Evaluation of Andes virus vaccine-derived human antibody for protection in Syrian hamsters: a passive transfer study using phase 1 trial sera
Abstract
Background: Andes virus (ANDV) causes severe hantavirus pulmonary syndrome and is uniquely capable of person-to-person transmission, with no licenced vaccines or therapeutics available. A Phase 1 trial ( NCT03682107 ) demonstrated that an ANDV DNA vaccine targeting Gn/Gc envelope proteins elicits neutralising antibodies in humans. We evaluated whether these human antibodies protect against lethal disease in an animal model. Methods: Day 197 sera from vaccinated human subjects were pooled, purified, and passively transferred to female Syrian hamsters one day prior to lethal ANDV challenge across two independent experiments. Controls included normal human IgG, PBS (negative controls), and SAB-400 (positive control). Neutralising antibody levels were quantified using pseudovirion neutralisation assays (PsVNA) and plaque reduction neutralisation tests (PRNT) to determine exploratory cutoff titres predicting survival. Findings: Human antibodies from DNA-vaccinated subjects—unlike normal IgG—conferred significant protection against lethal ANDV challenge in both experiments. The exploratory cutoff titres predicting protection were determined to be 31–184 for PsVNA50 and 20–80 for PRNT50, depending on the analysis population and model parameters. Interpretation: Vaccine-induced human antibodies are sufficient to protect against lethal ANDV infection in an established animal model. If confirmed, these results indicate that neutralising antibody titres could serve as a surrogate endpoint and correlate of protection for future hantavirus Gn/Gc-targeted vaccines. Funding: Defense Health Program and the National Institutes of Health (NIH).
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BibTeX
@article{hooper2026evaluation,
title = {{Evaluation of Andes virus vaccine-derived human antibody for protection in Syrian hamsters: a passive transfer study using phase 1 trial sera}},
author = {Jay W. Hooper and Sydney Lesko and Lucia Principe and Matthew Josleyn and Steve Kwilas and Sarah Norris and Kay M. Tomashek and Grant Paulsen},
journal = {eBioMedicine},
year = {2026},
month = oct,
doi = {10.1016/j.ebiom.2026.106535},
url = {https://linkinghub.elsevier.com/retrieve/pii/S2352396426004196},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Evaluation of Andes virus vaccine-derived human antibody for protection in Syrian hamsters: a passive transfer study using phase 1 trial sera
AU - Jay W. Hooper
AU - Sydney Lesko
AU - Lucia Principe
AU - Matthew Josleyn
AU - Steve Kwilas
AU - Sarah Norris
AU - Kay M. Tomashek
AU - Grant Paulsen
PY - 2026
DA - 2026/10/30
JO - eBioMedicine
DO - 10.1016/j.ebiom.2026.106535
UR - https://linkinghub.elsevier.com/retrieve/pii/S2352396426004196
AB - Background: Andes virus (ANDV) causes severe hantavirus pulmonary syndrome and is uniquely capable of person-to-person transmission, with no licenced vaccines or therapeutics available. A Phase 1 trial ( NCT03682107 ) demonstrated that an ANDV DNA vaccine targeting Gn/Gc envelope proteins elicits neutralising antibodies in humans. We evaluated whether these human antibodies protect against lethal disease in an animal model. Methods: Day 197 sera from vaccinated human subjects were pooled, purified, and passively transferred to female Syrian hamsters one day prior to lethal ANDV challenge across two independent experiments. Controls included normal human IgG, PBS (negative controls), and SAB-400 (positive control). Neutralising antibody levels were quantified using pseudovirion neutralisation assays (PsVNA) and plaque reduction neutralisation tests (PRNT) to determine exploratory cutoff titres predicting survival. Findings: Human antibodies from DNA-vaccinated subjects—unlike normal IgG—conferred significant protection against lethal ANDV challenge in both experiments. The exploratory cutoff titres predicting protection were determined to be 31–184 for PsVNA50 and 20–80 for PRNT50, depending on the analysis population and model parameters. Interpretation: Vaccine-induced human antibodies are sufficient to protect against lethal ANDV infection in an established animal model. If confirmed, these results indicate that neutralising antibody titres could serve as a surrogate endpoint and correlate of protection for future hantavirus Gn/Gc-targeted vaccines. Funding: Defense Health Program and the National Institutes of Health (NIH).
SN - 2352-3964
ER -