About this Research Topic
Incurable ulcerative disease caused by herpes simplex virus (HSV) type 1 and 2 affects more than 3.7 billion and 500 million people worldwide, respectively. Genital HSV-2 infection increases the risk of other sexually transmitted diseases (STDs) including bacterial vaginosis, Zika virus, and most importantly human immunodeficiency virus (HIV), for which risk of acquisition is up to 9-fold higher in persons with genital herpes. Modeling predicts that an HSV-2 vaccine with even 50% efficacy could reduce the incidence of HIV by an astounding 57.4% in the next 40 years. Neonatal herpes infection, one of the most devastating consequences of genital herpes, can occur when genital HSV-1 or 2 is acquired by a birthing parent in the late third trimester and transmitted to the neonate at the time of vaginal delivery. Neonatal herpes is associated with significant neurologic morbidity and mortality. The annual medical cost of herpes infection is estimated to be about $1 billion in the United States and $29 billion in low- and middle-income countries.
During the natural life cycle of HSV in the human host, the virus infects epithelial cells in the genital or oral mucosa, accesses sensory nerve endings, and thereby establishes latency in dorsal root, sacral, and autonomic ganglia. Early after infection, nearly all persons can be shown to have subclinical HSV-2 DNA detectable by PCR on swabs of affected skin, and a substantial percentage experience recurrent symptomatic reactivation during the first year of the disease. During viral reactivation, viral particles are released from nerve endings and reinfect epithelial cells. These sites are the major battlefield between host and virus during the chronic phase. Recurrent viral exposure triggers local residency of unique CD8αα T cells in the dermal-epidermal junction (DEJ) and persistence of CD4+ T cells. The clearance and subsequent control of the virus in tissue is currently believed to depend on these resident memory T cells.
Neutralizing antibodies are the main correlate of protection for most currently licensed vaccines for infectious pathogens. However, failure of multiple candidate vaccines in clinical trials to induce protection from HSV acquisition or recurrence represent one of the greatest enigmas of the field – the lack of correlation between neutralizing antibody titers and protection from infection and disease. The current understanding that control of symptomatic viral reactivation occurs locally at sites of viral release is focused on the role of T cells in containment of viral replication during or prior to a symptomatic outbreak. However, clinical observations as well as experimental and mathematical models present contradictory evidence indicating the contribution of humoral responses in effective viral control. In absence of clearly defined correlates of protection, it is safe to say that both cellular and humoral immune responses likely play important roles.
In this Research Topic, we will explore recent advances in both humoral and cellular immunity to HSV to gain new insights toward the future development of efficacious preventative and immunotherapeutic herpes vaccines. We are in an exciting time in HSV vaccine science, with multiple active clinical trials based in novel technologies, as well as novel computational and translational approaches to study the immune repertoire.
We are interested in Original Research, Review/Mini Review, Opinion, Case Report, and Clinical Trial articles focusing on, but not limited to, the following areas:
• Human and pre-clinical vaccine trials and passive immunization studies
• HSV pathogenesis and HSV immune epitopes
• Translational research in HSV acquisition and transmission, asymptomatic shedding, and/or clinical disease
• Maternal-fetal transfer of HSV-specific antibodies and immune cells
• History and future of HSV vaccine efforts
• Investigations into adaptive immune responses in unique patient populations or with unique presentations of HSV disease
During the natural life cycle of HSV in the human host, the virus infects epithelial cells in the genital or oral mucosa, accesses sensory nerve endings, and thereby establishes latency in dorsal root, sacral, and autonomic ganglia. Early after infection, nearly all persons can be shown to have subclinical HSV-2 DNA detectable by PCR on swabs of affected skin, and a substantial percentage experience recurrent symptomatic reactivation during the first year of the disease. During viral reactivation, viral particles are released from nerve endings and reinfect epithelial cells. These sites are the major battlefield between host and virus during the chronic phase. Recurrent viral exposure triggers local residency of unique CD8αα T cells in the dermal-epidermal junction (DEJ) and persistence of CD4+ T cells. The clearance and subsequent control of the virus in tissue is currently believed to depend on these resident memory T cells.
Neutralizing antibodies are the main correlate of protection for most currently licensed vaccines for infectious pathogens. However, failure of multiple candidate vaccines in clinical trials to induce protection from HSV acquisition or recurrence represent one of the greatest enigmas of the field – the lack of correlation between neutralizing antibody titers and protection from infection and disease. The current understanding that control of symptomatic viral reactivation occurs locally at sites of viral release is focused on the role of T cells in containment of viral replication during or prior to a symptomatic outbreak. However, clinical observations as well as experimental and mathematical models present contradictory evidence indicating the contribution of humoral responses in effective viral control. In absence of clearly defined correlates of protection, it is safe to say that both cellular and humoral immune responses likely play important roles.
In this Research Topic, we will explore recent advances in both humoral and cellular immunity to HSV to gain new insights toward the future development of efficacious preventative and immunotherapeutic herpes vaccines. We are in an exciting time in HSV vaccine science, with multiple active clinical trials based in novel technologies, as well as novel computational and translational approaches to study the immune repertoire.
We are interested in Original Research, Review/Mini Review, Opinion, Case Report, and Clinical Trial articles focusing on, but not limited to, the following areas:
• Human and pre-clinical vaccine trials and passive immunization studies
• HSV pathogenesis and HSV immune epitopes
• Translational research in HSV acquisition and transmission, asymptomatic shedding, and/or clinical disease
• Maternal-fetal transfer of HSV-specific antibodies and immune cells
• History and future of HSV vaccine efforts
• Investigations into adaptive immune responses in unique patient populations or with unique presentations of HSV disease
Keywords: Herpes simplex virus, HSV, sexually transmitted diseases, STDs, HIV, vaccines, antibodies, cellular immune response, humoral immune response, adaptive immunity, pathogenesis
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