Original antigenic sin responses to Betacoronavirus spike proteins are observed in a mouse model, but are not apparent in children following SARS-CoV-2 infection

Lapp, Stacey A.; Edara, Venkata Viswanadh; Lu, Austin; Lai, Lilin; Hussaini, Laila; Chahroudi, Ann; Anderson, Larry J.; Suthar, Mehul S.; Anderson, Evan J.; Rostad, Christina A.

doi:10.1371/journal.pone.0256482

Cited by 19 publications

(15 citation statements)

References 24 publications

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“…Recently, we observed anti-S2 cross-reactivity in naive older children but not in the younger children (<4 years old), who share homology with HKU1, 229E, and OC43 23 , 24 . OAS was also observed in mice immunization studies with seasonal CoV followed by SARS-CoV-2 spike 25 . Most of these cross-reactive antibodies do not neutralize SARS-CoV-2, as was observed with samples from 10 children with seasonal CoVs in our study.…”

Section: Discussionmentioning

confidence: 72%

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

et al. 2022

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Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5–11, 12–21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.

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Section: Discussionmentioning

confidence: 72%

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

et al. 2022

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“…The original antigenic sin hypothesis suggests that preexisting immunity results in the reactivation of a response to an earlier strain, as opposed to the formation of an unbiased response against the current strain. While this recall could offer temporal advantages, it may reduce the formation of neutralizing antibodies, thereby dampening effective clearance of the novel virus, as has recently been reported in mouse models ( Lapp et al, 2021 ; Lin et al, 2022 ). Seminal studies of responses to influenza, based on epidemiology, modeling, and repertoire profiling, suggest that the antibodies generated from childhood exposure to influenza are ‘imprinted’ and exert a major influence on the nature of the antibody response elicited upon subsequent exposures in humans ( Francis et al, 1947 ; Fonville et al, 2014 ; Kucharski et al, 2015 ; Gostic et al, 2016 ; Lee et al, 2019 ).…”

Section: Discussionmentioning

confidence: 97%

Boosting of cross-reactive antibodies to endemic coronaviruses by SARS-CoV-2 infection but not vaccination with stabilized spike

Crowley

Natarajan

Hederman

et al. 2022

eLife

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Preexisting 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.

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“…To this end, the relationship between ADE and COVID-19 has been assessed (Lee et al, 2020). However, recent reports demonstrated that, although similar phenomena have been observed in mice, stronger evidence is required to confirm whether ADE and original antigenic sin can affect vaccination and human resistance against the virus (Lapp et al, 2021;Vashishtha, 2021).…”

Section: Discussionmentioning

confidence: 99%

Seasonal coronaviruses and SARS-CoV-2: effects of preexisting immunity during the COVID-19 pandemic

Wang

Xiang

Wang

et al. 2022

J. Zhejiang Univ. Sci. B

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Although the coronavirus disease 2019 (COVID-19) epidemic is still ongoing, vaccination rates are rising slowly and related treatments and drugs are being developed. At the same time, there is increasing evidence of preexisting immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in humans, mainly consisting of preexisting antibodies and immune cells (including T cells and B cells). The presence of these antibodies is mainly due to the seasonal prevalence of four common coronavirus types, especially OC43 and HKU1. The accumulated relevant evidence has suggested that the target of antibodies is mainly the S2 subunit of S protein, followed by evolutionary conservative regions such as the nucleocapsid (N) protein. Additionally, preexisting memory T and B cells are also present in the population. Preexisting antibodies can help the body protect against SARS-CoV-2 infection, reduce the severity of COVID-19, and rapidly increase the immune response post-infection. These multiple effects can directly affect disease progression and even the likelihood of death in certain individuals. Besides the positive effects, preexisting immunity may also have negative consequences, such as antibody-dependent enhancement (ADE) and original antigenic sin (OAS), the prevalence of which needs to be further established. In the future, more research should be focused on evaluating the role of preexisting immunity in COVID-19 outcomes, adopting appropriate policies and strategies for fighting the pandemic, and vaccine development that considers preexisting immunity.

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Original antigenic sin responses to Betacoronavirus spike proteins are observed in a mouse model, but are not apparent in children following SARS-CoV-2 infection

Cited by 19 publications

References 24 publications

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

Boosting of cross-reactive antibodies to endemic coronaviruses by SARS-CoV-2 infection but not vaccination with stabilized spike

Seasonal coronaviruses and SARS-CoV-2: effects of preexisting immunity during the COVID-19 pandemic

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