Phase I dose-escalation study of a monovalent heat shock protein 70-herpes simplex virus type 2 (HSV-2) peptide-based vaccine designed to prime or boost CD8 T-cell responses in HSV-naïve and HSV-2-infected subjects.
This was a phase I study to assess the safety, tolerability, and immunogenicity of escalating doses of AG-702, a noncovalent complex of an HLA A*0201-restricted epitope in the glycoprotein B protein of herpes simplex virus type 2 (gB2) and truncated human constitutive heat shock protein 70. Similar vaccines have been immunogenic in animals. Three injections of 10 to 250 mug were administered intradermally to HLA A*0201-bearing subjects who were either herpes simplex virus type 2 (HSV-2)-infected or HSV uninfected. Sixty-two participants received the vaccine, 60 completed the protocol, and T-cell data were accrued for 56 subjects. The vaccine was safe and well tolerated. New or boosted responses to the HSV-2 CD8 epitope were not detected. Baseline responses to an epitope in virion proteins 13/14 were higher than responses to the gB2 epitope. A heat shock protein vaccine with an HSV-2 peptide appears to be safe at the doses studied in healthy adults with or without HSV infection. Modifications of the dose, adjuvant, route, schedule, or HSV antigen may be required to improve responses.
Koelle
David M
DM
Department of Medicine, University of Washington, Seattle, Washington 98195, USA. viralimm@u.washington.edu
Magaret
Amalia
A
McClurkan
Christopher L
CL
Remington
Michael L
ML
Warren
Terri
T
Teofilovici
Florentina
F
Wald
Anna
A
D000293:Adolescent; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015234:HLA-A Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology* / Q000378:metabolism; D006558:Herpes Genitalis / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D018258:Herpesvirus 2, Human / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D012449:Safety; D022223:Vaccines, Subunit / Q000008:administration & dosage; D014759:Viral Envelope Proteins / Q000276:immunology
D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D018840:HSP70 Heat-Shock Proteins; D022301:Herpes Simplex Virus Vaccines; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2