletion of CD4+ and CD8+ T cells reduced the long-term efficacy, demonstrating a crucial role for T cells in the durability of protection. These findings underscore the potential to enhance long-lived protection against SARS-CoV-2 variants by combining S and N antigens in next-generation COVID-19 vaccines.
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publishDate 2024-12-01
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spelling doaj-art-2a875f4f5f724a3c9cd423ad07c07eb12024-12-22T12:13:14ZengNature Portfolionpj Vaccines2059-01052024-12-019111510.1038/s41541-024-01043-3Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 OmicronPaolla Beatriz Almeida Pinto0Julia Timis1Kantinan Chuensirikulchai2Qin Hui Li3Hsueh Han Lu4Erin Maule5Michael Nguyen6Rúbens Prince dos Santos Alves7Shailendra Kumar Verma8Fernanda Ana-Sosa-Batiz9Kristen Valentine10Sara Landeras-Bueno11Kenneth Kim12Kathryn Hastie13Erica Ollmann Saphire14Ada Alves15Annie Elong Ngono16Sujan Shresta17Center for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyLaboratory of Biotechnology and Physiology of Viral Infections, Oswaldo Cruz Institute, FiocruzCenter for Vaccine Innovation, La Jolla Institute for ImmunologyCenter for Vaccine Innovation, La Jolla Institute for ImmunologyAbstract The continuing evolution of SARS-CoV-2 variants challenges the durability of existing spike (S)-based COVID-19 vaccines. We hypothesized that vaccines composed of both S and nucleocapsid (N) antigens would increase the durability of protection by strengthening and broadening cellular immunity compared with S-based vaccines. To test this, we examined the immunogenicity and efficacy of wild-type SARS-CoV-2 S- and N-based DNA vaccines administered individually or together to K18-hACE2 mice. S, N, and S + N vaccines all elicited polyfunctional CD4+ and CD8+ T cell responses and provided short-term cross-protection against Beta and Omicron BA.2 variants, but only co-immunization with S + N vaccines provided long-term protection against Omicron BA.2. Depletion of CD4+ and CD8+ T cells reduced the long-term efficacy, demonstrating a crucial role for T cells in the durability of protection. These findings underscore the potential to enhance long-lived protection against SARS-CoV-2 variants by combining S and N antigens in next-generation COVID-19 vaccines.https://doi.org/10.1038/s41541-024-01043-3
spellingShingle Paolla Beatriz Almeida Pinto
Julia Timis
Kantinan Chuensirikulchai
Qin Hui Li
Hsueh Han Lu
Erin Maule
Michael Nguyen
Rúbens Prince dos Santos Alves
Shailendra Kumar Verma
Fernanda Ana-Sosa-Batiz
Kristen Valentine
Sara Landeras-Bueno
Kenneth Kim
Kathryn Hastie
Erica Ollmann Saphire
Ada Alves
Annie Elong Ngono
Sujan Shresta
Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron
npj Vaccines
title Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron
title_full Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron
title_fullStr Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron
title_full_unstemmed Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron
title_short Co-immunization with spike and nucleocapsid based DNA vaccines for long-term protective immunity against SARS-CoV-2 Omicron
title_sort co immunization with spike and nucleocapsid based dna vaccines for long term protective immunity against sars cov 2 omicron
url https://doi.org/10.1038/s41541-024-01043-3
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