Future of an ‘Asymptomatic‘ T-cell Epitope-Based Therapeutic Herpes Simplex Vaccine

Abstract

Considering the limited success of the recent herpes clinical vaccine trial, new vaccine strategies are needed. Infections with HSV-1 and HSV-2 in the majority of men and women are usually asymptomatic and result in lifelong viral latency in neurons of sensory ganglia. However, in a minority of men and women, spontaneous HSV reactivation can cause recurrent disease (i.e., symptomatic individuals). Our recent findings show that T cells from symptomatic and asymptomatic men and women (i.e., those with and without recurrences, respectively) recognize different herpes epitopes. This finding breaks new ground and opens new doors to assess a new vaccine strategy: mucosal immunization with HSV-1 and HSV-2 epitopes that induce strong in vitro CD4 and CD8 T-cell responses from peripheral blood mononuclear cells derived from asymptomatic men and women (designated here as ‘asymptomatic’ protective epitopes) could boost local and systemic ‘natural’ protective immunity, induced by natural infection. Here we highlight the rationale and the future of our emerging asymptomatic T-cell epitope-based mucosal vaccine strategy to decrease recurrent herpetic disease.

Targeting the Genital Tract Mucosa with a Lipopeptide/Recombinant Adenovirus Prime/Boost Vaccine Induces Potent and Long-Lasting CD8+ T Cell Immunity against Herpes: Importance of MyD88

“…After rectal, vaginal, or penile exposure to HSV-2, the virus replicates in the mucosal epithelial cells that leads eventually to rectal or genital herpes lesions (34). The global prevalence of seropositive individuals, fifteen years and older, is estimated to be at least 60 million within the United States, and well over 540 million worldwide (35, 36) with a greater frequency of infection in women (6). Despite the availability of many intervention strategies, such as sexual behavior education, barrier methods, and the costly guanine nucleoside anti-viral drug therapies (e.g.…”

“…Acyclovir and derivatives), controlling the spread of genital herpes remains a challenge (1, 6, 36). The current medical opinion is that an effective clinical vaccine would constitute the best approach to protect the human population from genital herpes (35, 36). Such a vaccine would likely have the greatest impact in both developed and under-developed regions of the world (35, 36).…”

Prospects and perspectives for development of a vaccine against herpes simplex virus infections

“…Reactivity to gD and gB did not distinguish these groups but similar to the immune-seronegative reactivity, the asymptomatic group was significantly more likely to have responses to early viral proteins (in this case UL30 and UL42, two proteins necessary for viral DNA replication. Another novel approaches to discovery of new T cell epitopes should provide insight into the components of HSV-2 vaccines that are likely to perform successfully in the clinic [63,124-126]. …”

Recent advances in vaccine development for herpes simplex virus types I and II

“…Alternatively, it may also be combined with additional vaccines to potentially generate even stronger protective benefits. 3 In any case, the field still needs innovative ways to overcome the challenges posed by HSV to traditional vaccines strategies.…”

“…3,4 The lifelong HSV infection is usually acquired through physical contacts, affecting the epithelial cells of oral and genital tissues. 5 The infected cells are normally non-keratinized epithelial cells when the infection is oral or vaginal and keratinized on other body tissues.…”