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 Gowen; Clarence J Peters; Darci R Smith; Robert Swanepoel; John C Morrill; Thomas G Ksiazek; Phillip R Pittman; Brian H Bird; George Bettinger

doi:10.1016/j.jvacx.2020.100060

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

Vaccine X. 2020 Apr 9:5:100060. doi: 10.1016/j.jvacx.2020.100060. eCollection 2020 Aug 7.

Authors

Affiliations

¹ Managing Partner and Chief Scientific Officer, Crozet BioPharma LLC, Devens, MA, USA.
² Professor of Veterinary Arbovirology, Department of Virology, Wageningen Bioveterinary Research, Lelystad, the Netherlands.
³ 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.
⁴ Pathobiological Sciences, Louisiana State University, School of Veterinary Medicine, Baton Rouge, LA, USA.
⁵ 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.
⁶ Utah State University, Logan, UT, USA.
⁷ Professor (Emeritus) Departments of Microbiology & Immunology and Pathology Director (Emeritus) for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX, USA.
⁸ Immunodiagnostics Department, Naval Medical Research Center, Biological Defense Research Directorate, Fort Detrick, MD, USA.
⁹ Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Gauteng, South Africa.
¹⁰ Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
¹¹ U.S. Army Medical Research Institute of Infectious Diseases, Medical Research and Materiel Command, Fort Detrick, Frederick, MD, USA.
¹² 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.
¹³ University of California, Davis, One Health Institute, School of Veterinary Medicine, Davis 956164, CA, USA.
¹⁴ USAID Rift Valley Fever Vaccine Project at The University of Texas at El Paso, El Paso, TX, USA.

Abstract

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.

Keywords: Genetic reassortment; Rift Valley Fever vaccine; Target Product Profile.

Publication types

Review