From concept to delivery: a yeast-expressed recombinant protein-based COVID-19 vaccine technology suitable for global access

ABSTRACT

Introduction

The development of a yeast-expressed recombinant protein-based vaccine technology co-developed with LMIC vaccine producers and suitable as a COVID-19 vaccine for global access is described. The proof-of-concept for developing a SARS-CoV-2 spike protein receptor-binding domain (RBD) antigen as a yeast-derived recombinant protein vaccine technology is described.

Areas Covered

Genetic Engineering: The strategy is presented for the design and genetic modification used during cloning and expression in the yeast system. Process and Assay Development: A summary is presented of how a scalable, reproducible, and robust production process for the recombinant protein COVID-19 vaccine antigen was developed. Formulation and Pre-clinical Strategy: We report on the pre-clinical and formulation strategy used for the proof-of-concept evaluation of the SARS-CoV-2 RBD vaccine antigen. Technology Transfer and Partnerships: The process used for the technology transfer and co-development with LMIC vaccine producers is described. Clinical Development and Delivery: The approach used by LMIC developers to establish the industrial process, clinical development, and deployment is described.

Expert Opinion

Highlighted is an alternative model for developing new vaccines for emerging infectious diseases of pandemic importance starting with an academic institution directly transferring their technology to LMIC vaccine producers without the involvement of multinational pharma companies.

KEYWORDS:

• SARS
• SARS-CoV-2
• COVID-19
• vaccine
• recombinant protein
• microbial fermentation
• CORBEVAX
• INDOVAC

Article highlights

• The COVID-19 pandemic revealed profound vaccine inequalities due in part to the absence of new vaccines developed and produced by manufacturers in low- and middle-income countries (LMICs).

• Texas Children’s CVD works with LMIC vaccine producers to develop recombinant protein vaccines through microbial fermentation in yeast. So far, more than 73 million doses have been administered for primary immunizations in children, as well as several million adult booster doses.

• Proof-of-concept for the protective immunity elicited by yeast-derived spike protein receptor-binding domain (RBD) antigens for both severe acute respiratory syndrome (SARS) and COVID-19 caused by the SARS-CoV-2 coronavirus was obtained in animal challenge models.

• The modifications for each RBD improve immunogenicity and production efficiency and reduce costs.

• The SARS-CoV-2 RBD219-N1C1 antigen for COVID-19 was technology transferred to Biological E in India, where it was produced at an industrial scale and formulated with aluminum hydroxide and CpG1018 (Dynavax Technologies) to produce CORBEVAX.

• In phase 1-2 clinical trials, CORBEVAX was shown to be safe and immunogenic and was authorized for emergency use following a phase 3 superiority study with a comparator COVID-19 vaccine produced in India.

• In Indonesia, the vaccine producer BioFarma developed IndoVac, a similar RBD COVID-19 vaccine with Texas Children’s CVD technology, where it has received emergency use authorization. IndoVac takes advantage of its vegan properties to designate it as halal for Muslim-majority countries.

• The activities reported here highlight an alternative for developing new vaccines for emerging infections outside of the multinational pharma companies.

• Now, this approach is being tapped to create variant-specific booster shots, possibly including one to prevent the Omicron BA.5 subvariant, as well as universal coronavirus vaccines.

Declaration of interest

The team of scientists at Texas Children’s Hospital Center for Vaccine Development including its co-directors, Professors Peter Hotez and Maria Elena Bottazzi, are co-inventors of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was recently licensed by BCM non-exclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. The co-inventors are not involved in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries that result in a commercial license, a share of any royalty income. 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

Reviewer disclosures

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

Additional information

Funding

This paper was funded by Fifth Generation, Inc, JPB Foundation, NIH/NIAID (AI14087201) and the Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation, as well as philanthropic funds received by and intramural funding from Texas Children’s Hospital Center for Vaccine Development at Baylor College of Medicine.