Clinical evaluation of a vaccinia-vectored Hantaan virus vaccine

• Published in: Journal of medical virology 2000-01, Vol.60 (1), p.77-85
• Main Authors: McClain, David J., Summers, Peter L., Harrison, Stephen A., Schmaljohn, Alan L., Schmaljohn, Connie S.
• Format: Article
• Language: English
• Subjects: Antibodies, Viral - blood; Biological and medical sciences; Dose-Response Relationship, Immunologic; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Hantaan virus; Hantaan virus - genetics; Hantaan virus - immunology; hantavirus; Humans; Immunization, Secondary; Lymphocyte Activation; Microbiology; Neutralization Tests; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - immunology; Vaccinia virus; Vaccinia virus - genetics; vaccinia-vectored vaccine; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; Virology
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/(SICI)1096-9071(200001)60:1<77::AID-JMV13>3.0.CO;2-S

We evaluated a vaccinia‐vectored vaccine for hemorrhagic fever with renal syndrome in clinical trials. A Phase I dose‐escalation study in 16 volunteers divided into four groups demonstrated that subcutaneous inoculation of approximately 107 plaque‐forming units of the recombinant virus was safe and immunogenic. Vaccination of a fifth group of 12 volunteers indicated that neutralizing antibody titers to both vaccinia virus and Hantaan virus were enhanced after a second inoculation. Comparing two routes of vaccination showed that scarification effectively induced neutralizing antibodies in vaccinia virus‐naive volunteers but that subcutaneous inoculation was superior to scarification in vaccinia virus‐immune individuals. A Phase II, double‐blinded, placebo‐controlled clinical trial was conducted among 142 volunteers. Two subcutaneous vaccinations were administered at 4‐week intervals. Neutralizing antibodies to Hantaan virus or to vaccinia virus were detected in 72% or 98% of vaccinia virus‐naive volunteers, respectively. In contrast, only 26% of the vaccinia virus‐immune volunteers developed neutralizing antibody responses to Hantaan virus. J. Med. Virol. 60:77–85, 2000. Published 2000 Wiley‐Liss, Inc.