COREY LAB

Welcome to the Corey Lab

The Corey Lab investigates the underlying mechanisms between herpes simplex virus pathogenesis and the host immune response. Specifically, the associations between HSV-2 disease severity and the quantity, quality and diversity of tissue resident memory CD8+ T cells persisting after HSV-2 reactivation in humans. 


Herpes Simplex Virus Type-2 (HSV-2)

Herpes simplex virus type-2 (HSV-2) is the number one cause of genital ulcer disease, with increasing prevalence and medical relevance worldwide. The virus is frequently shed throughout the human genital tract even when symptomatic ulcerations are not present, allowing for silent transmission during coitus and promoting high seroprevalence of HSV-2 globally. Most episodes are asymptomatic, however occasionally episodes coincide with painful genital ulcers. Current antiviral therapies limit the severity and frequency of genital lesions, but do not eliminate episodes of subclinical shedding and as such only partially reduce transmission of HSV-2 to new partners. In countries in which sexually active adults have a high prevalence of HSV-2 infection or in subpopulations such as men who have sex with men, where infection is common, HSV-2 is a significant epidemiological driver of HIV-1 epidemics; HSV-2 infection is associated with a two- to fourfold increase in HIV-1 acquisition. In addition, HSV-2 is reactivated and transmitted more frequently in persons co-infected with HIV-1 and HSV-2 than in HIV-1 negative persons. The biological underpinnings behind this co-epidemic are not fully understood, despite having been recognized for over 2 decades. Developing an effective HSV-2 vaccine has received increasing attention from a public health perspective. However, success has not been achieved, largely due to the lack of comprehension of critical immune responses required to prevent HSV-2 acquisition and reactivation. 

HSV-2 global prevalence

To date, the HSV vaccine field has largely focused on strategies that elicit antibody responses, and little attention has been paid to defining the role of T cell mediated immunity, especially mucosal CD8+ T cell responses. The difficulty in developing an effective HSV vaccine underscores our limited understanding of HSV-2 immunology in humans, especially roles the mucosal immune system play in preventing infection and reactivation.


Clinical and virological studies have shown that more than 80% of herpes reactivations occur in the absence of apparent symptoms and are short in duration (lasting only 6 to 12 hours). Moreover, many HSV seropositive people have never experienced acute clinical disease. These clinical evidences indicate that a rapid and effective clearance mechanism present at peripheral mucosal surface. Understanding mechanisms of immune cell activation, regulation and function in genital skin and mucosa, the site of HSV-2 acquisition and reactivation and the battlefield of peripheral immune system, will provide critical insights for the development of a successful HSV-2 vaccine.

 

The laboratory and clinical based programs involve collaborations with VIDD’s Drs. Jia Zhu, Christine Johnston, David Koelle, Josh Schiffer, Amalia Magaret and Anna Wald.