Safety and Immunogenicity of an rVSV Lassa Fever Vaccine Candidate
11/2025
Journal Article
Authors:
Malkin, E.;
Zaric, M.;
Kieh, M.;
Baden, L. R.;
Fitz-Patrick, D.;
Marini, A.;
Yun, H.;
Hayes, P.;
Bromell, R.;
Ayorinde, M.;
Fernandez, N.;
Varma, R.;
Sigei, F.;
Ward, M.;
Pindolia, H.;
Sewell, S.;
Amini, F.;
Blie, J.;
Wilson, B.;
Faley, P.;
McCullough, J.;
Tokpah, F.;
Wisseh, C.;
Towalid, E.;
Hadawale, S.;
Sayeed, E.;
Hunt, D.;
Keshavarzi, N.;
Barin, B.;
Maljkovic Berry, I.;
Parks, C. L. ;
Truter, S. G.;
Walker, K.;
Vekemans, J.;
Lehrman, J.;
Engelbrecht, M.;
Malherbe, M.;
Laufer, D.;
Philiponis, V.;
Higgs, E.;
Mutua, G.;
Fast, P. E.;
Gupta, S. B.;
r, VSVDeltaG-Lasv- G. P. C. Study Group
Volume:
393
Pagination:
1807-1818
Issue:
18
Journal:
N Engl J Med
PMID:
41191941
URL:
https://www.ncbi.nlm.nih.gov/pubmed/41191941
Keywords:
Humans Adult Male *Lassa Fever/prevention & control/immunology Double-Blind Method *Lassa virus/immunology/genetics Female Middle Aged Antibodies, Viral/blood Young Adult *Immunogenicity, Vaccine
Adolescent *Viral Vaccines/adverse effects/immunology Vaccines, Synthetic/immunology/adverse effects Antibodies, Neutralizing/blood Injections, Intramuscular
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, rVSVDeltaG-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 rVSVDeltaG-LASV-GPC or placebo intramuscularly. Participants received a single vaccine dose of 2x10(4) plaque-forming units (PFU), 2x10(5) PFU, 2x10(6) PFU, or 2x10(7) PFU or placebo or received two vaccine doses of 2x10(7) 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 rVSVDeltaG-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.).