Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

Zhu, Yuanmei; Yu, Danwei; Han, Yang; Huang, Yan; Chong, Huihui; Ren, Lili; Wang, Jianwei; Li, Taisheng; He, Yuxian

doi:10.1126/sciadv.abc9999

Cited by 59 publications

(40 citation statements)

References 40 publications

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“…7B). There is also substantial correlation between binding to RBD and to these S variants (p between 0.75 and 0.8), suggesting that the RBD contains immunodominant epitopes, consistent with observations using human sera (Piccoli et al 2020;Yu et al 2020;Zhu et al 2020). In contrast, there is poor correlation (p<0.5) between the binding of individual sera to S-R/x2 and to the other S variants or RBD.…”

Section: Trimeric S Constructs All Induce Antibodies That Bind S Conssupporting

confidence: 84%

SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses

Carnell

Ciazynska

Wells

et al. 2021

Preprint

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The majority of SARS-CoV-2 vaccines in use or in advanced clinical development are based on the viral spike protein (S) as their immunogen. S is present on virions as pre-fusion trimers in which the receptor binding domain (RBD) is stochastically open or closed. Neutralizing antibodies have been described that act against both open and closed conformations. The long-term success of vaccination strategies will depend upon inducing antibodies that provide long-lasting broad immunity against evolving, circulating SARS-CoV-2 strains, while avoiding the risk of antibody dependent enhancement as observed with other Coronavirus vaccines. Here we have assessed the results of immunization in a mouse model using an S protein trimer that is arrested in the closed state to prevent exposure of the receptor binding site and therefore interaction with the receptor. We compared this with a range of other modified S protein constructs, including representatives used in current vaccines. We found that all trimeric S proteins induce a long-lived, strongly neutralizing antibody response as well as T-cell responses. Notably, the protein binding properties of sera induced by the closed spike differed from those induced by standard S protein constructs. Closed S proteins induced more potent neutralising responses than expected based on the degree to which they inhibit interactions between the RBD and ACE2. These observations suggest that closed spikes recruit different, but equally potent, virus-inhibiting immune responses than open spikes, and that this is likely to include neutralizing antibodies against conformational epitopes present in the closed conformation. Together with their improved stability and storage properties we suggest that closed spikes may be a valuable component of refined, next-generation vaccines.

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Section: Trimeric S Constructs All Induce Antibodies That Bind S Conssupporting

confidence: 84%

SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses

Carnell

Ciazynska

Wells

et al. 2021

Preprint

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“…Murine SARS-CoV S antibodies can inhibit SARS-CoV-2 cell entry, consistent with the similarities of the S protein between the two viruses (66). Serum from SARS-CoV recovered individuals during the 2003 outbreak has been shown to cross-react with the S ectodomain, S, RBD and S2 proteins of SARS-CoV-2 and neutralise SARS-CoV-2 in vitro (67,68). More recently, RBD-targeting antibodies have been isolated in convalescent SARS-CoV plasma and were shown to cross-neutralise SARS-CoV-2 by targeting multiple conserved epitopes on the S protein (69).…”

Section: Neutralising Antibodies and Cross-neutralisationsupporting

confidence: 65%

Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)

2020

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In December 2019, an outbreak of a novel coronavirus (SARS-CoV-2) in Wuhan, China resulted in the current COVID-19 global pandemic. The human immune system has not previously encountered this virus, raising the important question as to whether or not protective immunity is generated by infection. Growing evidence suggests that protective immunity can indeed be acquired post-infection—although a handful of reinfection cases have been reported. However, it is still unknown whether the immune response to SARS-CoV-2 leads to some degree of long-lasting protection against the disease or the infection. This review draws insights from previous knowledge regarding the nature and longevity of immunity to the related virus, SARS-CoV, to fill the gaps in our understanding of the immune response to SARS-CoV-2. Deciphering the immunological characteristics that give rise to protective immunity against SARS-CoV-2 is critical to guiding vaccine development and also predicting the course of the pandemic. Here we discuss the recent evidence that characterises the adaptive immune response against SARS-CoV-2 and its potential implications for the generation of memory responses and long-term protection.

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“…Anti-SARS-CoV-2 S protein antibodies neutralize SARS-CoV S protein pseudotyped viral particles (Prevost et al, 2020). Importantly, convalescent serum samples collected from the 2003 SARS outbreak cross-reacted with the S protein of SARS-CoV-2 and neutralized SARS-CoV-2 infection (Zhu et al, 2020c). Thus, neutralizing antibodies to SARS-CoV-2 were readily produced in COVID-19 patients.…”

Section: Structural and Neutralizing Properties Of Anti-sars-cov-2 Anmentioning

confidence: 98%

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

Zhang

Zhan

et al. 2020

Sci. China Life Sci.

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The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

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Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals

Cited by 59 publications

References 40 publications

SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses

SARS-CoV-2 spike protein arrested in the closed state induces potent neutralizing responses

Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

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