Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

Shiakolas, Andrea R; Kramer, Kevin J.; Wrapp, Daniel; Richardson, Simone I.; Schäfer, Alexandra; Wall, Steven; Wang, Nianshuang; Janowska, Katarzyna; Pilewski, Kelsey A.; Venkat, Rohit; Parks, Robert; Manamela, Nelia P; Raju, Nagarajan; Fechter, Emilee Friedman; Holt, Clinton; Suryadevara, Naveenchandra; Chen, Rita E.; Martinez, David R.; Nargi, Rachel S.; Sutton, Rachel E.; Ledgerwood, Julie E.; Graham, Barney S.; Diamond, Michael S.; Haynes, Barton F.; Acharya, Priyamvada; Carnahan, Robert H.; Baric, Ralph S.; Morris, Lynn; McLellan, Jason S.; Georgiev, Ivelin S.

doi:10.1016/j.xcrm.2021.100313

Cited by 58 publications

(37 citation statements)

References 59 publications

(68 reference statements)

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“…Cross-reactive antibodies could interact with receptors for the Fc region of antibodies found on the surface of innate immune cells and promote protective effector function activities including antibodydependent cellular phagocytosis and antibody-dependent cellular cytotoxicity [39][40][41] . To this end, a subset of monoclonal antibodies isolated from SARS-CoV patients that were able to cross-react with, but not neutralize SARS-CoV-2 were able to confer protection in a mouse model 42 . Indeed, both passive transfer experiments of monoclonal antibodies [43][44][45][46][47] and evaluation of polyclonal antibodies raised in the context of vaccination or infection [48][49][50] have shown that effector mechanisms contribute to antiviral activity in vivo.…”

Section: Discussionmentioning

confidence: 99%

Boosting of Cross-Reactive Antibodies to Endemic Coronaviruses by SARS-CoV-2 Infection but not Vaccination with Stabilized Spike

Crowley

Natarajan

Hederman

et al. 2021

Preprint

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Pre-existing antibodies to endemic coronaviruses (CoV) that cross-react with SARS-CoV-2 have the potential to influence the antibody response to COVID-19 vaccination and infection for better or worse. In this observational study of mucosal and systemic humoral immunity in acutely infected, convalescent, and vaccinated subjects, we tested for cross reactivity against endemic CoV spike (S) protein at subdomain resolution. Elevated responses, particularly to the β-CoV OC43, were observed in all natural infection cohorts tested and were correlated with the response to SARS-CoV-2. The kinetics of this response and isotypes involved suggest that infection boosts preexisting antibody lineages raised against prior endemic CoV exposure that cross react. While further research is needed to discern whether this recalled response is desirable or detrimental, the boosted antibodies principally targeted the better conserved S2 subdomain of the viral spike and were not associated with neutralization activity. In contrast, vaccination with a stabilized spike mRNA vaccine did not robustly boost cross-reactive antibodies, suggesting differing antigenicity and immunogenicity. In sum, this study provides evidence that antibodies targeting endemic CoV are robustly boosted in response to SARS-CoV-2 infection but not to vaccination with stabilized S, and that depending on conformation or other factors, the S2 subdomain of the spike protein triggers a rapidly recalled, IgG-dominated response that lacks neutralization activity.Graphical AbstractGraphical AbstractAntibody responses to SARS-CoV-2 and endemic CoV spike proteins were measured in diverse cohorts. While antibodies to SARS-CoV-2 were induced across all isotypes, only IgA and IgG responses to endemic CoV were robustly boosted, and only among naturally-infected but not vaccinated individuals. These recalled, cross-reactive responses to endemic CoV primarily recognized the better conserved S2 domain and were non-neutralizing. While other antiviral activities of broadly cross-reactive S2-specifc antibodies are not known, the differing antigenicity of natural infection and vaccination with stabilized pre-fusion spike has potential implications for the breadth and level of protection afforded by each.

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Section: Discussionmentioning

confidence: 99%

Boosting of Cross-Reactive Antibodies to Endemic Coronaviruses by SARS-CoV-2 Infection but not Vaccination with Stabilized Spike

Crowley

Natarajan

Hederman

et al. 2021

Preprint

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“…Increased resistance to SARS-CoV-2 is considered a characteristic feature of children aged 1 to 17 years [ 9 , 22 , 40 ] There are several explanations for this phenomenon. First, the existence of cross-immunity to other β-coronaviruses, weakly pathogenic for humans, has been shown, in particular to HCoV-OC43 and HCoV-HKU1 [ 41 , 42 ]. In addition, children show lower expression of the ACE-2 gene than adults.…”

Section: Methodsmentioning

confidence: 99%

SARS-CoV-2 Seroprevalence Structure of the Russian Population during the COVID-19 Pandemic

