Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period

Dawen, Esther; Narowski, Tara M.; Wang, Eric; Garrigan, Emily; Mateus, José; Weiskopf, Daniela; Grifoni, Alba; Premkumar, Lakshmanane; Sette, Alessandro; Antunes, Ricardo da Silva

doi:10.1101/2022.03.01.482548

Cited by 5 publications

(5 citation statements)

References 58 publications

(113 reference statements)

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“…Our results are consistent with previous studies demonstrating the lack of SARS-CoV-2 neutralizing activity in pre-pandemic sera (46) and the absence of correlation with protection and severity of COVID-19 (45). Nevertheless, other studies support the hypothesis that previous hCoV exposure may influence (positively or negatively) the outcome of COVID-19 (47)(48)(49)(50).…”

Section: Discussionsupporting

confidence: 93%

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Denis¹,

Garnier²,

Cheutin³

et al. 2023

Front. Immunol.

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IntroductionCurrent approved COVID-19 vaccines, notably mRNA and adenoviral vectored technologies, still fail to fully protect against infection and transmission of various SARS-CoV-2 variants. The mucosal immunity at the upper respiratory tract represents the first line of defense against respiratory viruses such as SARS-CoV-2 and is thus critical to develop vaccine blocking human-to-human transmission.MethodsWe measured systemic and mucosal Immunoglobulin A (IgA) response in serum and saliva from 133 healthcare workers from Percy teaching military hospital following a mild infection (SARS-CoV-2 Wuhan strain, n=58) or not infected (n=75), and after SARS-CoV-2 vaccination (Vaxzevria®/Astrazeneca and/or Comirnaty®/Pfizer).ResultsWhile serum anti-SARS-CoV-2 Spike IgA response lasted up to 16 months post-infection, IgA response in saliva had mostly fallen to baseline level at 6 months post-infection. Vaccination could reactivate the mucosal response generated by prior infection, but failed to induce a significant mucosal IgA response by itself. Early post-COVID-19 serum anti-Spike-NTD IgA titer correlated with seroneutralization titers. Interestingly, its saliva counterpart positively correlated with persistent smell and taste disorders more than one year after mild COVID-19.DiscussionAs breakthrough infections have been correlated with IgA levels, other vaccine platforms inducing a better mucosal immunity are needed to control COVID-19 infection in the future. Our results encourage further studies to explore the prognosis potential of anti-Spike-NTD IgA in saliva at predicting persistent smell and taste disorders.

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Section: Discussionsupporting

confidence: 93%

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Denis¹,

Garnier²,

Cheutin³

et al. 2023

Front. Immunol.

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“…We also found FluoroSpot responses in uninfected unvaccinated participants to Sp6 that spans part of the S2 subunit. Longitudinal studies suggest that HCoVs induce a stable pool of memory CD4+ T cells that may account for the FluoroSpot IFN-γ responses in participants with no prior COVID-19 infection [ 63 ]. Cross-reactive epitopes present in SARS-CoV-2 and other HCoVs have been identified in the S, N and M proteins [ 46 , 61 , 64 – 66 ], including within the Sp6 and Mp1 subpools.…”

Section: Discussionmentioning

confidence: 99%

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection

Porter¹,

Goguet²,

Ganeshan³

et al. 2022

PLoS ONE

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Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination (‘hybrid immunity’) further augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/106 cytokine-producing peripheral blood mononuclear cells [PBMCs]). Almost all vaccinated participants with no prior infection exhibited IFN-γ, IL-2 and IFN-γ+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-γ, IL-2 and IFN-γ+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-γ but not IL2 or IFN-γ+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-γ, IL-2, and IFN-γ+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.

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“…OC43 and NL63 RBD ELISA were carried out as previously described 80,81 . Briefly, coating was performed by Streptavidin (Invitrogen) at 4 μg/mL in Tris-Buffered Saline (TBS) pH 7.4 for 1 h at 37°C followed by blocking with Non-Animal Protein-BLOCKER ™ (GBiosciences).…”

Section: Methods Detailsmentioning

confidence: 99%

Targets and cross-reactivity of human T cell recognition of Common Cold Coronaviruses

Tarke

Zhang

Methot

et al. 2023

Preprint

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The Coronavirus (CoV) family includes a variety of viruses able to infect humans. Endemic CoVs that can cause common cold belong to the alphaCoV and betaCoV genera, with the betaCoV genus also containing subgenera with zoonotic and pandemic concern, including sarbecoCoV (SARS-CoV and SARS-CoV-2) and merbecoCoV (MERS-CoV). It is therefore warranted to explore pan-CoV vaccine concepts, to provide adaptive immune protection against new potential CoV outbreaks, particularly in the context of betaCoV sub lineages. To explore the feasibility of eliciting CD4+ T cell responses widely cross-recognizing different CoVs, we utilized samples collected pre-pandemic to systematically analyze T cell reactivity against representative alpha (NL63) and beta (OC43) common cold CoVs (CCC). Similar to previous findings on SARS-CoV-2, the S, N, M, and nsp3 antigens were immunodominant for both viruses while nsp2 and nsp12 were immunodominant for NL63 and OC43, respectively. We next performed a comprehensive T cell epitope screen, identifying 78 OC43 and 87 NL63-specific epitopes. For a selected subset of 18 epitopes, we experimentally assessed the T cell capability to cross-recognize sequences from representative viruses belonging to alphaCoV, sarbecoCoV, and beta-non-sarbecoCoV groups. We found general conservation within the alpha and beta groups, with cross-reactivity experimentally detected in 89% of the instances associated with sequence conservation of >67%. However, despite sequence conservation, limited cross-reactivity was observed in the case of sarbecoCoV (50% of instances), indicating that previous CoV exposure to viruses phylogenetically closer to this subgenera is a contributing factor in determining cross-reactivity. Overall, these results provided critical insights in the development of future pan-CoV vaccines.

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Immunological memory to Common Cold Coronaviruses assessed longitudinally over a three-year period

Cited by 5 publications

References 58 publications

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Long-term systemic and mucosal SARS-CoV-2 IgA response and its association with persistent smell and taste disorders

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection

Targets and cross-reactivity of human T cell recognition of Common Cold Coronaviruses

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