Recent Progress in Herpes Simplex Virus Immunobiology and Vaccine Research

Abstract

Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) cause prevalent, chronic infections that have serious outcomes in some individuals. Neonatal herpes may occur when the infant traverses the cervix during maternal genital herpes. Genital herpes is a major risk factor for human immunodeficiency virus type 1 transmission. Considerable efforts have been made to design and test vaccines for HSV, focusing on genital infection with HSV-2. Several protein subunit vaccines based on HSV-2 envelope glycoproteins have reached advanced-phase clinical trials. These antigens were chosen because they are the targets of neutralizing-antibody responses and because they elicit cellular immunity. Encouraging results have been reported in studies of treatment of HSV-seronegative women with a vaccine consisting of truncated glycoprotein D of HSV-2 and a novel adjuvant. Because most sexual HSV transmission occurs during asymptomatic shedding, it is important to evaluate the impact of vaccination on HSV-2 infection, clinically apparent genital herpes, and HSV shedding among vaccine recipients who acquire infection. There are several other attractive formats, including subunit vaccines that target cellular immune responses, live attenuated virus strains, and mutant strains that undergo incomplete lytic replication. HSV vaccines have also been evaluated for the immunotherapy of established HSV infection

Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia

“…These complications are most prevalent among immune-compromised individuals. This finding supports the long-held conclusion that the immune system controls viral replication and suppresses viral reactivation (5,6). The association of viral reactivation with immune suppression and the recently observed persistence of T cells and cytokines in latently infected human TG (7,8) strongly suggest a pivotal role of T cells in control of the virus at the site of latency.…”

“…However, it is unclear whether the infiltration and retention of T cells in human TG is antigen-driven and how they may contribute to sustain viral latency. This information is of importance because antiviral treatment suppresses symptomatic ␣-herpesvirus-mediated diseases effectively but does not eradicate the latent viral burden (5,6).…”

Frontline: Induction of apoptosis and modulation of c‐FLIPL and p53 in immature dendritic cells infected with herpes simplex virus

“…Less often, HSV infection can result in lifethreatening encephalitis in otherwise healthy individuals and disseminated infection in immunocompromised persons. At present, HSV vaccines are being explored and new promising treatment modalities have been developed that are based on immunological intervention [2]. To achieve this goal, a detailed understanding of how HSV interacts with components of the immune system is required.…”

Replication-competent herpes simplex vectors: design and applications

“…The concerns surrounding the development of a live viral vaccine for HSV are mainly safety issues revolving around the potential for reactivation from latency, recombination with wt virus, and the oncogenic potential of viral DNA. [8][9][10][11] The first attenuated HSV virus to be constructed and analyzed as a viral vaccine in humans was the NV1020 (formerly R7020) strain. 12,13 This virus, based on HSV-1 strain F, has a portion of the unique short region of the viral genome encoding glycoproteins G, D, I and E, replaced by the homologous region from HSV-2, and possesses one copy of ICP4.…”