Understanding the mechanisms for COVID-19 vaccine’s protection against infection and severe disease

ABSTRACT

Introduction

Multiple COVID-19 vaccines have been approved and employed in the fight against the pandemic. However, these vaccines have limited long-term effectiveness against severe cases and a decreased ability to prevent mild disease.

Areas covered

This review discusses the relevant factors influencing the efficacy of the vaccines against mild and severe infection, analyzes the possible underlying mechanisms contributing to the different outcomes in terms of vaccine function and disease progression, and proposes improvements for the next generation of vaccines.

Expert Opinion

The reduced efficacy of the COVID-19 vaccine in the prevention of viral infection is closely related to the emergence of novel SARS-CoV-2 variants and their rapid transmission ability. Fundamentally, the immune responses induced by COVID-19 vaccines cannot effectively halt virus replication in the upper respiratory tract because only a limited number of specific antibodies reach these areas and decrease in concentration over time. However, the established immune response can provide sufficient protection against severe diseases by blocking viral infection of the lower respiratory tract or lung owing to sufficient antibody repertoires and memory responses. Considering this situation, future COVID-19 vaccines should have the potential to replenish the mucosal immune response in the respiratory tract to prevent viral infection.

KEYWORDS:

• COVID-19 vaccine
• mechanisms
• mild disease
• severe disease
• viremia
• virus variants

Article highlights

• Two significant aspects were identified during the application of the COVID-19 vaccine: the decline in efficacy of protection against mild infections and limited long-term efficacy in preventing severe diseases.

• The decline in the protective function of the vaccine against infection is consistent with the decrease in circulating antibodies in the body, which may be due to the limited exudation of antibodies into the lumen of the respiratory tract. This becomes more evident with the occurrence of virus variants, especially Omicrons, whose infection is more limited to the upper respiratory tract with a short incubation period.

• Severe disease caused by SARS-CoV-2 involves the virus transmission from the upper respiratory tract to the lower respiratory tract, lung, or other organs. The physiological structure of the lungs, especially the contact between the alveolar epithelium and capillary endothelium, provides a pathway for IgG antibody transport or exudation into the bronchial cavity and the surface of the alveoli, effectively preventing viral replication and the occurrence of severe pneumonia.

• For severe systemic disease, both memory B cells and T cells containing broad-spectrum elements against SARS-CoV-2 conserved proteins or epitopes are vital sources to stop disease progression. In addition, the neutralizing antibodies present in circulation can effectively halt viremia and consequently inhibit the spread of the virus.

• Multivalent vaccines for different variants and/or vaccines that induce mucosal immune responses are of scientific interest for improving the efficacy of the COVID-19 vaccines in the prevention of virus infection and transmission.

Declaration of interest

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

Reviewer disclosures

A reviewer on this manuscript has disclosed that they have received research grants from Moderna, Pfizer, GSK, and Astra Zeneca, and received personal fee for board participation from GSK. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Author contributions

Huijie Yang conceived and drafted the manuscript; Ying Xie offered valuable discussions and partial content; Changgui Li provided specialized guidance and revised the manuscript. All authors have read and approved this article.

Additional information

Funding

This paper was not funded.