Nesburn AB, et al

Nesburn AB, et al. 1998. antibodies recognized an Salmeterol Xinafoate average of 6 ORFs per seropositive individual; (ii) the antibody responses to HSV antigens were diverse among HSV-1- and HSV-2-seropositive individuals; (iii) panels of 21 and 30 immunodominant antigens (ID-Ags) were identified from the HSV-1 and HSV-2 ORFomes, respectively, as being highly and frequently recognized by serum antibodies from Salmeterol Xinafoate seropositive individuals; and (iv) interestingly, four HSV-1 and HSV-2 cross-reactive asymptomatic ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients but not by sera from 10 of 10 symptomatic patients ( 0.001). In contrast, sera from symptomatic patients preferentially recognized the US10 ID-S-Ag ( 0.001). We have identified previously unreported immunodominant HSV antigens, among which were 4 ID-A-Ags and 1 ID-S-Ag. These newly identified ID-A-Ags could lead to the development of an efficient asymptomatic vaccine against ocular, orofacial, and genital herpes. INTRODUCTION Herpes simplex virus Salmeterol Xinafoate 1 (HSV-1) and HSV-2 are infectious pathogens that cause serious diseases at every stage of life, from fatal disseminated disease in newborns to cold sores, genital ulcerations, eye disease, and fatal encephalitis in adults (14, 15, 18, 82, 83). HSV-1 infects 60% of the U.S. population, who develop painful recurrent orolabial infections, causing a significant cumulative health care burden (37). For example, infection of the brain and eyes can lead to irreversible brain damage and blindness (37). Over 400,000 adults in the United States have a history of recurrent ocular disease capable of causing a loss of vision (62, 63, 65, 67, 68, 83). Virtually all herpetic orolabial disease is usually caused by HSV-1 (42). HSV-1 contamination is responsible for approximately 50% of clinical first episodes of genital herpes in the United States. The geographic distribution of HSV-1 is usually worldwide, with contamination occurring in both developed and underdeveloped countries. The virus is usually transmitted from infected to susceptible individuals during close personal contact only. There is no seasonal variation in the incidence of infection. HSV-1 contamination is usually rarely fatal and establishes latency in the trigeminal ganglia after primary contamination. Over one-third of the world’s population has recurrent HSV-1 infections, and hence, the probability of transmitting HSV-1 is usually during the episodes of productive contamination and not during latent contamination. As such, recurrent herpes labialis is the largest reservoir of HSV-1 infections in the community. Recurrent genital herpes contamination (primarily by HSV-2) also leads to an immunopathological response that develops into genital ulcerations and scarring (8, 61). The global prevalences of HSV-2-seropositive individuals of 15 years of age and older are estimated to be at least 45 million within the United States (24, 84) and well over 530 million worldwide, with a greater frequency of contamination in women (53). The shedding of reactivated HSV-1 is usually estimated to occur at rates of 3 to 28% in adults who harbor latent HSV-1 in their sensory neurons (44, 78C80). However, the vast majority of these individuals do not experience Rabbit polyclonal to DFFA recurrent herpetic disease and are designated asymptomatic patients (32, 52, 80). In contrast, for some individuals (symptomatic patients), the reactivation of latent virus leads to the induction of ineffective or symptomatic HSV-specific CD4+ and CD8+ T cells (25, 32, 80). While some people have frequent recurrences of herpes disease (i.e., symptomatic patients, with 1 to 5 episodes of recurrent disease/year), others have Salmeterol Xinafoate less frequent recurrent disease to no history of recurrent disease (i.e., asymptomatic patients, with 0 to 1 1 episodes of recurrent disease/year). Interestingly, the difference between the symptomatic and asymptomatic groups is not a result of how often the latent herpesvirus reactivates, as both groups shed the virus at similar rates Salmeterol Xinafoate (75, 80). Instead, the difference is very likely related to variations in the number and nature of HSV antigens (Ags) that are targeted. In animal models, HSV antigens have been reported (i) to be protective against the disease.