SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared with SARS-CoV-2 mRNA vaccinations

Anderson, Elizabeth M.; Li, Shuk Hang; Awofolaju, Moses; Eilola, Theresa; Goodwin, Eileen; Bolton, Marcus J.; Gouma, Sigrid; Manzoni, Tomaz B.; Hicks, Philip; Goel, Rishi R.; Painter, Mark M.; Apostolidis, Sokratis A.; Mathew, Divij; Dunbar, Debora; Fiore, Danielle; Brock, Amanda; Weaver, JoEllen; Millar, John S.; DerOhannessian, Stephanie; Greenplate, Allison R.; Frank, Ian; Rader, Daniel J.; Wherry, E. John; Bates, Paul; Hensley, Scott E.

doi:10.1016/j.celrep.2022.111496

Cited by 24 publications

(21 citation statements)

References 80 publications

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“…S5). This is likely related to the more standardized dose ( 24 ) and nature of vaccination compared with infection ( 25 – 27 ) but might also be due to varying time intervals between infection and specimen collection in the convalescent specimens compared with those in postvaccination specimens ( 28 ).…”

Section: Resultsmentioning

confidence: 99%

Mapping SARS-CoV-2 antigenic relationships and serological responses

Wilks,

Mühlemann,

Shen

et al. 2023

Science

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During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns of cross-reactivity among 21 variants and 15 groups of human sera obtained after primary infection with 10 different variants or after messenger RNA (mRNA)–1273 or mRNA-1273.351 vaccination. We found antigenic differences among pre-Omicron variants caused by substitutions at spike-protein positions 417, 452, 484, and 501. Quantifying changes in response breadth over time and with additional vaccine doses, our results show the largest increase between 4 weeks and >3 months after a second dose. We found changes in immunodominance of different spike regions, depending on the variant an individual was first exposed to, with implications for variant risk assessment and vaccine-strain selection.

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Section: Resultsmentioning

confidence: 99%

Mapping SARS-CoV-2 antigenic relationships and serological responses

Wilks,

Mühlemann,

Shen

et al. 2023

Science

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“…The concept of OAS was first described for influenza antibodies (17), with imprinting from prior influenza infections on immune responses following subsequent influenza infection and vaccination noted in more recent work (18)(19)(20). OAS from antibodies generated by prior OC43/HKU1 seasonal coronavirus infections occurs; and is seen more potently following SARS-CoV-2 infection than after the 1st mRNA vaccine dose, with SARS-CoV-2 infection driving a boost of lower affinity antibodies (21). Potentially beneficial imprinting has also been described; omicron breakthrough infections in infection-naive vaccinated individuals induce antibodies from B cells that cross-react with receptor-binding domains from multiple variants and provide a greater breadth of protective immunity whereas antibodies following primary omicron infections in infection-naive unvaccinated individuals are of much narrower specificity (16).…”

Section: Discussionmentioning

confidence: 99%

Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses

Hornsby

Nicols

Longet

et al. 2023

Preprint

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Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in large numbers of individuals with hybrid immunity, generated through a combination of vaccination and infection. Based primarily on circulating neutralizing antibody (NAb) data, concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that a history of prior SARS-CoV-2 in particular is associated with profound immune dampening. Taking a broader and comprehensive approach, we characterized mucosal and blood immunity to both spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without a history of previous SARS-CoV-2 infection. We find that the majority of individuals increase BA.1/BA.2/BA.5-specific NAb following infection, but confirm that the magnitude of increase and post-omicron titres are indeed higher in those who were infection-naive. In contrast, significant increases in nasal antibody responses are seen regardless of prior infection history, including neutralizing activity against BA.5 spike. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are still significantly higher in previously-infected individuals, who appear to have maximally induced responses with a CD8+ phenotype of high cytotoxic potential after their 3rd mRNA vaccine dose. Antibody and T cell responses to non-spike antigens also increase significantly regardless of prior infection status, with a boost seen in previously-infected individuals to immunity primed by their first infection. These findings suggest that hybrid immunity induced by omicron breakthrough infections is highly dynamic, complex, and compartmentalised, with significant immune enhancement that can help protect against COVID-19 caused by future omicron variants.

