Adaptive immunity to human coronaviruses is widespread but low in magnitude.

Hyon‐Xhi Tan,Helen Opdam,Wen Shi Lee,Angela Vago,Thakshila Amarasena,Graham Starkey,Jennifer A Juno,Osamu Yoshino,Thomas Tiang,Robyn Esterbauer,Christina Nelson,Kathleen Wragg ,Hannah G Kelly ,Claire L Gordon ,Laura K Mackay ,M L Grayson ,Robert Balakas ,Casey Asmus ,Rohit D’costa ,Stephen J Kent ,Adam K Wheatley ,Greg Przybylowski ,Bao‐Zhong Wang ,Rod Moore ,Robert M Jones ,D H Pritchard ,Rene C Batac

doi:10.1002/cti2.1264

Abstract

ObjectivesEndemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV‐specific T‐cell memory in adults.MethodsWe quantified CD4 T‐cell and antibody responses to hCoV spike antigens in 42 SARS‐CoV‐2‐uninfected individuals. Antigen‐specific memory T cells and circulating T follicular helper (cTFH) cells were identified using an activation‐induced marker assay and characterised for memory phenotype and chemokine receptor expression.ResultsT‐cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS‐CoV‐2 cross‐reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV‐specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung‐draining lymph nodes.ConclusionOverall, hCoV‐specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus‐specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS‐CoV‐2.

Highlights

In contrast to the high pathogenicity of MERS-CoV, SARS-CoV and SARS-CoV-2 coronaviruses, endemic human coronaviruses circulate worldwide but typically cause common colds with only limited morbidity and mortality[1]
Results human coronaviruses (hCoV)-specific antibody and CD4 T cell memory is common among adults
In addition to near-universal plasma antibody reactivity to hCoV, memory T cell responses to both a- and bCoV are widespread

Summary

Introduction

In contrast to the high pathogenicity of MERS-CoV, SARS-CoV and SARS-CoV-2 coronaviruses, endemic human coronaviruses (hCoV) circulate worldwide but typically cause common colds with only limited morbidity and mortality[1]. Despite the early development of immunity against multiple hCoV, most adults remain susceptible to periodic reinfection[6,7,8], with increased susceptibility among immunocompromised individuals[9,10,11]. This suggests the magnitude and/or quality of hCoV-targeted immunity in adults is insufficient for sterilizing protection but instead may limit the burden of disease to asymptomatic or mild infection[8]. The study of hCoV-specific T and B cell memory can provide a key preview into the development of durable, protective SARS-CoV-2 immunity

Methods

Results

Conclusion