Despite the high global prevalence of herpes simplex virus (HSV) infection, a cure remains elusive. Approximately 67% of the global population has HSV type 1 (HSV-1), which is transmitted through oral contact, while 13% has HSV type 2 (HSV-2), a sexually-transmitted infection that increases the risk of acquiring and transmitting human immunodeficiency virus (HIV) . Effective HSV vaccines are urgently needed to help decrease HIV incidence, as well as prevent neonatal herpes, which, although rare, can lead to neurological disability or death .
The development of effective HSV vaccines is largely hindered by our poor understanding of the host and viral determinants of HSV manifestation in humans, as well as the early kinetics of the immune response [2, 3]. Although murine HSV models are useful for studies of basic immunology, they do not mimic primary or recurrent infection in humans; as a result, vaccine candidates that have shown promising results in animal studies have failed in clinical trials . Skin biopsies from HSV-infected individuals have also provided valuable immunological insights, but it is difficult to access HSV-affected skin on a large scale . Therefore, alternative preclinical platforms for understanding HSV pathogenesis in humans are needed, such as organs-on-a-chip.
Organs-on-a-chip are miniature tissues grown in vitro that can model human physiology and disease, and further drug development by addressing the limitations of cell and animal models . These platforms combine the benefits of both models by culturing human cells in tissue-specific settings that recapitulate the molecular, structural, and physical cues that are found in vivo for an organ system . Consequently, organs-on-a-chip are attractive alternatives for bridging the translational gap between preclinical and clinical stages in vaccine development, particularly for HSV. Sun et al. recently published an article in Nature Communications describing the development of a skin-on-chip platform for modeling HSV infection, as well as evaluating immune responses and antiviral drug efficacy, which we review in this blog post .