One of the troubles in determining the persistence of antibodies after HEV contamination has been the controversy over the accuracy of several available diagnostic assessments [21, 34, 35]; however, only the well-validated, highly sensitive and specific Wantai assay was used to measure anti-HEV IgG in this study. loss was more common among those naturally infected compared with those vaccinated. However, none of the characteristics examined were strongly associated with antibody loss, suggesting that factors not yet identified may play a more important role in antibody loss. Long-term postvaccination antibody persistence is currently unknown and will be an important consideration in the development of guidelines for the use of the highly efficacious HEV vaccine. ClinicalTrials.gov registration.? “type”:”clinical-trial”,”attrs”:”text”:”NCT01014845″,”term_id”:”NCT01014845″NCT01014845. Keywords: antibody persistence, epidemiology, hepatitis E vaccine, hepatitis E computer virus Hepatitis E computer virus (HEV) causes approximately 20 million infections every year in developing countries. HEV usually causes acute hepatitis and is generally self-limiting, but can be very severe in pregnant women and immunocompromised patients [1C4]. In China, HEV is quite common, with seroprevalence estimates around 17% [5]. At least 9 epidemics of hepatitis E (HE) have been documented in China [6, 7], the largest of which occurred in 1986, with 122 000 cases reported and an overall case fatality rate of 0.87% [8]. Even though large epidemics of HEV have not been documented in China since the 1986 outbreak, HEV is an important cause of sporadic hepatitis and is estimated to cause about 20% of acute hepatitis cases [9]. In 2010 2010, a large phase III trial of almost 100 000 participants was completed in Jiangsu Province, China, of a recombinant, subunit hepatitis E vaccine, HEV 239 [10]. This trial found the vaccine efficacy to be 100.0% (95% confidence interval [CI], 72.1%C100.0%) against clinical HE when all 3 doses were given. It was also found to be safe and well tolerated [10]. In December 2011, the HEV 239 vaccine, renamed Hecolin, was licensed by Chinas State Food and Drug Administration, with production beginning in 2012 [11]. One of the major unanswered questions about HEV epidemiology is the persistence of antibodies, both after natural contamination and after vaccination. Based on the paradigm established by other comparable enteric pathogens, antibodies to HEV after an infectious episode were thought to be long lasting; however, a paucity of data exists to empirically support this assumption [12, 13]. The issue of antibody persistence has become of increasing importance due to mounting evidence of dramatically waning or absent antibody concentrations shortly after contamination or vaccination. A number of studies have suggested that individuals can drop detectable antibodies to HEV, or sero-revert. In China, this phenomenon of sero-reversion has been observed in several cohorts. A large population-based study followed healthy, seropositive individuals for 1 BMS-509744 year, during which time 1.4% of individuals experienced HEV sero-reversion [14]. Another large study found that 4.9% of seropositive participants had lost detectable antibodies after 2 years [15]. Antibody persistence after HEV vaccination has not been well characterized yet, due to the recent licensure of the vaccine. Follow-up of the vaccine trial participants suggests that vaccination provides protection against clinical HE, with 60 BMS-509744 cases of HE identified 4.5 years after the trial concluded, 53 in the placebo group and only 7 in the experimental group [16]. During the phase II trial of HEV 239, the anti-HEV titers decreased by 76% only 6 months after the third dose of vaccine [17]. In a more recent follow-up of participants in the phase III HEV 239 vaccine trail, 76% of participants had detectable antibodies after 5 years [18]. Mathematical models of this data suggested that at least 50% of the participants would still have detectable antibodies anywhere from 8 to >30 years Rabbit Polyclonal to Cytochrome P450 1A1/2 after vaccination, depending on the model used [18]. These studies suggest that in certain contexts, antibodies likely persist for a few years after exposure, but can also wane dramatically and, in some instances, become nondetectable. Whether this results in a renewed susceptibility to contamination, or hepatitis E illness, is usually unclear and deserves further study, given the implications for the control of this important pathogen. We examined risk factors associated with the persistence of antibodies after HEV contamination and vaccination in a subset of individuals enrolled in the large phase III HEV vaccine trial in Dongtai, China. This is one of the first studies to explore the characteristics associated with BMS-509744 long-term antibody persistence after HEV exposure in asymptomatic, naturally infected (with a known.