Safety and Immunogenicity of an rVSV Lassa Fever Vaccine Candidate

Elissa Malkin, Vaccine Research Unit, George Washington University, Washington, DC.
Marija Zaric, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Mark Kieh, Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia.
Lindsey R. Baden, Brigham and Women's Hospital, Boston.
David Fitz-Patrick, East-West Medical Research Institute, Honolulu.
Arianna Marini, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Heejin Yun, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Peter Hayes, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Rachel Bromell, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Morolayo Ayorinde, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Natalia Fernandez, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Ruhani Varma, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Faith Sigei, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Matthew Ward, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Hema Pindolia, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Shayna Sewell, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Fahimah Amini, International AIDS Vaccine Initiative (IAVI) Human Immunology Laboratory, Imperial College London, London.
Julie Blie, Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia.
Barthalomew Wilson, Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia.
Patrick Faley, Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia.
John McCullough, Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia.
Franklin Tokpah, Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia.
Cecelia Wisseh, Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia.
Elvis Towalid, Partnership for Research on Vaccines and Infectious Diseases in Liberia, Monrovia.
Swapnil Hadawale, IAVI, New York.
Eddy Sayeed, IAVI, New York.
Devin Hunt, IAVI, New York.
Nahid Keshavarzi, IAVI, New York.
Burc Barin, Emmes, Rockville, MD.
Irina Maljkovic Berry, Integrated Research Facility at Fort Detrick, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, MD.
Christopher L. Parks, IAVI, New York.
Shobhna Gopal Truter, IAVI, New York.

Document Type

Journal Article

Publication Date

11-6-2025

Journal

The New England journal of medicine

Volume

393

Issue

18

DOI

10.1056/NEJMoa2501073

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: In this phase 1, double-blind trial conducted in the United States and Liberia, we randomly assigned healthy adults (18 to 50 years of age) to receive rVSVΔG-LASV-GPC or placebo intramuscularly. Participants received a single vaccine dose of 2×10 plaque-forming units (PFU), 2×10 PFU, 2×10 PFU, or 2×10 PFU or placebo or received two vaccine doses of 2×10 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.).

Department

Medicine

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