Cross-Reactive Immune Responses toward the Common Cold Human Coronaviruses and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): Mini-Review and a Murine Study

Abstract

While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes serious morbidity and mortality in humans (coronavirus disease 2019, COVID-19), there is an enormous range of disease outcomes following virus exposures. Some individuals are asymptomatic while others succumb to virus infection within days. Presently, the factors responsible for disease severity are not fully understood. One factor that may influence virus control is pre-existing immunity conferred by an individual’s past exposures to common cold human coronaviruses (HCoVs). Here, we describe previous literature and a new, murine study designed to examine cross-reactive immune responses between SARS-CoV-2 and common cold HCoVs (represented by prototypes OC43, HKU1, 229E, and NL63). Experimental results have been mixed. In SARS-CoV-2-unexposed humans, cross-reactive serum antibodies were identified toward nucleocapsid (N) and the spike subunit S2. S2-specific antibodies were in some cases associated with neutralization. SARS-CoV-2-unexposed humans rarely exhibited antibody responses to the SARS-CoV-2 spike subunit S1, and when naïve mice were immunized with adjuvanted S1 from either SARS-CoV-2 or common cold HCoVs, S1-specific antibodies were poorly cross-reactive. When humans were naturally infected with SARS-CoV-2, cross-reactive antibodies that recognized common cold HCoV antigens increased in magnitude. Cross-reactive T cells, like antibodies, were present in humans prior to SARS-CoV-2 exposures and increased following SARS-CoV-2 infections. Some studies suggested that human infections with common cold HCoVs afforded protection against disease caused by subsequent exposures to SARS-CoV-2. Small animal models are now available for the testing of controlled SARS-CoV-2 infections. Additionally, in the United Kingdom, a program of SARS-CoV-2 human challenge experiments has received regulatory approval. Future, controlled experimental challenge studies may better define how pre-existing, cross-reactive immune responses influence SARS-CoV-2 infection outcomes.

Microarray-Based Detection of Antibodies against SARS-CoV-2 Proteins, Common Respiratory Viruses and Type I Interferons

“…For antibodies against viruses, cross-species interactions can have an influence. Cross-reactivity of immune responses between SARS-CoV-2 and seasonal coronavirus has recently been reported [6,43,44]. As shown by Tso et al, the SARS-CoV-2 nucleocapsid is the major antigen recognized by these cross-reactive antibodies [45].…”

“…Although seasonal HCoVs are responsible for up to 15-30% of common colds in adults, there are insufficient data on the epidemiology of these four viruses worldwide [4]. Cross reactions between preexisting antibodies against proteins of common seasonal coronaviruses and those of the new SARS-CoV-2 have been studied by several research groups [5][6][7]. However, whether crossreactive antibodies against seasonal coronaviruses protect against COVID-19 requires further study [8].…”

Microarray-based detection of antibodies against SARS-CoV-2 proteins, common respiratory viruses and type I interferons

“…For antibodies against viruses, cross-species interactions can have an influence. Cross-reactivity of immune responses between SARS-CoV-2 and seasonal coronavirus has recently been reported [26][27][28]. As shown by Tso et al, the SARS-CoV-2 nucleocapsid is the major antigen recognized by these cross-reactive antibodies [29].…”

Distinct Antibody Responses to Endemic Coronaviruses Pre- and Post-SARS-CoV-2 Infection in Kenyan Infants and Mothers

“…Pre-existing immune cross-protection and a lower median age have been hypothesized as correlates of protection against severe COVID-19 in sub-Saharan Africa [ 30 , 31 ]. However, whether pre-existing eHCoV antibodies are protective or increase the risk of SARS-CoV-2 infection remains controversial [ 32 ], and this relationship is particularly understudied in infants. In our study, prior eHCoV antibody titers were not strongly associated with SARS-CoV-2 seroconversion.…”