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Immunogenicity of an adjuvanted, combination inactivated rabies-vectored, Lassa fever vaccine in healthy adults: interim results of a first-in-human Phase 1 trial

Ortiz, J. R.; Kurup, D.; Kaufman, A. C.; Ben Hamed, S.; LaRocco, A.; Lyke, K. E.; Litts, S.; Datta, S.; Liang, Y.; McGilvray, M. F.; Losignor, J.; Oshinsky, J. J.; Palmer, K. V.; Mayo-Johnson, I. P.; Scher, G.; Balakumar, U.; Chandwani, A.; Rapaka, R. R.; Deming, M. E.; Chua, J. V.; Wirblich, C.; Chen, W. H.; Neuzil, K. M.; Pasetti, M.; Schnell, M.

2025-10-17 infectious diseases
10.1101/2025.10.16.25338178 medRxiv
Show abstract

We conducted a randomized, controlled Phase 1 trial of an inactivated rabies virus-vectored Lassa virus glycoprotein complex (GPC) vaccine (LASSARAB) formulated with a synthetic oil-in-water TLR-4 agonist adjuvant (3D-6acyl PHAD-SE). In dose-escalating cohorts, participants received two intramuscular doses of LASSARAB containing 700 (n=15), 1400 (n=15), or 2800 (n=14) relative units of antigen, as quantified by ELISA using recombinant GPC as a standard, or a licensed rabies vaccine control (n=10), administered 28 days apart. This interim analysis reports the primary objective of safety evaluation and the secondary objective of immunogenicity assessment through Day 61. All doses were well tolerated. After two doses, Lassa GPC ELISA seroconversion rates were 100% in all LASSARAB groups and 0% in the control group. Rabies glycoprotein ELISA seroconversion and neutralizing antibody seroprotection were both 100% across all groups, including controls. This first-in-human study demonstrates that LASSARAB+3D-6acyl PHAD-SE is a well-tolerated, highly immunogenic, combination vaccine, supporting further clinical evaluation. ClinicalTrials.gov identifier: NCT06546709.

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