Abstract
A majority of the world’s population is infected with HSV-1, highlighting the need for vaccines that are effective in HSV-1-seropositive hosts. We established a superinfection model by infecting mice intranasally with a sublethal dose of HSV-1, which results in high rates of seropositive, latently infected mice susceptible to HSV-2 superinfection. Sublethal HSV-1 induced a predominantly neutralizing antibody response. Vaccination of HSV-1-seropositive mice with recombinant adjuvanted glycoprotein D (rgD-2) failed to significantly boost HSV total or neutralizing antibody responses and provided no significant increased protection against HSV-2 superinfection compared to control-vaccinated HSV-1-seropositive mice. In contrast, immunization with a single-cycle virus deleted in gD (ΔgD-2) significantly boosted total HSV-specific antibody titers and elicited new antibody-dependent cell-mediated cytotoxicity responses, providing complete protection from death following HSV-2 superinfection. This model recapitulates clinical responses to natural infection and the rgD-2 vaccine trial outcomes and suggests that ΔgD-2 may prove protective in HSV-1-seropositive hosts.
Highlights
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are prevalent infections causing recurrent oral, ocular and genital disease as well as sporadic encephalitis[1,2]
In the U.S, HSV-1 has emerged as the more common cause of genital herpes, but in Africa, HSV-2 continues to dominate and numerous epidemiologic studies have shown that genital HSV-2 infection contributes more than any other biological factor to the HIV epidemic[2,3,4,5,6,7]
A subunit vaccine comprised of recombinant HSV-2 glycoprotein D combined with alum and monophosphoryl lipid A (MPL) was evaluated in three different Phase 3 clinical trials
Summary
Herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are prevalent infections causing recurrent oral, ocular and genital disease as well as sporadic encephalitis[1,2]. A vaccine for HSV-2 prevention must be immunogenic and protective in HSV-1 seropositive individuals. Several prophylactic HSV-vaccine candidates have been evaluated in clinical trials with overall disappointing results. A subunit vaccine comprised of recombinant HSV-2 glycoprotein D combined with alum (aluminum and magnesium hydroxide) and monophosphoryl lipid A (MPL) (gD-AS04) was evaluated in three different Phase 3 clinical trials. The first two studies were conducted in serodiscordant couples and included HSV-1seropositive individuals in the second consort[8]. The vaccine showed no efficacy in HSV-1-seropositive men or women, but provided some protection against HSV-2 acquisition in doubly (HSV-1 and HSV-2)-seronegative women, but not men[8]. In a subsequent field study in which only doubly-seronegative women were enrolled, there was no protection against genital HSV-2 but modest protection against genital HSV-19
Sign-in/Register to view highlights & summary 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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