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“…We also found that antibodies elicited to seasonal coronaviruses to have decreased durability suggesting immunity to seasonal coronaviruses is short-lived as previously reported 12,14,28 . Since only human serological studies on the imprinting effects of seasonal coronaviruses have previously been performed, our study is the first experimental investigation of its kind isolating the immunological impacts of specific coronaviruses 14,[26][27][28][29][61][62][63][64][65][66][67] . Our results bring valuable insight into the specific contributions of preexisting immunity from coronavirus infection and the associated mechanisms of regulation.…”

Section: Discussionmentioning

confidence: 99%

Signatures of Original Antigenic Sin or protection following coronavirus imprinting in Syrian hamsters challenged with SARS-CoV-2 or variants

Francis¹,

Jansen²,

Yourkowski³

et al. 2023

Preprint

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Coronaviruses are a significant threat to public health, animal welfare, and economic stability. SARS-CoV-2 and seasonal coronaviruses continue to cause disease and coronaviruses in the animal reservoir pose a constant spillover threat. Immunological imprinting is a term meant to represent the strong influence of the first viral infection on the outcome of subsequent related viral infections or vaccination, with “Original Antigenic Sin” having historically been applied to the potential negative effects of such imprinting. Little is known, however, about the imprinting potential between seasonal and severe coronaviruses of zoonotic origin and the regulation of cross-reactive responses, positive or negative, upon secondary or subsequent exposures. Here we adopted a step-wise experimental approach to examine the imprinting response and subsequent immune recall toward antigenically distinct coronaviruses at various distances using the Syrian hamster model. This approach enabled the experimental evaluation of cross-reactivity and cross-protection among coronaviruses which has not been previously done. Hamsters were imprinted with seasonal coronaviruses including alphacoronaviruses (HCoV-NL63, HCoV-229E) and betacoronaviruses (HCoV-OC43), or the original SARS-CoV-2 Wuhan virus (also a betacoronavirus). Seasonal CoV imprinting was followed by challenge with the original SARS-CoV-2 Wuhan virus representing distant imprinting-challenge combinations. Wuhan imprinting was followed by homologous Wuhan challenge or heterologous Beta or Omicron variants of concern to assess responses along a continuum of SARS-CoV-2 inter-relatedness. Weight loss and temperature as well as viral load, antibody induction, and host gene profiling for interferon responses, inflammation, and germinal center reactions were analyzed. Although imprinting with seasonal coronaviruses offered little protection against a SARS-CoV-2 Wuhan challenge in terms of viral replication and weight loss, NL63 imprinted animals mounted antigenic sin-like antibody responses while T cell gene signatures were noted in OC43 imprinted animals. The more similar imprinting-challenge regimens led to minimal or no viral replication. Subtle differences in the host responses were noted between Omicron and Beta challenges, suggesting Omicron to be more antigenically distant from Wuhan than the Beta variant. Host gene expression profiling analysis indicated interferon responses and germinal center reactions to be induced during more similar imprinting-challenge combinations while inflammation and antiviral response suppression were signatures in antigenically distant viral challenges. This work is the first characterization and analysis of seasonal coronavirus infection in animals and the subsequent effects on secondary SARS-CoV-2 infection. These results are important for calculating the antigenic distance between coronaviruses and for determining positive or negative cross-reactive signatures. As we begin to construct a matrix of protection, these data may inform the design of pan-coronavirus vaccines and the components needed in a multivalent platform to protect against antigenically distinct groups of coronaviruses while mitigating the risk of negative interference.

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SARS-CoV-2 infections elicit higher levels of original antigenic sin antibodies compared with SARS-CoV-2 mRNA vaccinations

Cited by 24 publications

References 80 publications

Mapping SARS-CoV-2 antigenic relationships and serological responses

Mapping SARS-CoV-2 antigenic relationships and serological responses

Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses

Signatures of Original Antigenic Sin or protection following coronavirus imprinting in Syrian hamsters challenged with SARS-CoV-2 or variants

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