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Sci Transl Med ; 13(618): eabj3789, 2021 Nov 03.
Article in English | MEDLINE | ID: covidwho-1494936


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern have emerged and may pose a threat to both the efficacy of vaccines based on the original WA1/2020 strain and the natural immunity induced by infection with earlier SARS-CoV-2 variants. We investigated how mutations in the spike protein of circulating SARS-CoV-2 variants, which have been shown to partially evade neutralizing antibodies, affect natural and vaccine-induced immunity. We adapted a Syrian hamster model of moderate to severe clinical disease for two variant strains of SARS-CoV-2: B.1.1.7 (alpha variant) and B.1.351 (beta variant). We then assessed the protective efficacy conferred by either natural immunity from WA1/2020 infection or by vaccination with a single dose of the adenovirus serotype 26 vaccine, Ad26.COV2.S. Primary infection with the WA1/2020 strain provided potent protection against weight loss and viral replication in lungs after rechallenge with WA1/2020, B.1.1.7, or B.1.351. Ad26.COV2.S induced cross-reactive binding and neutralizing antibodies that were reduced against the B.1.351 strain compared with WA1/2020 but nevertheless still provided robust protection against B.1.351 challenge, as measured by weight loss and pathology scoring in the lungs. Together, these data support hamsters as a preclinical model to study protection against emerging variants of SARS-CoV-2 conferred by prior infection or vaccination.

COVID-19 , SARS-CoV-2 , Animals , COVID-19 Vaccines , Cricetinae , Humans , Vaccination
Nat Med ; 26(11): 1694-1700, 2020 11.
Article in English | MEDLINE | ID: covidwho-744383


Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1-4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5-7 and nonhuman primates8-10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11-13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.

Adenoviridae/genetics , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Adenoviridae/immunology , Animals , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/therapeutic use , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , COVID-19 Vaccines/genetics , Cricetinae , Disease Models, Animal , Female , Genetic Vectors , Humans , Male , Mesocricetus , SARS-CoV-2/genetics , Severity of Illness Index , Vaccines, Synthetic/genetics , Vaccines, Synthetic/therapeutic use , Viral Load
Science ; 369(6505): 812-817, 2020 08 14.
Article in English | MEDLINE | ID: covidwho-327276


An understanding of protective immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for vaccine and public health strategies aimed at ending the global coronavirus disease 2019 (COVID-19) pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against reexposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. After the initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with after the primary infection. Anamnestic immune responses after rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against reexposure in nonhuman primates.

Betacoronavirus , Coronavirus Infections/immunology , Pneumonia, Viral/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Betacoronavirus/immunology , Betacoronavirus/physiology , Bronchoalveolar Lavage Fluid/virology , COVID-19 , Coronavirus Infections/pathology , Coronavirus Infections/virology , Disease Models, Animal , Female , Immunity, Cellular , Immunity, Humoral , Immunologic Memory , Lung/immunology , Lung/pathology , Lung/virology , Lung Diseases, Interstitial/immunology , Lung Diseases, Interstitial/pathology , Lung Diseases, Interstitial/virology , Macaca mulatta , Male , Nasal Mucosa/virology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/virology , Recurrence , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology , Viral Load , Virus Replication