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Protective Efficacy of Rhesus Adenovirus COVID-19 Vaccines against Mouse-Adapted SARS-CoV-2.
Tostanoski, Lisa H; Gralinski, Lisa E; Martinez, David R; Schaefer, Alexandra; Mahrokhian, Shant H; Li, Zhenfeng; Nampanya, Felix; Wan, Huahua; Yu, Jingyou; Chang, Aiquan; Liu, Jinyan; McMahan, Katherine; Ventura, John D; Dinnon, Kenneth H; Leist, Sarah R; Baric, Ralph S; Barouch, Dan H.
  • Tostanoski LH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Gralinski LE; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
  • Martinez DR; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
  • Schaefer A; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
  • Mahrokhian SH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Li Z; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Nampanya F; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Wan H; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Yu J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Chang A; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Liu J; Harvard Medical School, Boston, Massachusetts, USA.
  • McMahan K; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Ventura JD; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Dinnon KH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Centergrid.239395.7, Harvard Medical School, Boston, Massachusetts, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
  • Barouch DH; Department of Epidemiology, University of North Carolina at Chapel Hillgrid.10698.36, Chapel Hill, North Carolina, USA.
J Virol ; 95(23): e0097421, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1410203
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ABSTRACT
The global COVID-19 pandemic has sparked intense interest in the rapid development of vaccines as well as animal models to evaluate vaccine candidates and to define immune correlates of protection. We recently reported a mouse-adapted SARS-CoV-2 virus strain (MA10) with the potential to infect wild-type laboratory mice, driving high levels of viral replication in respiratory tract tissues as well as severe clinical and respiratory symptoms, aspects of COVID-19 disease in humans that are important to capture in model systems. We evaluated the immunogenicity and protective efficacy of novel rhesus adenovirus serotype 52 (RhAd52) vaccines against MA10 challenge in mice. Baseline seroprevalence is lower for rhesus adenovirus vectors than for human or chimpanzee adenovirus vectors, making these vectors attractive candidates for vaccine development. We observed that RhAd52 vaccines elicited robust binding and neutralizing antibody titers, which inversely correlated with viral replication after challenge. These data support the development of RhAd52 vaccines and the use of the MA10 challenge virus to screen novel vaccine candidates and to study the immunologic mechanisms that underscore protection from SARS-CoV-2 challenge in wild-type mice. IMPORTANCE We have developed a series of SARS-CoV-2 vaccines using rhesus adenovirus serotype 52 (RhAd52) vectors, which exhibit a lower seroprevalence than human and chimpanzee vectors, supporting their development as novel vaccine vectors or as an alternative adenovirus (Ad) vector for boosting. We sought to test these vaccines using a recently reported mouse-adapted SARS-CoV-2 (MA10) virus to (i) evaluate the protective efficacy of RhAd52 vaccines and (ii) further characterize this mouse-adapted challenge model and probe immune correlates of protection. We demonstrate that RhAd52 vaccines elicit robust SARS-CoV-2-specific antibody responses and protect against clinical disease and viral replication in the lungs. Further, binding and neutralizing antibody titers correlated with protective efficacy. These data validate the MA10 mouse model as a useful tool to screen and study novel vaccine candidates, as well as the development of RhAd52 vaccines for COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Pandemics / Adenovirus Vaccines / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: J Virol Year: 2021 Document Type: Article Affiliation country: JVI.00974-21

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Pandemics / Adenovirus Vaccines / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Observational study / Prognostic study Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: J Virol Year: 2021 Document Type: Article Affiliation country: JVI.00974-21