An adjuvanted herpes simplex virus 2 subunit vaccine elicits a T cell response in mice and is an effective therapeutic vaccine in Guinea pigs.
Immunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2ΔTMR340-363) and a truncated form of infected cell polypeptide 4 (ICP4383-766), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4(+) and CD8(+) T cells characterized by the secretion of multiple cytokines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003- or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease.
Genocea Biosciences, Inc., Cambridge, Massachusetts, USA.
Mojca
M
Skoberne
Rhonda
R
Cardin
Alexander
A
Lee
Ana
A
Kazimirova
Veronica
V
Zielinski
Danielle
D
Garvie
Amy
A
Lundberg
Shane
S
Larson
Fernando J
FJ
Bravo
David I
DI
Bernstein
Jessica B
JB
Flechtner
Deborah
D
Long
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D016367:Baculoviridae; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology* / Q000628:therapy; D018258:Herpesvirus 2, Human / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology*; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology* / Q000494:pharmacology; D017201:Virus Shedding / Q000276:immunology
D000276:Adjuvants, Immunologic; D017931:DNA Primers; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C040570:glycoprotein D-herpes simplex virus type 2