Scientists explore immune memory of common cold coronaviruses before the SARS-CoV-2 pandemic era

By Shanet Susan AlexJul 26 2022Reviewed by Aimee Molineux

In a recent study published in the Cell Host and Microbe journal, researchers assessed the immune memory of common cold coronaviruses (CCCs) three years before the coronavirus disease 2019 (COVID-19) pandemic.

Background

CCCs are seasonal viruses that fall into two genera: alpha-coronaviruses (CoVs), which include HCoV-NL63 and HCoV-229E, and beta-CoVs, which include HCoVHKU1 and HCoV-OC43, that most usually cause mild diseases in humans.

CCCs are endemic viruses with extensive worldwide distribution and have been circulating for a while among humans. The severe acute respiratory syndrome Coronavirus (SARS-CoV), severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), and the Middle East respiratory syndrome CoV (MERS-CoV) are all CoVs that cause severe illness in humans and are associated phylogenetically with the CCC viruses.

Nevertheless, there is inadequate evidence on the prevalence of memory T cell reaction toward CCC, especially their stability with time. Comprehending the steady-state dynamics of CCC antibody and T cell reactions in people has potential significance, given the sustained SARS-CoV-2 evolution during the COVID-19 pandemic. 

Additionally, CCC immunological memory impacts the outcome of the SARS-CoV-2 infection, and developing a pan-CoV vaccine requires an understanding of this impact.

About the study

In the current work, the researchers examined CD4+ T cell and antibody responses to CCC, other respiratory viruses, and ubiquitous or chronic pathogens throughout a longitudinal analysis spanning six months to three years in pre-COVID-19-pandemic samples of young adults from 2016 to 2019. They characterized CD4+ T cell-selective memory reflexes to the four prototypic widely and endemically circulating CCC viruses, namely 229E, NL63, OC43, and HKU1, across a longitudinal population. As a method, the investigators used ex vivo treatment of peripheral blood mononuclear cells (PBMCs) with peptide libraries that span the whole proteome of each virus.

The team analyzed PBMC samples of 32 subjects from an observational study of Bordetella pertussis. They examined the magnitudes of CD4+ T cell reactions to CCC and other antigens over time. Moreover, immunoglobulin (Ig) binding to recombinant spike (S) receptor-binding domain (RBD) antigens of CCC were examined in matched plasma samples.

Results

The researchers found that about 72% to 81% of participants showed modest immune CD4+ T cell memory reactions to each of the four CCC under investigation, with magnitudes and frequencies coherent with earlier values observed in both cohorts of community and healthcare workers. These values were also comparable to two prior research findings. In addition, these immune reactions harbored a modest level of SARS-CoV-2 cross-reactivity. Interestingly, the CCC-specific response magnitude was similar to the immunodominant and ubiquitous pathogen cytomegalovirus (CMV).

The scientists discovered a consistent and long-lasting T cell and antibody reaction against CCC, corroborated by various recent experimental results. The current findings were also consistent with the longevity of immune reactions to other viral infections, such as SARS-CoV-1 or vaccinia, where antigen-selective cells were found 17 and 50 years after infection, respectively, and with torque teno virus (TTV), which is exceptionally stable for many years after vaccination.

While everyone showed measurable antibody titers to CCC, the team discovered that individuals' levels of T cell reactivity varied. Further, the participants most likely to be linked to pre-existing SARS-CoV-2 immunological reactivity were those with significant CCC T cell reactivity and low antibody titers.

The present data also imply that some people, and not all, bear pre-existing T cell memory reactivity to SARS-CoV-2 due to the level of sequence homology between SARS-CoV-2 and CCC. Besides, the authors suggested that additional factors, including recent exposure, human leukocyte antigen (HLA) kind, or other individualized and environmental factors, could be at play.

Conclusions

The study data showed how a significant and long-lasting immunity to CoVs was maintained in the young adult population throughout time, most likely of repeated prior exposures and maybe sporadic reinfections. The researchers stated that further protection might come from establishing pan-coronavirus vaccines that address SARS-CoV-2 and CCC viruses.

Notably, the study discovered that CCC immune reactions were frequently seen as comparable to those of other common antigens and were long-lasting. Low HLA-DR+CD38+ signals were linked to CCC-specific CD4+ T cell responses, and the size of these responses was not associated with the frequency of CCC infections each year.

Likewise, CCC-specific S RBD-specific IgG reactions remained constant throughout time. Finally, pre-existing SARS-CoV-2 immunity was linked to significant CCC-specific CD4+ T cell reactivity, not antibody titers. 

The authors noted that even if at least a few reinfections might have happened throughout the longitudinal follow-up period, the overwhelming body of data implies that the identified reactivity was linked to memory and lasting reactions.