Clinical development of variant-adapted BNT162b2 COVID-19 vaccines: the early Omicron era

ABSTRACT

Introduction

The Omicron BA.1 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and subsequent sub-lineages exhibit partial escape from neutralizing antibodies elicited by vaccines containing or encoding wild-type spike protein. In response to the emergence of Omicron sub-lineages, variant-adapted vaccines that contain or encode for Omicron spike protein components have been developed.

Areas covered

This review presents currently available clinical immunogenicity and safety data on Omicron variant-adapted versions of the BNT162b2 messenger RNA (mRNA) vaccine and summarizes the expected mechanism of action, and rationale for development, of these vaccines. In addition, challenges encountered during development and regulatory approval are discussed.

Expert opinion

Omicron-adapted BNT162b2 vaccines provide a wider breadth and potentially more durable protection against Omicron sub-lineages and antigenically aligned variants when compared with the original vaccine. As SARS-CoV-2 continues to evolve, further vaccine updates may be required. To facilitate this, a globally harmonized regulatory process for the transition to updated vaccines is needed. Next-generation vaccine approaches may provide broader protection against future variants.

KEYWORDS:

• COVID-19
• SARS-CoV-2
• BNT162b2
• variant of concern
• Omicron
• bivalent vaccines

Article highlights

• This review presents an overview of the clinical development and approval of Omicron variant-adapted versions of the BNT162b2 mRNA COVID-19 vaccine.

• Bivalent BNT162b2 vaccines containing an Omicron BA.1 or BA.4/5 component in addition to the original wild-type component have been shown to provide improved neutralization of Omicron sub-lineages while maintaining neutralizing antibody activity against wild-type SARS-CoV-2 at a level similar to that of the original BNT162b2 vaccine.

• The reactogenicity and safety profile of the bivalent BNT162b2 vaccines is consistent with that of the original vaccine.

• Challenges, such as the ongoing emergence of new SARS-CoV-2 variants with immune escape mechanisms and differences across regulatory bodies in decision-making and guidance on vaccine composition, affected the time to approval and roll-out, highlighting a need for a global harmonized regulatory process prior to future vaccine updates.

Acknowledgments

Medical writing support, including assisting authors with the development of the outline and initial draft and incorporation of comments was provided by Rachel Wright, PhD, and editorial support was provided by Ian Norton, PhD, both of Scion, London, UK, supported by BioNTech SE according to Good Publication Practice guidelines (Link).

Declaration of interest

A Muik, S Pather, F Mensa, and R Rizzi are employees at BioNTech SE (Mainz, Germany). A Muik is an inventor on patents and patent applications related to RNA technology and COVID-19 vaccines. A Muik, S Pather, F Mensa, and R Rizzi have securities from BioNTech SE. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Author contributions

All authors substantially contributed to the manuscript conception, interpretation of relevant literature, writing, and review process, and approved the final version for submission.

Additional information

Funding

This manuscript was funded by BioNTech SE.