SARS-CoV-2 infection protects against rechallenge in rhesus macaques

Chandrashekar, Abishek; Liu, Jinyan; Martinot, Amanda J.; McMahan, Katherine; Mercado, Noe B.; Peter, Lauren; Tostanoski, Lisa H.; Yu, Jingyou; Maliga, Zoltan; Nekorchuk, Michael; Busman‐Sahay, Kathleen; Terry, Margaret; Wrijil, Linda M.; Ducat, Sarah; Martinez, David R.; Atyeo, Caroline; Fischinger, Stephanie; Burke, John S.; Slein, Matthew D.; Pessaint, Laurent; Ry, Alex Van; Greenhouse, Jack; Taylor, Tammy; Blade, Kelvin; Cook, Anthony; Finneyfrock, Brad; Brown, Renita; Teow, Elyse; Velasco, Jason; Zahn, Roland; Wegmann, Frank; Abbink, Peter; Bondzie, Esther A.; Dagotto, Gabriel; Gebre, Makda S.; He, Xuan; Jacob-Dolan, Catherine; Kordana, Nicole; Li, Zhenfeng; Lifton, Michelle A.; Mahrokhian, Shant H.; Maxfield, Lori F.; Nityanandam, Ramya; Nkolola, Joseph P.; Schmidt, Aaron; Miller, Andrew D.; Baric, Ralph S.; Alter, Galit; Sorger, Peter K.; Estes, Jacob D.; Andersen, Hanné; Lewis, Mark G.; Barouch, Dan H.

doi:10.1126/science.abc4776

Cited by 861 publications

(1,109 citation statements)

References 20 publications

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“…There have been anecdotal accounts suggesting that immunity generated from an initial SARS-CoV-2 infection in humans may not be protective against a subsequent infection. Recent studies using nonhuman primates indicated prior infection results in protective immunity (19). Here, we…”

Section: Discussionmentioning

confidence: 73%

“…The ongoing pandemic has led to the search for animal models faithfully recapitulating salient features of human coronavirus disease (COVID- 19) for pathogenesis studies and evaluation of vaccines and therapeutics (1). Early reports indicated that Syrian hamsters, whose ACE2 is highly homologous to its human ortholog, were highly susceptible to SARS-CoV-2 infection but did not develop severe disease (2,3).…”

Section: Main Textmentioning

confidence: 99%

See 1 more Smart Citation

Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters

Brocato¹,

Principe²,

Kimi³

et al. 2020

Preprint

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Animal models recapitulating human COVID-19 disease, especially with severe disease, are urgently needed to understand pathogenesis and evaluate candidate vaccines and therapeutics. Here, we develop novel severe disease animal models for COVID-19 involving disruption of adaptive immunity in Syrian hamsters. Cyclophosphamide (CyP) immunosuppressed or RAG2 knockout (KO) hamsters were exposed to SARS-CoV-2 by the respiratory route. Both the CyP-treated and RAG2 KO hamsters developed clinical signs of disease that were more severe than in immunocompetent hamsters, notably weight loss, viral loads, and fatality (RAG2 KO only). Disease was prolonged in transiently immunosuppressed hamsters and uniformly lethal in RAG2 KO hamsters. We evaluated the protective efficacy of a neutralizing monoclonal antibody and found that pretreatment, even in immunosuppressed animals, limited infection. Our results suggest that functional B and/or T cells are not only important for the clearance of SARS-CoV-2, but also play an early role in protection from acute disease.

show abstract

Section: Discussionmentioning

confidence: 73%

Section: Main Textmentioning

confidence: 99%

Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters

Brocato¹,

Principe²,

Kimi³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…During the SARS and MERS outbreaks, NHP models were developed with a moderate degree of success 3 . Early reports also indicate the utility of NHPs for SARS-CoV-2 infection, and for evaluating vaccine candidates 4, 5, 6, 7 . We hypothesized that the heterogeneity of human responses to SARS-CoV-2 infection can be recapitulated using multiple NHP species.…”

Section: Mainmentioning

confidence: 99%

SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species

Singh

Ganatra

Singh

et al. 2020

Preprint

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SummaryThere are no known cures or vaccines for COVID-19, the defining pandemic of this era. Animal models are essential to fast track new interventions and nonhuman primate (NHP) models of other infectious diseases have proven extremely valuable. Here we compare SARS-CoV-2 infection in three species of experimentally infected NHPs (rhesus macaques, baboons, and marmosets). During the first 3 days, macaques developed clinical signatures of viral infection and systemic inflammation, coupled with early evidence of viral replication and mild-to-moderate interstitial and alveolar pneumonitis, as well as extra-pulmonary pathologies. Cone-beam CT scans showed evidence of moderate pneumonia, which progressed over 3 days. Longitudinal studies showed that while both young and old macaques developed early signs of COVID-19, both groups recovered within a two-week period. Recovery was characterized by low-levels of viral persistence in the lung, suggesting mechanisms by which individuals with compromised immune systems may be susceptible to prolonged and progressive COVID-19. The lung compartment contained a complex early inflammatory milieu with an influx of innate and adaptive immune cells, particularly interstitial macrophages, neutrophils and plasmacytoid dendritic cells, and a prominent Type I-interferon response. While macaques developed moderate disease, baboons exhibited prolonged shedding of virus and extensive pathology following infection; and marmosets demonstrated a milder form of infection. These results showcase in critical detail, the robust early cellular immune responses to SARS-CoV-2 infection, which are not sterilizing and likely impact development of antibody responses. Thus, various NHP genera recapitulate heterogeneous progression of COVID-19. Rhesus macaques and baboons develop different, quantifiable disease attributes making them immediately available essential models to test new vaccines and therapies.

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“…This has important implications for COVID-19 vaccine development as virus-specific T cells are thought to play an important role in SARS-CoV-2 infection [18][19][20][21][22] . While no correlate of protection has been defined for COVID-19, recent publications suggest that neutralising antibody titres may be correlated with protection in animal challenge models 23,24 . A single dose of ChAdOx1 nCoV-19 induces antibody responses, but we demonstrate here that antibody responses are significantly enhanced after homologous boost in one mouse strain and to a greater extent in pigs.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

Graham

McLean

Spencer

et al. 2020

Preprint

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Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replicationdeficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.

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SARS-CoV-2 infection protects against rechallenge in rhesus macaques

Cited by 861 publications

References 20 publications

Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters

Disruption of Adaptive Immunity Enhances Disease in SARS-CoV-2 Infected Syrian Hamsters

SARS-CoV-2 infection leads to acute infection with dynamic cellular and inflammatory flux in the lung that varies across nonhuman primate species

Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

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