Popova

Смирнов

Андреева

et al. 2021

Viruses

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The SARS-CoV-2 pandemic, which came to Russia in March 2020, is accompanied by morbidity level changes and can be tracked using serological monitoring of a representative population sample from Federal Districts (FDs) and individual regions. In a longitudinal cohort study conducted in 26 model regions of Russia, distributed across all FDs, we investigated the distribution and cumulative proportions of individuals with antibodies (Abs) to the SARS-CoV-2 nucleocapsid antigen (Ag), in the period from June to December 2020, using a three-phase monitoring process. In addition, during the formation of the cohort of volunteers, the number of seropositive convalescents, persons who had contact with patients or COVID-19 convalescents, and the prevalence of asymptomatic forms of infection among seropositive volunteers were determined. According to a uniform methodology, 3 mL of blood was taken from the examined individuals, and plasma was separated, from which the presence of Abs to nucleocapsid Ag was determined on a Thermo Scientific Multiascan FC device using the “ELISA anti-SARS-CoV-2 IgG” reagent set (prod. Scientific Center for Applied Microbiology and Biotechnology), in accordance with the developer’s instructions. Volunteers (74,158) were surveyed and divided into seven age groups (1–17, 18–29, 30–39, 40–49, 59–59, 60–69, and 70+ years old), among whom 14,275 were identified as having antibodies to SARS-CoV-2. The average percent seropositive in Russia was 17.8% (IQR: 8.8–23.2). The largest proportion was found among children under 17 years old (21.6% (IQR: 13.1–31.7). In the remaining groups, seroprevalence ranged from 15.6% (IQR: 8–21.1) to 18.0% (IQR: 13.4–22.6). During monitoring, three (immune) response groups were found: (A) groups with a continuous increase in the proportion of seropositive; (B) those with a slow rate of increase in seroprevalence; and (C) those with a two-phase curve, wherein the initial increase was replaced by a decrease in the percentage of seropositive individuals. A significant correlation was revealed between the number of COVID-19 convalescents and contact persons, and between the number of contacts and healthy seropositive volunteers. Among the seropositive volunteers, more than 93.6% (IQR: 87.1–94.9) were asymptomatic. The results show that the COVID-19 pandemic is accompanied by an increase in seroprevalence, which may be important for the formation of herd immunity.

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“…While the effectiveness of the immunization with current mRNA vaccines is undisputable in reducing both infection and disease severity (Haas et al, 2021), public health policies must adapt to rapidly emerging VoCs. The choice of diagnostic tests, vaccine formulations and vaccine deployment will benefit from investigating further the mechanisms influencing the response to vaccination, particularly in view of the ongoing development of pan-coronavirus vaccines (Shiakolas et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Seasonal betacoronavirus antibodies expansion post BNT161b2 vaccination associates with reduced SARS-CoV-2 VoCs neutralization

Dispinseri

Marzinotto

Brigatti

et al. 2021

Preprint

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SARS-CoV-2 vaccination is known to induce antibodies that recognize also variants of concerns (VoCs) of the virus. However, epidemiological and laboratory evidences indicate that these antibodies have a reduce neutralization ability against VoCs. We studied binding and neutralizing antibodies against the Spike RBD and S2 domains of the Wuhan-Hu-1 virus and its alpha and beta VoCs and of seasonal betacoronaviruses (HKU1 and OC43) in a cohort of 31 health care workers vaccinated with BNT162b2-Comirnaty and prospectively followed post-vaccination. The study of sequential samples collected up to 64 days post-vaccination showed that serological assays measuring IgG against Wuhan-Hu-1 antigens were a poor proxy for VoCs neutralization. In addition, in subjects who had asymptomatic or mild COVID-19 prior to vaccination the loss of nAbs following disease can be rapid and protection from re-infection post-vaccination is often no better than in naïve subjects. Interestingly, in health care workers naïve for SARS-CoV-2 infection, vaccination induced a rapid and transient reactivation of pre-existing seasonal coronaviruses IgG responses that was associated with a subsequent reduced ability to neutralize some VoCs.

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Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions

Cited by 58 publications

References 59 publications

Boosting of Cross-Reactive Antibodies to Endemic Coronaviruses by SARS-CoV-2 Infection but not Vaccination with Stabilized Spike

Boosting of Cross-Reactive Antibodies to Endemic Coronaviruses by SARS-CoV-2 Infection but not Vaccination with Stabilized Spike

SARS-CoV-2 Seroprevalence Structure of the Russian Population during the COVID-19 Pandemic

Seasonal betacoronavirus antibodies expansion post BNT161b2 vaccination associates with reduced SARS-CoV-2 VoCs neutralization

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