"Immunological imprinting" could influence antibody response to COVID-19

Researchers in the United States and Spain have shown that prior exposure to seasonal coronaviruses may influence antibody responses to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the causative agent of coronavirus disease 2019 (COVID-19).

Longitudinal profiling of the humoral response to SARS-CoV-2 among hospitalized patients suggested that this "immunological imprinting" due to previous infection with seasonal human betacoronaviruses may determine antibody profiles in cases of COVID-19.

The team from the Icahn School of Medicine at Mount Sinai in New York; the University of Barcelona, and the Carlos III Health Institute in Madrid said:

"Our observation has important implications for the development of COVID-19 vaccines, and the potential interactions with pre-existing immunity should be taken into consideration in the path to an effective vaccine, to ultimately control the ongoing pandemic."

A pre-print version of the paper is available in the server medRxiv*, while the article undergoes peer review.

Humans are susceptible to six coronaviruses other than SARS-CoV-2

SARS-CoV-2 belongs to a large family of viruses - called Coronavirinae - that infect both mammals and birds. Humans are susceptible to six other coronaviruses, all of which typically cause respiratory illness, although to different degrees of severity.

SARS-CoV-1 and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), for example, are highly pathogenic coronaviruses that have caused dangerous outbreaks in humans over the last two decades. The seasonal coronaviruses OC43, HKU1, 223E, and NL63, on the other hand, usually only cause mild to moderate upper respiratory disease.

The role of viral membrane proteins

Previous studies have demonstrated that one main target of antibody responses to infection with coronaviruses is a structure on the viral membrane called the spike protein, which mediates binding and fusion to the human host cell receptor ACE2. Furthermore, antibodies targeting the receptor-binding domain (RBD) of this spike protein have been shown to neutralize the virus.

The antibodies against the spike RBD are highly specific and do not generally exhibit cross-reactivity between the different seasonal coronaviruses.

However, a more cross-reactive structure on the viral surface called nucleoprotein (NP) has been shown to induce antibodies in COVID-19 patients, although antibodies against NP do not neutralize SARS-CoV-2 in tissue culture.

Although some studies have demonstrated cell-mediated and serum cross-reactivity between epitopes from SARS-CoV-2 and seasonal human coronaviruses, it remains unclear whether previous exposure to these other coronaviruses influences the immune response following exposure to a novel but closely related antigen.

Exploring the effects of immunological imprinting

This phenomenon, referred to as "immunological imprinting," triggers the immune system to recall pre-existing memory responses rather than inducing de novo responses.

"This has been well studied for viruses like influenza and is a fundamental piece to inform vaccine development," says Adolfo Garcia-Sastre (Icahn School of Medicine at Mount Sinai) and colleagues.

To explore whether immunological imprinting may influence the immune response to COVID-19, the team profiled the early humoral immune response against SARS-CoV-2 among a longitudinal cohort of hospitalized COVID-19 patients and also quantified levels of antibodies against the seasonal coronaviruses OC43, HKU1, and 223E.

The patients (mean age 65 years) were recruited at the University Hospital of Bellvitge during the first wave of SARS-CoV-2 in Barcelona from March 26th to May 28th, 2020.

All patients a strong back-boosting of antibodies against OC43 and HKU1

All patients developed detectable levels of antibodies against SARS-CoV-2 spike and NP, with levels peaking seven days following recruitment.

Patients exhibited a strong back-boosting of antibodies against conserved epitopes of the OC43 and HKU1 spike proteins, but not against the variable regions of these viruses or 223E.  

However, simple linear regression analysis identified a negative correlation between antibody memory boost to human coronaviruses and the induction of the antibodies immunoglobulin G (IgG) and IgM against the spike protein of SARS-CoV-2.

"Our findings provide a dynamic characterization of the antibody response against SARS-CoV-2 in COVID-19 patients and provide evidence of immune imprinting in these patients," writes Garcia-Sastre and colleagues.

What are the implications of the study?

The researchers say the findings show that the antibody response against SARS-CoV-2 infection and, potentially vaccination, may be influenced by imprinting of the B cell compartment as a result of previous exposure to seasonal human coronaviruses.

"It will be important to investigate the potential functional consequences of this imprinting in the induction of protective immune responses after SARS-CoV-2 infection and vaccination in the long term," concludes the team.

*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:
Sally Robertson

Written by

Sally Robertson

Sally has a Bachelor's Degree in Biomedical Sciences (B.Sc.). She is a specialist in reviewing and summarising the latest findings across all areas of medicine covered in major, high-impact, world-leading international medical journals, international press conferences and bulletins from governmental agencies and regulatory bodies. At News-Medical, Sally generates daily news features, life science articles and interview coverage.


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  1. Frank P Mora Frank P Mora United States says:

    Of the alpha coronaviruses mentioned, only NL63 binds to ACE2.

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