Pivoting to protein: the immunogenicity and safety of protein-based NVX-CoV2373 as a heterologous booster for inactivated and viral vector COVID-19 vaccines

ABSTRACT

Introduction

Approximately half of the 13.4 billion COVID-19 vaccine doses administered globally were inactivated or viral vector platforms. The harmonization and optimization of vaccine regimens has become a key focus of policymakers and health-care providers and presents an opportunity to reassess the continued use of pandemic-era vaccines.

Areas covered

Immunological evidence from studies of various homologous and heterologous regimens has been rapidly published; however, interpretation of these data is complicated by the many vaccine types and highly variable participant viral exposure and vaccination histories. Recent studies demonstrate that after primary series doses of inactivated (i.e. BBV152, and BBIBP-CorV), and viral vector (ChAdOx1 nCov-2019) vaccines, a heterologous boost with protein-based NVX-CoV2373 elicits more potent ancestral strain and omicron-specific antibody responses compared to homologous and heterologous inactivated and viral vector boosts.

Expert opinion

While mRNA vaccines likely yield similar performance to protein-based heterologous booster doses, the latter offers notable advantages to countries with high uptake of inactivated and viral vector vaccines in terms of transportation and storage logistics and can potentially appeal to vaccine hesitant individuals. Moving forward, vaccine-mediated protection in inactivated and viral vector recipients may be optimized with the use of a heterologous protein-based booster such as NVX-CoV2373.

Pivoting to Protein

The Immunogenicity and Safety of Protein-based NVX-CoV2373 as a Heterologous Booster for Inactivated and Viral Vector COVID-19 Vaccines. Inactivated or viral vector primary series following a booster dose with homologous or heterologous inactivated vaccines (i.e., BBV152, BBIBP-CorV), and homologous or heterologous viral vector vaccines (i.e., ChAd-Ox1 nCov-19) induces suboptimal immunogenicity compared to the enhanced immunogenicity of heterologous protein-based vaccine NVX-CoV2373.

GRAPHICAL ABSTRACT

KEYWORDS:

• COVID-19 vaccines
• heterologous booster
• inactivated
• protein-based
• viral vector
• NVX-CoV2373

Article highlights

• The optimization of vaccine regimens is necessary to improve protection and continue to limit the spread of SARS-CoV-2

• Thus far, there has been lower global uptake of protein-based COVID-19 vaccinations compared to other platforms, but increased global authorizations and positive immunogenicity data could drive protein vaccines to be the boosters-of-choice moving forward

• Multiple studies demonstrate that the protein-based COVID-19 vaccine NVX-CoV2373 elicits robust immunogenic responses when utilized as a heterologous booster following primary vaccination with inactivated or viral vector COVID-19 vaccines

• Compared to mRNA booster options, NVX-CoV2373 may offer distinct advantages such as lower reactogenicity, which could appeal to vaccine hesitant individuals

• Future vaccination campaigns, which may include yearly COVID-19 boosters, will rely on immunogenicity studies to inform on and support the optimization of booster vaccination regimens

Declaration of interest

AM Marchese, R Kalkeri, M Vadivale, and S Toback are employees and shareholders of Novavax, Inc. 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.

Additional information

Funding

This paper was funded by Novavax, Inc.