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Targets and cross-reactivity of human T cell recognition of common cold coronaviruses.

ABSTRACT: The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and Beta (OC43) common cold CoVs (CCCs) in pre-pandemic samples. S, N, M, and nsp3 antigens are immunodominant, as shown for severe acute respiratory syndrome 2 (SARS2), while nsp2 and nsp12 are Alpha or Beta specific. We further identify 78 OC43- and 87 NL63-specific epitopes, and, for a subset of those, we assess the T cell capability to cross-recognize sequences from representative viruses belonging to AlphaCoV, sarbecoCoV, and Beta-non-sarbecoCoV groups. We find T cell cross-reactivity within the Alpha and Beta groups, in 89% of the instances associated with sequence conservation >67%. However, despite conservation, limited cross-reactivity is observed for sarbecoCoV, indicating that previous CoV exposure is a contributing factor in determining cross-reactivity. Overall, these results provide critical insights in developing future pan-CoV vaccines.

SUBMITTER: Tarke A

PROVIDER: S-EPMC10242702 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Targets and cross-reactivity of human T cell recognition of common cold coronaviruses.

Tarke Alison A Zhang Yun Y Methot Nils N Narowski Tara M TM Phillips Elizabeth E Mallal Simon S Frazier April A Filaci Gilberto G Weiskopf Daniela D Dan Jennifer M JM Premkumar Lakshmanane L Scheuermann Richard H RH Sette Alessandro A Grifoni Alba A

Cell reports. Medicine 20230529 6

The coronavirus (CoV) family includes several viruses infecting humans, highlighting the importance of exploring pan-CoV vaccine strategies to provide broad adaptive immune protection. We analyze T cell reactivity against representative Alpha (NL63) and Beta (OC43) common cold CoVs (CCCs) in pre-pandemic samples. S, N, M, and nsp3 antigens are immunodominant, as shown for severe acute respiratory syndrome 2 (SARS2), while nsp2 and nsp12 are Alpha or Beta specific. We further identify 78 OC43- an ...[more]

PMID: 37295422

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Project description:IntroductionThe nonstructural protein 12 (NSP12) of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has a high sequence identity with common cold coronaviruses (CCC).MethodsHere, we comprehensively assessed the breadth and specificity of the NSP12-specific T-cell response after in vitro T-cell expansion with 185 overlapping 15-mer peptides covering the entire SARS-CoV-2 NSP12 at single-peptide resolution in a cohort of 27 coronavirus disease 2019 (COVID-19) patients. Samples of nine uninfected seronegative individuals, as well as five pre-pandemic controls, were also examined to assess potential cross-reactivity with CCCs.ResultsSurprisingly, there was a comparable breadth of individual NSP12 peptide-specific CD4+ T-cell responses between COVID-19 patients (mean: 12.82 responses; range: 0-25) and seronegative controls including pre-pandemic samples (mean: 12.71 responses; range: 0-21). However, the NSP12-specific T-cell responses detected in acute COVID-19 patients were on average of a higher magnitude. The most frequently detected CD4+ T-cell peptide specificities in COVID-19 patients were aa236-250 (37%) and aa246-260 (44%), whereas the peptide specificities aa686-700 (50%) and aa741-755 (36%), were the most frequently detected in seronegative controls. In CCC-specific peptide-expanded T-cell cultures of seronegative individuals, the corresponding SARS-CoV-2 NSP12 peptide specificities also elicited responses in vitro. However, the NSP12 peptide-specific CD4+ T-cell response repertoire only partially overlapped in patients analyzed longitudinally before and after a SARS-CoV-2 infection.DiscussionThe results of the current study indicate the presence of pre-primed, cross-reactive CCC-specific T-cell responses targeting conserved regions of SARS-CoV-2, but they also underline the complexity of the analysis and the limited understanding of the role of the SARS-CoV-2 specific T-cell response and cross-reactivity with the CCCs.

Project description:The common cold coronaviruses are a source of ongoing morbidity and mortality particularly among elderly and immunocompromised individuals. While cross-reactive immune responses against multiple coronaviruses have been described following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination, it remains unclear if these confer any degree of cross-protection against the common cold coronaviruses. A recombinant fowl adenovirus vaccine expressing the SARS-CoV-2 spike protein (FAdV-9-S19) was generated, and protection from SARS-CoV-2 challenge was shown in K18-hACE2 mice. Vaccinated mice were also challenged with the common cold coronaviruses human coronavirus (HCoV)-OC43 and HCoV-NL63 by the intranasal route, and viral shedding and lung burden were reduced in these groups compared to unvaccinated animals. Histopathological analysis of lung tissues revealed significantly less inflammation and lower pathology scores in mice that received FAdV-9-S19 . Because no mouse model for the coronavirus HCoV-229E exists, we vaccinated and challenged cynomolgus macaques to evaluate cross-protection against HCoV-229E. Animals were monitored for clinical signs of disease and viral shedding. Infectious virus was detected in both groups throughout the course of infection; however, vaccinated animals showed reduced viral shedding at multiple time points after infection. Histopathological analysis of lung tissues following challenge also indicated a more moderate disease in the vaccinated animals. Therefore, vaccination with FAdV-9-S19 also provided a moderate cross-protection against HCoV-229E disease in the cynomolgus macaques infection model. Our study demonstrates that vaccination with a recombinant fowl adenovirus expressing SARS-CoV-2 spike protein can provide a low-level cross-protection against beta- and alphacoronaviruses. These findings are important for the design of future pan-coronavirus vaccines.IMPORTANCEThe common cold coronaviruses are a source of ongoing morbidity and mortality particularly among elderly and immunocompromised individuals, and no vaccine is currently available. Cross-reactive immune responses have been described following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination; however, it remains unclear what degree of cross-protection they confer against the common cold coronaviruses. We demonstrate that both humoral and cell-mediated immune responses provide a low-level cross-protection, resulting in reduced viral load and pathology for the common cold coronaviruses OC43 and NL63 in mouse models. Additionally, we present a novel non-human primate (NHP) model of infection with the common cold coronavirus 229E, demonstrating that it mimics the disease observed in humans and can serve as a model for future vaccine studies, as cross-protection was also observed. This is significant as it suggests that current vaccines could provide a low-level protection against other coronaviruses and could serve as part of vaccination strategy against future novel coronaviruses.

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Targets and cross-reactivity of human T cell recognition of common cold coronaviruses.

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Targets and cross-reactivity of human T cell recognition of common cold coronaviruses.

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