Theoretical risk of genetic reassortment should not impede development of live, attenuated Rift Valley fever (RVF) vaccines commentary on the draft WHO RVF Target Product Profile
Thomas P. Monath,
Jeroen Kortekaas,
Douglas M. Watts,
Rebecca C. Christofferson,
Angelle Desiree LaBeaud,
Brian B Gowen,
Clarence J. Peters,
Darci R. Smith,
Robert Swanepoel,
John C. Morrill,
Thomas G. Ksiazek,
Phillip R Pittman,
Stuart T. Nichol,
Brian H. Bird,
George Bettinger
Affiliations
Thomas P. Monath
Managing Partner and Chief Scientific Officer, Crozet BioPharma LLC, Devens, MA, USA
Jeroen Kortekaas
Professor of Veterinary Arbovirology, Department of Virology, Wageningen Bioveterinary Research, Lelystad, the Netherlands
Douglas M. Watts
Executive Director of Vet Services, and Director of Biosafety Level 3 Laboratory and Co-Director of BBRC Infectious Disease and Immunology, University of Texas at El Paso, El Paso, TX, USA
Rebecca C. Christofferson
Pathobiological Sciences, Louisiana State University, School of Veterinary Medicine, Baton Rouge, LA, USA
Angelle Desiree LaBeaud
Professor of Pediatrics (Infectious Diseases), Stanford University School of Medicine, Senior Fellow at the Woods Institute for the Environment and Professor of Health Research and Policy (Epidemiology) at the Lucile Salter Packard Children's Hospital, Stanford, CA, USA
Brian B Gowen
Utah State University, Logan, UT, USA
Clarence J. Peters
Professor (Emeritus) Departments of Microbiology & Immunology and Pathology Director (Emeritus) for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA
Darci R. Smith
Immunodiagnostics Department, Naval Medical Research Center, Biological Defense Research Directorate, Fort Detrick, MD, USA
Robert Swanepoel
Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Gauteng, South Africa
John C. Morrill
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
Thomas G. Ksiazek
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA
Phillip R Pittman
U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD, USA
Stuart T. Nichol
Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA
Brian H. Bird
University of California, Davis, One Health Institute, School of Veterinary Medicine, Davis 956164, CA, USA
George Bettinger
USAID Rift Valley Fever Vaccine Project at The University of Texas at El Paso, El Paso, TX, USA
In November 2019, The World Health Organization (WHO) issued a draft set of Target Product Profiles (TPPs) describing optimal and minimally acceptable targets for vaccines against Rift Valley fever (RVF), a Phlebovirus with a three segmented genome, in both humans and ruminants. The TPPs contained rigid requirements to protect against genomic reassortment of live, attenuated vaccines (LAVs) with wild-type RVF virus (RVFV), which place undue constraints on development and regulatory approval of LAVs. We review the current LAVs in use and in development, and conclude that there is no evidence that reassortment between LAVs and wild-type RVFV has occurred during field use, that such a reassortment event if it occurred would have no untoward consequence, and that the TPPs should be revised to provide a more balanced assessment of the benefits versus the theoretical risks of reassortment.
