Successful application of prime and pull strategy for a therapeutic HSV vaccine

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\u2009<\u20090.001 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\u2009<\u20090.01 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\u2009<\u20090.05). 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.Herpes simplex virus: prime and pull vaccination“Prime and pull” vaccination strategies involve an initial vaccination followed by the local application of a stimulant such as chemokines to recruit immune cells to infection target areas such as the mucosa. David Bernstein and colleagues investigate the efficacy of a prime and pull approach in a guinea pig model of recurrent genital Herpes simplex virus 2 (HSV-2) infection. Animals were vaccinated with HSV-2 glycoproteins in adjuvant with or without subcutaneous or topical (vaginal) exposure to the immune stimulant imiquimod to act as the “pull”. Animals with topical imiquimod show superior control of HSV-2 infection and improved recruitment of CD8+ T cells to the vaginal epithelium. Topical application of imiquimod demonstrates better control than subcutaneous imiquimod suggesting that “pulling” might be a useful approach in HSV vaccination.