Original antigen sin and COVID-19: implications for seasonal vaccination

ABSTRACT

Introduction

Original antigenic sin describes the phenomenon in which immunity against pathogens or antigens is shaped by the host’s first exposure to a related pathogen or antigen.

Areas covered

When primary immunity is boosted not by the homologous but by a cross-reacting vaccine, the newly formed antibodies may react better with the primary antigen than with the antigen actually eliciting the response. This form of immune imprinting, which has been observed with influenza, dengue, human immunodeficiency virus, and other pathogens, has profound implications for the approach to seasonal vaccination against a variety of diseases, including COVID-19.

Expert opinion

Public health agencies and regulatory bodies have consistently recommended repeated vaccinations every few months as a way to protect against COVID-19. However, the risks and benefits of this approach require scrutiny given the concern for original antigenic sin in response to SARS-CoV-2. This manuscript examines what is known about immune imprinting and looks ahead to explore how this phenomenon may impact seasonal vaccination against emerging SARS-CoV-2 subvariants such as BA.4, BA.5, and BA.5.1, which have been associated with increased transmissibility due to enhanced immune escape.

KEYWORDS:

• SARS-CoV-2
• COVID-19
• omicron
• BA.5
• immune imprinting

Article highlights

• Original antigenic sin is an asymmetric pattern of protective antibody cross-reactivity determined by exposure to previously existing strains of a given pathogen

• This phenomenon is most commonly observed in response to viruses, such as dengue, human immunodeficiency virus, and rotavirus.

• It is not clear how repeated vaccination against SARS-CoV-2 will alter the human immune system

• Original antigenic sin is governed by B and T cell responses

• Original antigenic sin may impact the timing of COVID-19 boosters and the risks of sequential vaccination must be considered for low-risk patients.

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.