1. Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study.
- Author
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Paulsen GC, Frenck R Jr, Tomashek KM, Alarcon RM, Hensel E, Lowe A, Brocato RL, Kwilas SA, Josleyn MD, and Hooper JW
- Subjects
- Adult, Humans, Antibodies, Neutralizing, DNA, Immunogenicity, Vaccine, Double-Blind Method, Antibodies, Viral, Orthohantavirus, Vaccines, DNA adverse effects, Hantavirus Pulmonary Syndrome
- Abstract
Background: Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated., Methods: Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50)., Results: While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197., Conclusions: This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response. Clinical Trials Registration. NCT03682107., Competing Interests: Potential conflicts of interest. J. W. H. is listed as an inventor on a patent that includes the ANDV DNA vaccine; the patent is assigned to the United States Government. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2024
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