The HSV-1 live attenuated VC2 vaccine provides protection against HSV-2 genital infection in the guinea pig model of genital herpes.
BACKGROUND
Although development of an HSV vaccine is a priority there is currently no vaccine available. The recent failure of subunit vaccines suggest that presentation of more antigens via a live attenuated vaccine may be required for protection. We therefore evaluated VC2, a live attenuated HSV vaccine, engineered to be unable to enter into neuronal axons.


METHODS
VC2 pathogenesis was first evaluated in guinea pigs following intravaginal inoculation. VC2 was then evaluated as a prophylactic and therapeutic vaccine and compared protection to a gD2 vaccine adjuvanted with MPL/Alum in the guinea pig model of genital HSV-2. The guinea pig model allows evaluation of acute and recurrent disease, as well as vaginal shedding acutely and during episodes of recurrent activation.


RESULTS
VC2 was significantly attenuated in guinea pigs compared to the wild type strain, 17syn+. It replicated poorly at the inoculation site, did not produce any genital disease and rarely infected the neural tissue. After prophylactic vaccination, the VC2 vaccine decreased the clinical severity of acute and recurrent HSV-2 disease and shedding and decreased the quantity of virus in the DRGs. When compared to gD2+MPL/Alum, VC2 was somewhat more effective especially as it relates to neural tissue infection. VC2 was not effective as a therapeutic vaccine.


CONCLUSION
The live attenuated prophylactic HSV vaccine, VC2, was effective in the guinea pig model of genital HSV-2. Its decreased ability to infect neural tissues provides advantages over other live attenuated vaccines.
['Bernstein|David I|DI|', 'Pullum|Derek A|DA|', 'Cardin|Rhonda D|RD|', 'Bravo|Fernando J|FJ|', 'Dixon|David A|DA|', 'Kousoulas|Konstantin G|KG|']
D000276:Adjuvants, Immunologic D000818:Animals D000914:Antibodies, Viral D004195:Disease Models, Animal D005260:Female D006168:Guinea Pigs D006558:Herpes Genitalis D022301:Herpes Simplex Virus Vaccines D018259:Herpesvirus 1, Human D018258:Herpesvirus 2, Human D014611:Vaccination D014613:Vaccines, Attenuated D014621:Vagina D014759:Viral Envelope Proteins D017201:Virus Shedding
Vaccine Guinea pigs Genital herpes Live attenuated vaccine Herpes simplex virus