Researchers explore adaptive immunity against human coronaviruses

A recent study, currently available on medRxiv* preprint server, shows that long-term adaptive immunity to endemic coronaviruses is widespread, but low in magnitude, and that it shares phenotypic features of spike-specific antibodies and T cell memory across all tested coronaviruses.

Study: Adaptive immunity to human coronaviruses is widespread but low in magnitude. Image Credit: Kateryna Kon / Shutterstock
Study: Adaptive immunity to human coronaviruses is widespread but low in magnitude. Image Credit: Kateryna Kon / Shutterstock

Unlike the highly pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the a causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, alongside original SARS-CoV and MERS-CoV, endemic human coronaviruses circulate widely around the world, but typically cause common cold with rather limited morbidity and mortality.

However, despite the early development of immunity against multiple endemic human coronaviruses, a majority of adults are still susceptible to periodic re-infections – most notably those that are immunocompromised. As the infection is mild or even asymptomatic, partially protective immune memory can be considered.

When COVID-19 pandemic is concerned, defining the degree of serological and cellular immunity needed to protect against reinfection or severe disease remains a fundamental question. It is likely that a mixture of serum antibodies and T/B memory cells provides a long-term protection.

Consequently, the study of coronavirus-specific T and B cell memory can give us a crucial preview into the development of long-lasting, protective SARS-CoV-2 immunity, as the role of cross-reactive immunity, and which cells dominate in the response, is currently unclear.

Hence, to address important knowledge gaps regarding this issue, a research group led by the Dr. Hyon-Xhi Tan from the University of Melbourne, Australia, aimed to assess the prevalence and phenotypic characteristics of spike-specific antibodies against human coronaviruses, as well as memory T and B cell responses in a cohort of SARS-CoV-2 uninfected adults.

Methodological approach

For the purposes of this study, researchers have recruited a cohort of 42 SARS-CoV-2 uninfected adults from 18 to 67 years of age, without any recent cold symptoms or other signs related to COVID-19. In this group of individuals, the researchers have quantified CD4 T-cell and antibody responses to spike antigens.

More specifically, to determine the distribution of CD4 T cell memory responses, they have stimulated peripheral blood mononuclear cells with recombinant spike glycoprotein antigens and quantified antigen-specific T memory cells by measuring up-regulation of the activation markers CD25 and OX-40 by flow cytometry.

Taking into account the divergent host receptor specificity and potential differences in tissue tropism among human coronaviruses, the researchers have also appraised whether memory or chemokine receptor phenotypes differed among spike-specific CD4 T-cell populations. Tissue samples from human donors were used for this scientific endeavor.

Cellular vs. humoral immunological memory

In a nutshell, this study has revealed that the magnitude of immunity to human coronaviruses is independent of age and characterized by quite robust antibody titers, widespread CD4 T cell memory within both T memory cells and circulating T follicular helper cells, as well as by an enrichment of T cell memory in lung-draining lymph nodes.

SARS-CoV-2 cross-reactive T cells have been observed in 48 percent of study participants, and correlated with specific human coronavirus HKU1 memory. Furthermore, human coronavirus-specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for CXCR3 expression and frequency in human lung draining lymph nodes.

On the other hand, neutralizing antibody activity was relatively low, and memory B cells were only sporadically detected in the circulation or lung-draining lymph nodes. Cellular and humoral immunological memory seems to be independently maintained for human coronaviruses.

A preview of a long-term immunity

Overall, these data clarify the characteristics of long-term immunity to endemic coronaviruses, which have comparable magnitudes and share phenotypic features of spike-specific antibody and T cell memory across all four human coronaviruses," say study authors.

As the modest neutralization activity shows that sterilizing humoral cross-immunity is likely absent, there is an emphasis on additive contributions of multiple arms of adaptive immune system – specifically anti-viral T-cell responses.

These types of insights into the homeostatic maintenance of immunity against human coronaviruses are likely to provide a preview of a long-term specific immunity established either after wide-spread infection or vaccination.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.

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