Controlled human infection models and SARS-CoV-2 vaccine development

Writing in a commentary on behalf of Accelerating COVID-19 Therapeutic Interventions and Vaccines's Vaccines Working Group, authors from the Walter Reed Army Institute of Research, University of Maryland School of Medicine, University of North Carolina School of Medicine and Henry M. Jackson Foundation for the Advancement of Military Medicine, detailed a series of scientific and ethical concerns and considerations required for robust controlled human infection models development. While CHIMs are unlikely to advance the timelines of current SARS-CoV-2 vaccines in advanced development, the authors argue, such tests may be able to accelerate later rounds of vaccine candidates.

Traditional vaccine development is typically linear, where animal then human testing informs a regulatory decision on vaccine licensure, finally allowing for mass production. In the face of the significant public health burden of COVID-19, the disease caused by SARS-CoV-2, vaccine developers have made unprecedented efforts to shorten timelines by compressing and overlapping these steps.

A component of this process is late stage efficacy trials, where large, randomized groups of study participants are vaccinated then exposed to the virus through natural transmission in their community. However, CHIMs, where healthy individuals are infected by a well-characterized virus in extremely controlled settings, have been advanced as an alternative to these trials. Several CHIMs are currently in use for other diseases, including malaria and influenza.

"CHIMs provide distinct advantages over traditional field efficacy trials, allowing researchers to answer a broader range of questions about the virus, vaccine and the body's immune response," said Dr. Nelson Michael, director of WRAIR's Center for Infectious Disease Research and an author on the commentary. "However, given that large efficacy studies are imminent and that developing a robust CHIM model will require at least one year, it is unlikely that they will significantly advance the current slate of vaccines in advanced development."

Building on the World Health Organization's essential criteria for conducting SARS-CoV-2 challenge studies, the commentary details several key considerations to address before SARS-CoV-2 CHIM studies can be implemented, including the lack of reliable treatments in case of vaccine inefficacy, risks of community transmission, access to the requisite infrastructure and understanding of the virus's progression within the body. Addressing these concerns in parallel could result in long-term discoveries to help mitigate the current and future pandemics.

Though CHIM development would be laborious, it could ultimately be advantageous, allowing researchers to answer a much broader range of questions about both the virus and vaccines designed to prevent it. Additionally, the development of CHIMs for other, less severe coronaviruses could provide meaningful insights to SARS-CoV-2 with less risk.

WRAIR is currently developing a SARS-CoV-2 vaccine, currently slated to begin human trials in early fall, as well as new diagnostics and treatments.