Immunological memory to common cold coronaviruses assessed longitudinally over a three-year period pre-COVID19 pandemic

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

doi:10.1016/j.chom.2022.07.012

Cited by 26 publications

(21 citation statements)

References 61 publications

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“…By simultaneously identifying SARS-CoV-2-reactive and OC43-specific T cell responses to the structural proteins S, M, and N, we demonstrated a close relationship between the mCD4 + T cell populations. In adults, our data confirmed that the OC43-specific and SARS-CoV-2-reactive T cell responses remain stable over time ( 32 ). While most adults had responses against OC43 S and N, the cross-reactive responses more frequently targeted the S rather than the N region, as displayed at both protein and epitope levels.…”

Section: Discussionsupporting

confidence: 77%

Functional SARS-CoV-2 cross-reactive CD4 ⁺ T cells established in early childhood decline with age

Humbert

Olofsson

Wullimann

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Pre-existing SARS-CoV-2-reactive T cells have been identified in SARS-CoV-2-unexposed individuals, potentially modulating COVID-19 and vaccination outcomes. Here, we provide evidence that functional cross-reactive memory CD4 + T cell immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is established in early childhood, mirroring early seroconversion with seasonal human coronavirus OC43. Humoral and cellular immune responses against OC43 and SARS-CoV-2 were assessed in SARS-CoV-2-unexposed children (paired samples at age two and six) and adults (age 26 to 83). Pre-existing SARS-CoV-2-reactive CD4 + T cell responses targeting spike, nucleocapsid, and membrane were closely linked to the frequency of OC43-specific memory CD4 + T cells in childhood. The functional quality of the cross-reactive memory CD4 + T cell responses targeting SARS-CoV-2 spike, but not nucleocapsid, paralleled OC43-specific T cell responses. OC43-specific antibodies were prevalent already at age two. However, they did not increase further with age, contrasting with the antibody magnitudes against HKU1 (β-coronavirus), 229E and NL63 (α-coronaviruses), rhinovirus, Epstein–Barr virus (EBV), and influenza virus, which increased after age two. The quality of the memory CD4 + T cell responses peaked at age six and subsequently declined with age, with diminished expression of interferon (IFN)-γ, interleukin (IL)-2, tumor necrosis factor (TNF), and CD38 in late adulthood. Age-dependent qualitative differences in the pre-existing SARS-CoV-2-reactive T cell responses may reflect the ability of the host to control coronavirus infections and respond to vaccination.

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Section: Discussionsupporting

confidence: 77%

Functional SARS-CoV-2 cross-reactive CD4 ⁺ T cells established in early childhood decline with age

Humbert

Olofsson

Wullimann

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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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 – 50 ).…”

Section: Discussionmentioning

confidence: 84%

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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“…Conversely, Naranbhai and colleagues found that the T cell response against the spike protein was low in 10 non-vaccinated and never-infected subjects, although effector T cell reactivity to the Omicron spike protein was higher than to the Wuhan Hu-1 spike protein (55), as in our experimental setting. A recent study suggested the existence of a unique insertion mutation in the Omicron spike protein that has a sequence that is identical to that of a coronavirus that causes the common cold (65), which may explain why T cells developed against common cold coronaviruses can cross-react with the SARS-CoV-2 spike protein (66)(67)(68)(69)(70)(71)(72)(73). In light of these data and our present findingof increased B and T cross-reactivity against Omicron in pre-pandemic samples from healthy donorsit is tempting to speculate that Omicron is acquiring mutations in the spike protein that are reminiscent, at least in part, of common cold coronaviruses, possibly explaining its increased infectivity but lower intrinsic virulence (74).…”

Section: Resultsmentioning

confidence: 99%

Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose

Perico

Todeschini²,

Casiraghi³

et al. 2023

Front. Immunol.

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We examined the immune response in subjects previously infected with SARS-CoV2 and infection-naïve 9 months after primary 2-dose COVID-19 mRNA vaccination and 3 months after the booster dose in a longitudinal cohort of healthcare workers. Nine months after primary vaccination, previously infected subjects exhibited higher residual antibody levels, with significant neutralizing activity against distinct variants compared to infection-naïve subjects. The higher humoral response was associated with higher levels of receptor binding domain (RBD)-specific IgG+ and IgA+ memory B cells. The booster dose increased neither neutralizing activity, nor the B and T cell frequencies. Conversely, infection-naïve subjects needed the booster to achieve comparable levels of neutralizing antibodies as those found in previously infected subjects after primary vaccination. The neutralizing titer correlated with anti-RBD IFNγ producing T cells, in the face of sustained B cell response. Notably, pre-pandemic samples showed high Omicron cross-reactivity. These data show the importance of the booster dose in reinforcing immunological memory and increasing circulating antibodies in infection-naïve subjects.

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Immunological memory to common cold coronaviruses assessed longitudinally over a three-year period pre-COVID19 pandemic

Cited by 26 publications

References 61 publications

Functional SARS-CoV-2 cross-reactive CD4 ⁺ T cells established in early childhood decline with age

Functional SARS-CoV-2 cross-reactive CD4 ⁺ T cells established in early childhood decline with age

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

Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose

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Immunological memory to common cold coronaviruses assessed longitudinally over a three-year period pre-COVID19 pandemic

Cited by 26 publications

References 61 publications

Functional SARS-CoV-2 cross-reactive CD4 + T cells established in early childhood decline with age

Functional SARS-CoV-2 cross-reactive CD4 + T cells established in early childhood decline with age

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

Long-term adaptive response in COVID-19 vaccine recipients and the effect of a booster dose

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Functional SARS-CoV-2 cross-reactive CD4 ⁺ T cells established in early childhood decline with age

Functional SARS-CoV-2 cross-reactive CD4 ⁺ T cells established in early childhood decline with age