Scientists investigate antigen imprinting of SARS-CoV-2

Whenever a variant of a pathogen (for example, a virus or bacterium) is encountered, the body’s immune system’s tendency to selectively use immunological memory based on past infections is called “antigen imprinting.”

Group 1 influenza A viruses are H1N1 and H2N2, and Group 2 influenza A viruses are H3N2. Previously, differences in vulnerabilities to other potentially deadly influenza viruses, such as H5N1 and H7N9, were associated with an individual’s first viral subtype exposure to influenza A virus at a young age.

This type of imprint can have long-term imprints antigen-Specific protection. This can be favorable, neutral, or negative. Knowledge of this phenomenon may help evaluate and strategize better vaccination protocols for specific targets.

Background

With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019, a global pandemic continues.Previous seasonal coronavirus infections are now known to inhibit the development of immunoglobulin G (IgG) and IgM against SARS-CoV-2, suggesting immunological imprints from other betas. coronavirus.. Nevertheless, the potential extent, effects, and processes of antigen imprinting in exposure to multiple SARS-CoV-2 mutants are just beginning to be revealed.

The Omicron strain is a rapidly prevalent and immune avoidant concern (VOC) for SARS-CoV-2. This mutant may break the protective immunity provided by the COVID-19 vaccine and avoid most monoclonal antibody (mAb) treatments.

In a previous study, three doses of the ancestral messenger ribonucleic acid (mRNA) vaccine conferred neutralizing titers on the Omicron mutant, comparable to levels effective for delta neutralization after two mRNA vaccinations. It has been shown to be done.

Notably, the advent of Omicron initially prompted the development of mRNA vaccines based on the Omicron sequence to promote additional benefits when administered as a booster or first-line vaccine. However, no significant difference was observed in Makaku’s study comparing booster doses to ancestral wild-type mRNA vaccines targeting omicron or beta mRNA vaccines in terms of neutralization. titer Or disease protection.

In the first human trial using a beta-based or delta-based mRNA booster vaccine, multiple variant booster doses elicited comparable neutralization titers.

On the other hand, non-immune individuals infected with either the alpha or delta mutant had antibodies that showed preferential binding to the receptor binding domain (RBD) of the corresponding strain. Individuals who were immunized against the ancestral strain and experienced a breakthrough in the alpha or delta strain showed the same RBD binding pattern as the non-immunized individuals in the convalescent phase in the ancestral strain alone.

Research and findings

Recently published research Clinical and translational medicine Monoclonal RBD antibody responses induced by SARS-CoV-2 beta mutant infection were compared to antibodies induced by ancestral virus in immunologically naive subjects. Most beta-induced mAbs isolated from memory B cells did not bind to ancestral strains, whereas other mAbs were observed to strongly neutralize beta, ancestral strains, and other VOCs. Therefore, immunization with antigenically distant SARS-CoV-2 mutants induces variant-specific memory B cells that establish clear imprints that memory B cells can use for subsequent recall with the same or variant antigens. There is likely to be.

The functional association of antigen imprinting in SARS-CoV-2 immunization against mutants and its possible impact on (booster) vaccination methods analyze mAbs induced in individuals exposed to multiple viral variants. Important above.

In addition, research results investigating the antibody response to the development of Omicron have been published (in advance). Findings have shown that Omicron infection increases the proportion of existing Memory B cells that recognize conserved epitopes instead of inducing new B cells against Omicron-specific epitopes. This observation emphasized the importance of antigen imprinting in SARS-CoV-2. Here, the neutralizing activity of the restorative serum was enhanced not only for Omicron, but also for the previous SARS-CoV-2 VOC and the severe acute respiratory syndrome coronavirus (SARS-CoV).

Other reports suggest that the antibody prefers to recognize and neutralize the original SARS-CoV-2 strain at an early stage, suggesting that vaccine-induced memory B cells were activated early. doing.

Therefore, breakthrough infections of Omicron preferentially activate cross-reactive memory B cells. Antigen imprinting is important in determining SARS-CoV-2 immunity against viral mutations.

In addition, antigen imprinting from the parental mRNA vaccine does not affect the immune response to Omicron, so there are currently no imprint-related concerns regarding the effectiveness of current immune techniques.

Nevertheless, ambiguity remains. Future longitudinal studies will help us understand the concept of recall of SARS-CoV-2 B cells and record single antibody clones and their mutant-specific maturation.

Moreover, due to the unpredictability of future mutations, the function of antigen imprinting in SARS-CoV-2 immunity may change rapidly and significantly in the future, with overall effects favorable or detrimental. It may be. Therefore, the effects of immunological imprinting should be evaluated and measured for newly emerging viral variants and carefully observed when changing vaccination strategies.