A recombinant glycoprotein vaccine for herpes simplex virus type 2: safety and immunogenicity [corrected].
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.


METHODS
Integrated summary of two phase I and two phase II studies.


METHODS
University and private outpatient clinics.


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


METHODS
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.


METHODS
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.
Langenberg
A G
AG
Chiron Biocine, Emeryville, California, USA.
Burke
R L
RL
Adair
S F
SF
Sekulovich
R
R
Tigges
M
M
Dekker
C L
CL
Corey
L
L
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000917:Antibody Formation; D006023:Glycoproteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006558:Herpes Genitalis / Q000517:prevention & control*; D018258:Herpesvirus 2, Human; D006801:Humans; D007156:Immunologic Memory; D008875:Middle Aged; D011136:Polysorbates / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D013185:Squalene / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology; D014765:Viral Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D006023:Glycoproteins; C089950:MF59 oil emulsion; D011136:Polysorbates; D011994:Recombinant Proteins; D014765:Viral Vaccines; D013185:Squalene