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

Andria G. M. Langenberg, MD; Rae Lyn Burke, PhD; Suzanne F. Adair, PhD; Rose Sekulovich, PhD; Michael Tigges, PhD; Cornelia L. Dekker, MD; and Lawrence Corey, MD
[+] Article and Author 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.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1995;122(12):889-898. doi:10.7326/0003-4819-122-12-199506150-00001
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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.

Figures

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Figure 1.
Geometric mean enzyme-linked immunosorbent assay(ELISA) titers to herpes simplex virus type 2 (HSV-2) glycoproteins D2 and B2 before and after immunization with recombinant subunit HSV-2 vaccine in MF59.

Arrows denote days of vaccination (days 0, 28, and 180). The standard error and 95% CIs as compared with baseline values are given in the text. The dose of each glycoprotein at each injection and the number of patients receiving each dose are shown. The geometric mean titer (GMT) to glycoproteins B2 and D2 for persons with naturally acquired HSV-2 infection are 3560 and 1209, respectively (see text). HSV = herpes simplex virus.

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Figure 2.
Top.Bottom.

Herpes simplex virus type 2 (HSV-2) neutralizing antibodies in persons with naturally acquired herpes simplex virus type 1 (HSV-1) and HSV-2 infection. One hundred thirty-three patients were seropositive for only HSV-2 by Western blot, and 249 patients were HSV-1-seropositive only. Herpes simplex virus type 2 neutralizing antibodies in patients 2 weeks after the third immunization with the 30- micrograms vaccine. Twenty-three patients were HSV-seronegative, and 15 were HSV-1-seropositive. Asterisk indicates the dilution at which there is 50% inhibition of cytolysis of the cell monolayer.

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Figure 3.
Geometric mean herpes simplex virus neutralizing antibody titers for patients who had all three immunizations.Figure 2

Seropositive and seronegative status refers to status at study entry; arrows denote days of vaccination (days 0, 28, and 180). The dose of each glycoprotein and the number of patients receiving each dose are shown. The geometric mean titer neutralizing titer ±SE for persons with naturally acquired herpes simplex virus type 2 (HSV-2) was 141 (CI, 141 x/÷ 1.14) (see text and , top). HSV-1 = herpes simplex virus type 1.

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