Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity

Abstract The objective of this study is to further analyze recombinant rabies virus-vectored SARS-CoV-2 vaccine, CORAVAX, as an effective COVID-19 vaccine strategy. CORAVAX has proven immunogenic and protective against SARS-CoV-2 in animal models. Here, we have screened adjuvants for the highest qua...

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Main Authors: Catherine Yankowski, Christoph Wirblich, Drishya Kurup, Matthias J. Schnell
Format: Article
Language:English
Published: Nature Portfolio 2022-09-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-022-00532-7
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author Catherine Yankowski
Christoph Wirblich
Drishya Kurup
Matthias J. Schnell
author_facet Catherine Yankowski
Christoph Wirblich
Drishya Kurup
Matthias J. Schnell
author_sort Catherine Yankowski
collection DOAJ
description Abstract The objective of this study is to further analyze recombinant rabies virus-vectored SARS-CoV-2 vaccine, CORAVAX, as an effective COVID-19 vaccine strategy. CORAVAX has proven immunogenic and protective against SARS-CoV-2 in animal models. Here, we have screened adjuvants for the highest quality antibody titers, negated the concern of pre-existing rabies-vector immunity, and established its potential as a long-term COVID-19 vaccine. We have tested toll-like receptor 4 (TLR4) agonists, inflammasome activators, and alum adjuvants in CORAVAX and found TLR4-activating MPLA-AddaVax to have the greatest potential. We followed the humoral immune response to CORAVAX in mice with pre-existing rabies virus immunity and saw no significant differences compared to naive mice. We then followed the immune response to CORAVAX over several months and 1-year post-immunization. Mice maintained high antigen-specific serum antibody titers as well as long-lived antibody-secreting cells in the spleen and bone marrow. We believe this rabies-vector strategy combats the problem of waning immunity of other COVID-19 vaccines. These results together support CORAVAX’s potential during the ongoing COVID-19 pandemic.
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spelling doaj.art-2752e4a5f5ff490aa1b582118b8383c92023-11-02T06:36:40ZengNature Portfolionpj Vaccines2059-01052022-09-017111110.1038/s41541-022-00532-7Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunityCatherine Yankowski0Christoph Wirblich1Drishya Kurup2Matthias J. Schnell3Department of Microbiology and Immunology, Sidney Kimmel Medical College at Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College at Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College at Thomas Jefferson UniversityDepartment of Microbiology and Immunology, Sidney Kimmel Medical College at Thomas Jefferson UniversityAbstract The objective of this study is to further analyze recombinant rabies virus-vectored SARS-CoV-2 vaccine, CORAVAX, as an effective COVID-19 vaccine strategy. CORAVAX has proven immunogenic and protective against SARS-CoV-2 in animal models. Here, we have screened adjuvants for the highest quality antibody titers, negated the concern of pre-existing rabies-vector immunity, and established its potential as a long-term COVID-19 vaccine. We have tested toll-like receptor 4 (TLR4) agonists, inflammasome activators, and alum adjuvants in CORAVAX and found TLR4-activating MPLA-AddaVax to have the greatest potential. We followed the humoral immune response to CORAVAX in mice with pre-existing rabies virus immunity and saw no significant differences compared to naive mice. We then followed the immune response to CORAVAX over several months and 1-year post-immunization. Mice maintained high antigen-specific serum antibody titers as well as long-lived antibody-secreting cells in the spleen and bone marrow. We believe this rabies-vector strategy combats the problem of waning immunity of other COVID-19 vaccines. These results together support CORAVAX’s potential during the ongoing COVID-19 pandemic.https://doi.org/10.1038/s41541-022-00532-7
spellingShingle Catherine Yankowski
Christoph Wirblich
Drishya Kurup
Matthias J. Schnell
Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity
npj Vaccines
title Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity
title_full Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity
title_fullStr Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity
title_full_unstemmed Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity
title_short Inactivated rabies-vectored SARS-CoV-2 vaccine provides long-term immune response unaffected by vector immunity
title_sort inactivated rabies vectored sars cov 2 vaccine provides long term immune response unaffected by vector immunity
url https://doi.org/10.1038/s41541-022-00532-7
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AT christophwirblich inactivatedrabiesvectoredsarscov2vaccineprovideslongtermimmuneresponseunaffectedbyvectorimmunity
AT drishyakurup inactivatedrabiesvectoredsarscov2vaccineprovideslongtermimmuneresponseunaffectedbyvectorimmunity
AT matthiasjschnell inactivatedrabiesvectoredsarscov2vaccineprovideslongtermimmuneresponseunaffectedbyvectorimmunity