Nonhuman primate models for evaluation of SARS-CoV-2 vaccines

ABSTRACT

Introduction

Evaluation of immunogenicity and efficacy in animal models provide critical data in vaccine development. Nonhuman primates (NHPs) have been used extensively in the evaluation of SARS-CoV-2 vaccines.

Areas Covered

A critical synthesis of SARS-CoV-2 vaccine development with a focus on challenge studies in NHPs is provided. The benefits and drawbacks of the NHP models are discussed. The citations were selected by the authors based on PubMed searches of the literature, summaries from national public health bodies, and press-release information provided by vaccine developers.

Expert Opinion

We identify several aspects of NHP models that limit their usefulness for vaccine-challenge studies and numerous variables that constrain comparisons across vaccine platforms. We propose that studies conducted in NHPs for vaccine development should use a standardized protocol and, where possible, be substituted with smaller animal models. This will ensure continued rapid progression of vaccines to clinical trials without compromising assessments of safety or efficacy.

KEYWORDS:

• SARS-CoV-2
• COVID-19
• non-human primates
• vaccine-challenge
• animal models

Article highlights

• Several SARS-CoV-2 vaccines demonstrated safety and efficacy in NHPs prior to commencement of clinical trials.

• We provide a comprehensive comparison of the study designs and outcomes between these NHP studies.

• We identify considerable variability between study designs and efficacy measurements.

• Inconsistent infection of control animals and lack of detection of infectious virus were concerning.

• Benefits and drawbacks of using NHP models for SARS-CoV-2 vaccine development are discussed.

• Our findings support the usefulness of standardized protocols and alternative disease models of SARS-CoV-2 infection for future vaccine development.

Declaration of Interests

K Subbarao is a member of the COVAX Independent Product Group and WHO EUL committee. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. D Godfrey has four Australian Provisional Patent Applications related to COVID-19 research pending. S Rockman is an employee of Seqirus and holds shares in the parent company CSL Ltd that manufactures influenza vaccine for worldwide distribution.

Reviewer disclosures

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

Author contributions

All authors substantially contributed to the conception and design of the review article and interpretation of the relevant literature. J.A. Neil, K. Subbarao and T. Nolan wrote the manuscript. All other authors revised the manuscript for intellectual content.

Additional information

Funding

This work was funded by the National Health and Medical Research Council, Medical Research Future Fund, Victorian Government DHHS, Jack Ma Foundation, and Paul Ramsay Foundation.