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 ELISAantibody 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.
RCT Entities:
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-seropositivepatients, 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-seropositivepatients 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.
Authors: Mina Kalantari-Dehaghi; Sookhee Chun; Aziz Alami Chentoufi; Jozelyn Pablo; Li Liang; Gargi Dasgupta; Douglas M Molina; Algis Jasinskas; Rie Nakajima-Sasaki; Jiin Felgner; Gary Hermanson; Lbachir BenMohamed; Philip L Felgner; D Huw Davies Journal: J Virol Date: 2012-02-08 Impact factor: 5.103
Authors: Barbara C Baudner; Vanessa Ronconi; Daniele Casini; Marco Tortoli; Jina Kazzaz; Manmohan Singh; Lynn D Hawkins; Andreas Wack; Derek T O'Hagan Journal: Pharm Res Date: 2009-03-03 Impact factor: 4.200
Authors: Robert B Belshe; Peter A Leone; David I Bernstein; Anna Wald; Myron J Levin; Jack T Stapleton; Iris Gorfinkel; Rhoda L Ashley Morrow; Marian G Ewell; Abbie Stokes-Riner; Gary Dubin; Thomas C Heineman; Joann M Schulte; Carolyn D Deal Journal: N Engl J Med Date: 2012-01-05 Impact factor: 91.245
Authors: Kevin Egan; Lauren M Hook; Philip LaTourette; Angela Desmond; Sita Awasthi; Harvey M Friedman Journal: Transl Res Date: 2020-03-16 Impact factor: 7.012