Absence of Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Activity in Prepandemic Sera From Individuals With Recent Seasonal Coronavirus Infection

Poston, Daniel; Weisblum, Yiska; Wise, Helen; Templeton, Kate; Jenks, Sara; Hatziioannou, Théodora; Bieniasz, Paul D.

doi:10.1093/cid/ciaa1803

Cited by 68 publications

(77 citation statements)

References 13 publications

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“…Here, we observed increases in seasonal HCoV spike reactive IgG antibodies in SARS-CoV-2 positive cohort. SARS-CoV-2 has been shown to stimulate OC43 memory B cells through conserved epitopes in the SARS-CoV-2 S glycoprotein S2 subunit and serum samples from subjects with recent HCoV infection contain SARS-CoV-2 cross-reactive but not cross-neutralizing antibodies (54). As de novo IgG cross-reactivity with HCoV-HKU1 and HCoV-OC43 spike protein was not observed in SARS-CoV-2 challenged NHPs (Figure 5A), the presence of prior humoral memory to seasonal HCoV appears necessary to drive cross-reactivity.…”

Section: Discussionmentioning

confidence: 99%

Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses

Laing

et al. 2021

Preprint

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Sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 sero-surveillance. With the rollout of SARS-CoV-2 vaccines, such assays must be able to distinguish vaccine from natural immunity to SARS-CoV-2 and related human coronaviruses. Here, we developed and implemented multiplex microsphere-based immunoassay strategies for COVD-19 antibody studies that incorporates spike protein trimers of SARS-CoV-2 and the endemic seasonal human coronaviruses (HCoV), enabling high throughout measurement of pre-existing cross-reactive antibodies. We varied SARS-CoV-2 antigen compositions within the multiplex assay, allowing direct comparisons of the effects of spike protein, receptor-binding domain protein (RBD) and nucleocapsid protein (NP) based SARS-CoV-2 antibody detection. Multiplex immunoassay performance characteristics are antigen-dependent, and sensitivities and specificities range 92-99% and 94-100%, respectively, for human subject samples collected as early as 7-10 days from symptom onset. SARS-CoV-2 spike and RBD had a strong correlative relationship for the detection of IgG. Correlation between detectable IgG reactive with spike and NP also had strong relationship, however, several PCR-positive and spike IgG-positive serum samples were NP IgG-negative. This spike and NP multiplex immunoassay has the potential to be useful for differentiation between vaccination and natural infection induced antibody responses. We also assessed the induction of de novo SARS-CoV-2 IgG cross reactions with SARS-CoV and MERS-CoV spike proteins. Furthermore, multiplex immunoassays that incorporate spike proteins of SARS-CoV-2 and HCoVs will permit investigations into the influence of HCoV antibodies on COVID-19 clinical outcomes and SARS-CoV-2 antibody durability.

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Section: Discussionmentioning

confidence: 99%

Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses

Laing

et al. 2021

Preprint

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“…Cross-reactivity with seasonal coronaviruses has to be considered. Even if recently, pre-existing HCoV-NL63 antibody response crossreacting with some SARS-CoV-2 antigens was detected in both pre-and mid-pandemic infected individuals [28], though no cross-reactivity of serology methods with the seasonal coronavirus was reported [29] and no neutralizing activity of SARS-CoV-2 in pre-pandemic sera was observed [30]. All IgT-positive serum samples were positive for antibodies against the RBD of S protein (Biosynex COVID19 BSS).…”

Section: Discussionmentioning

confidence: 97%

Seroprevalence of SARS-CoV-2, Symptom Profiles and Sero-Neutralization in a Suburban Area, France

Petit

Jeulin

Legrand

et al. 2021

Viruses

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The World Health Organisation recommends monitoring the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated anti–SARS-CoV-2 total immunoglobulin (IgT) antibody seroprevalence and in vitro sero-neutralization in Nancy, France, in spring 2020. Individuals were randomly sampled from electoral lists and invited with household members over 5 years old to be tested for anti–SARS-CoV-2 (IgT, i.e., IgA/IgG/IgM) antibodies by ELISA (Bio-rad); the sero-neutralization activity was evaluated on Vero CCL-81 cells. Among 2006 individuals, the raw seroprevalence was 2.1% (95% confidence interval 1.5 to 2.9), was highest for 20- to 34-year-old participants (4.7% (2.3 to 8.4)), within than out of socially deprived area (2.5% vs. 1%, p = 0.02) and with than without intra-family infection (p < 10−6). Moreover, 25% of participants presented at least one COVID-19 symptom associated with SARS-CoV-2 positivity (p < 10−13), with highly discriminant anosmia or ageusia (odds ratio 27.8 [13.9 to 54.5]); 16.3% (6.8 to 30.7) of seropositive individuals were asymptomatic. Positive sero-neutralization was demonstrated in vitro for 31/43 seropositive subjects. Regarding the very low seroprevalence, a preventive effect of the lockdown in March 2020 can be assumed for the summer, but a second COVID-19 wave, as expected, could be subsequently observed in this poorly immunized population.

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“…While some studies have found that these cross-reactive antibodies can neutralize SARS-CoV-2 in vitro, others have not (61,91,92). In patients, cross-reactive antibodies are also not associated with protection against SARS-CoV-2 infection or severe COVID-19 (61).…”

Section: Discussionmentioning

confidence: 99%

High-affinity, neutralizing antibodies to SARS-CoV-2 can be made in the absence of T follicular helper cells

Chen

Chow

Song

et al. 2021

Preprint

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T follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 as well as influenza A virus. Tfh-independent responses were mediated by a population we call lymph node (LN)-Th1 cells, which remain in the LN and interact with B cells outside of GCs to promote high-affinity but broad-spectrum antibodies. Strikingly, antibodies generated in the presence and absence of Tfh cells displayed similar neutralization potency against homologous SARS-CoV-2 as well as the B.1.351 variant of concern. These data support a new paradigm for the induction of B cell responses during viral infection that enables effective, neutralizing antibody production to complement traditional GCs and even compensate for GCs damaged by viral inflammation.

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Absence of Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Activity in Prepandemic Sera From Individuals With Recent Seasonal Coronavirus Infection

Cited by 68 publications

References 13 publications

Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses

Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses

Seroprevalence of SARS-CoV-2, Symptom Profiles and Sero-Neutralization in a Suburban Area, France

High-affinity, neutralizing antibodies to SARS-CoV-2 can be made in the absence of T follicular helper cells

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