Abstract
One promising approach for a herpes simplex virus vaccine uses a vaccine to prime and a chemoattractant to pull immune cells into the genital tract. We evaluated subunit vaccines (prime) and imiquimod (pull) in the guinea pig (gp) model of recurrent Herpes simplex virus type-2 (HSV-2). Following vaginal HSV-2 infection, gps were vaccinated with various combination of glycoproteins and adjuvant with or without subcutaneous or local applications of imiquimod after infection. Animals were examined daily for recurrent lesions and vaginal swabs collected for recurrent shedding. Although both the vaccines alone and imiquimod alone reduced recurrent HSV disease, the combination of local imiquimod and vaccine (Prime and Pull) was the most effective. In the first study, immunization with the trivalent vaccine alone or imiquimod alone decreased recurrent disease. However, the largest decrease was with the combination of vaccine and local imiquimod (P < 0.001 vs. placebo or vaccine alone). No effect on recurrent shedding was observed. In the second study, recurrent disease scores were similar in the PBS control group and the trivalent-immunized group treated with subcutaneous imiquimod however, significant reductions with glycoprotein vaccines and local imiquimod (p < 0.01 vs. placebo) were noted. The number of qPCR-positive recurrent swabs, ranged from 5 to 11% in the vaccinated+local imiquimod groups compared 29% in the PBS control group (P < 0.05). No recurrent swab samples from vaccinated groups were culture positive. We conclude that the strategy of prime (subunit HSV vaccine) and topical pull (intravaginal/topical imiquimod) decreased recurrent HSV more effectively than vaccine alone.
Highlights
Genital HSV infections are recognized to increase the acquisition of HIV and result in increased shedding of HIV.[7]
Available antiviral therapies are somewhat effective in the treatment of recurrent HSV disease; shortening lesion duration and decreasing viral shedding but are only effective during the time of drug administration.[8,9]
The therapeutic potential of immunotherapy was not demonstrated conclusively until 1988, when Stanberry et al.[11] were able to show, using the guinea pig model of genital herpes, that a vaccine could reduce the number of genital herpes recurrences
Summary
Herpes simplex virus type 2 (HSV-2) is estimated to infect 417 million people globally, with 19.2 million new infections annually.[1]. The therapeutic potential of immunotherapy was not demonstrated conclusively until 1988, when Stanberry et al.[11] were able to show, using the guinea pig model of genital herpes, that a vaccine could reduce the number of genital herpes recurrences In these trials, vaccination reduced recurrent lesions or recurrent shedding rates by ~ 50%. In this manuscript we extend the application to therapeutic vaccines and show that the frequency of recurrent disease and recurrent vaginal shedding was reduced most effectively by the combination of prime (glycoprotein vaccine) and pull (vaginal imiquimod)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call