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ARTICLE

A Recombinant Glycoprotein Vaccine for Herpes Simplex Type 2: Safety and Efficacy

Andria G. M. Langenberg; Rae Lyn Burke; Suzanne F. Adair; Rose Sekulovich; Michael Tigges; Cornelia L. Dekker; and Lawrence Corey

15 June 1995 | Volume 122 Issue 12 | Pages 889-898

Objective: To evaluate the safety and immunogenicity of a recombinant glycoprotein vaccine for herpes simplex virus type 2 (HSV-2), which contains glycoproteins gD2 and gB2 combined with the novel MF59 adjuvant emulsion, in HSV-2-seronegative persons.

Design: Integrated summary of two phase I and two phase II studies.

Setting: University and private outpatient clinics.

Patients: 137 persons seronegative for HSV-2 antibodies as determined by HSV Western blot assay.

Intervention: Open-label vaccine administration with a dose-escalating design (phase I) was followed by randomized vaccine administration (phase II). Vaccine was administered intramuscularly into the deltoid at 0, 1, and 6 months.

Measurements: Neutralizing, HSV-2-binding antibodies and HSV-2-stimulated proliferative responses were measured before and after immunization.

Results: Among HSV-seronegative patients, the gD2 and gB2 enzyme-linked immunosorbent assay (ELISA) and HSV-2-neutralizing antibody titers increased to levels equal to or higher than those seen in naturally acquired HSV-2 infection after the full three-dose immunization schedule. Among HSV-1-seropositive patients, one immunization produced increases in gD2 and gB2 ELISA antibody titers and HSV-2-neutralizing antibody titers that were 3 to 5 times greater than those in persons with naturally acquired HSV-2 infection. Among HSV-seronegative patients, frequency analysis assays showed a marked increase in the precursor frequency of gD2- and gB2-specific T cells after vaccination: T-cell responses after two immunizations were equal to the responses of HSV-2-seropositive patients and were sustained at day 180. The vaccine was well tolerated.

Conclusions: This subunit vaccine induces both humoral and cellular responses to HSV-2 that are equal to or greater than those of persons with naturally acquired HSV-2 infection. Studies to evaluate this vaccine for the prevention of genital herpes appear warranted.

Author and Article Information

From Chiron Biocine, Emeryville, California, and the University of Washington School of Medicine, Seattle, Washington.
Requests for Reprints: Andria Langenberg, MD, Chiron Biocine, Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608.
Note: Dr. Corey serves as a consultant to the Chiron Biocine's vaccine research program.
Grant Support: By Chiron Biocine and National Institutes of Health Grant AI-30731 (Dr. Corey).
Acknowledgments: The authors thank N. Niland, MD, B. Levy, MD, and Peter Trethewey; Rhoda Ashley, PhD, for performing the Western blot studies; Marietta Marcus, Lisa Stoll, Susan Klein, Denise Portello, Cheryl Goldbeck, and Philip Ng for technical assistance; and Allen Izu, MS, Jane Porter, and Jim Thomas for statistical support.

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