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

  1. Andria G. M. Langenberg, MD;
  2. Rae Lyn Burke, PhD;
  3. Suzanne F. Adair, PhD;
  4. Rose Sekulovich, PhD;
  5. Michael Tigges, PhD;
  6. Cornelia L. Dekker, MD; and
  7. Lawrence Corey, MD
  1. 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.

    Abstract

    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.

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    1. Ann Intern Med June 15, 1995 vol. 122 no. 12 889-898
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