Safety and Immunogenicity of an rVSV Lassa Fever Vaccine Candidate
Elissa Malkin, Marija Zaric, Mark Kieh, Lindsey R. Baden, David Fitzpatrick, Arianna Marini, Heejin Yun, Peter Hayes, Rachel Bromell, Morolayo A. Ayorinde, Natalia Fernández, R. N. Varma, Faith Sigei, Matthew Ward, Hema Pindolia, S. A. Sewell, Fahimah Amini, Julie Blie, Barthalomew Wilson, Patrick Faley, John McCullough, Franklin Tokpah, Cecelia Wisseh, Elvis Towalid, Swapnil Hadawale, Eddy Sayeed, Devin J Hunt, Nahid Keshavarzi, Burc Barin, Irina Maljkovic Berry, Christopher L. Parks, Shobhna Gopal Truter, Kathleen A. Walker, Johan Vekemans, Jennifer Lehrman, Michelle Engelbrecht, Mariette Malherbe, Dagna Laufer, Vincent Philiponis, Elizabeth S. Higgs, Gaudensia Mutua, Pat Fast, Swati B. Gupta
Abstract
BACKGROUND: No vaccine is currently available for Lassa fever, a viral hemorrhagic disease that is estimated to cause thousands of deaths each year in western Africa. A replication-competent recombinant vesicular stomatitis virus-vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex, rVSVΔG-LASV-GPC, has been developed, but data on its safety and immunogenicity are limited. METHODS: PFU or placebo, within a window of 6 to 20 weeks. The side-effect profile was assessed according to the incidence of solicited and unsolicited adverse events (primary end point). Because Lassa fever can cause sensorineural hearing loss, hearing acuity was measured before and after the injection. Secondary end points were levels of binding antibodies against LASV glycoprotein, neutralizing antibodies, and vaccine vector-derived viral RNA and PFU in plasma, urine, and saliva. RESULTS: A total of 114 adults were enrolled. No serious vaccine-related adverse events were reported. The vaccine caused minimal local reactions and dose-dependent, mild-to-severe early-onset systemic reactogenicity events that were transient. No hearing loss was detected. All doses induced robust long-lasting cellular and humoral (binding and neutralizing) responses that cross-reacted against common LASV lineages. No infectious vaccine virus particles were found in plasma, urine, or saliva. CONCLUSIONS: The rVSVΔG-LASV-GPC vaccine resulted in transient local and systemic reactogenicity events but no hearing loss or serious adverse events. The vaccine had immunogenicity over a wide dose range in healthy adults in the United States and Liberia. (Funded by the Coalition for Epidemic Preparedness Innovations and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04794218; Pan African Clinical Trials Registry number, PACTR2021106625781067.).