Anti-Epstein-Barr Virus BNLF2b for Mass Screening for Nasopharyngeal Cancer.

Background: Population screening of asymptomatic persons with Epstein-Barr virus (EBV) DNA or antibodies has improved the diagnosis of nasopharyngeal carcinoma and survival among affected persons. However, the positive predictive value of current screening strategies is unsatisfactory even in areas where nasopharyngeal carcinoma is endemic.

Methods: We designed a peptide library representing highly ranked B-cell epitopes of EBV coding sequences to identify novel serologic biomarkers for nasopharyngeal carcinoma.

Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody.

Hepatitis E virus (HEV), a non-enveloped, positive-sense, single-stranded RNA virus, is a major cause of enteric hepatitis. Classified into the family Hepeviridae, HEV comprises four genotypes (genotypes 1-4), which belong to a single serotype. We describe a monoclonal antibody (mAb), 8G12, which equally recognizes all four genotypes of HEV, with ∼ 2.

Long-term efficacy of a hepatitis E vaccine.

Background: Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined.

Methods: In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants).

Protective immunity against HEV.

Rural community of Dongtai City in eastern China is endemic for hepatitis E virus (HEV), with the zoonotic genotype 4 virus predominating. The virus appears to be widely distributed in environment at generally low levels, such that infection is common, but >97% of which are asymptomatic and provoke a modest antibody response. Naturally acquired immunity affords 75% protection against infection, prevents disease caused by primary infection and alleviates severity of the disease caused by the residual infection that had evaded host immune surveillance.

Epidemiology of zoonotic hepatitis E: a community-based surveillance study in a rural population in China.

Background: Hepatitis E is caused by two viral genotype groups: human types and zoonotic types. Current understanding of the epidemiology of the zoonotic hepatitis E disease is founded largely on hospital-based studies.

Methods: The epidemiology of hepatitis E was investigated in a community-based surveillance study conducted over one year in a rural city in eastern China with a registered population of 400,162.

Immunogenicity and safety of hepatitis E vaccine in healthy hepatitis B surface antigen positive adults.

A recombinant hepatitis E vaccine, Hecolin, has been proven safe and effective in healthy adults. As hepatitis B surface antigen (HBsAg) positive individuals have a higher risk of poor prognosis after super-infection with hepatitis E virus (HEV), the safety and immunogenicity of Hecolin in this population should be assessed. The present study is an extending analysis of data from a large randomized controlled clinical trial of Hecolin.

Antigenic determinants of hepatitis E virus and vaccine-induced immunogenicity and efficacy.

There is emerging evidence for an under-recognized hepatitis E virus (HEV) as a human pathogen. Among different reasons for this neglect are the unsatisfactory performance and under-utilization of commercial HEV diagnostic kits; for instance, the number of anti-HEV IgM kits marketed in China is about one-fifth of that of hepatitis A kits. Over the last two decades, substantial progress has been achieved in furthering our knowledge on the HEV-specific immune responses, antigenic features of HEV virions, and development of serological assays and more recently prophylactic vaccines.

Hepatitis E vaccine development: a 14 year odyssey.

The first prophylactic vaccine, Hecolin®, against hepatitis E virus (HEV) infection and the HEV associated disease was approved by China's State Food and Drug Administration (SFDA) in December 2011. Key milestones during the 14-year HEV vaccine development are summarized in this commentary.  After years of innovative research the recombinant virus-like particle (VLP) based antigen with virion-like epitopes was successfully produced in E.

Hepatitis E virus: neutralizing sites, diagnosis, and protective immunity.

There have been increased attentions on HEV and its associated diseases in recent years as a result of an increased number of reports on autochthonous patients from many developed countries. Vaccine development and better disease management are expected from protective immunity with increased knowledge on the pathogenesis and virology of HEV. This review summarizes the current understanding of the HEV virology, the key neutralization sites (epitopes) on the surface of the viral capsid, the host humoral immune responses for HEV infection, and the protective immunity conferred by natural infection and vaccination.

Mimotope ELISA for detection of broad spectrum antibody against avian H5N1 influenza virus.

Background: We have raised a panel of broad spectrum neutralizing monoclonal antibodies against the highly pathogenic H5N1 avian influenza virus, which neutralize the infectivity of, and afford protection against infection by, most of the major genetic groups of the virus evolved since 1997. Peptide mimics reactive with one of these broad spectrum H5N1 neutralizing antibodies, 8H5, were identified from random phage display libraries.

Method: The amino acid residues of the most reactive 12mer peptide, p125 (DTPLTTAALRLV), were randomly substituted to improve its mimicry of the natural 8H5 epitope.

Detection of Stage I nasopharyngeal carcinoma by serologic screening and clinical examination.

In a prospective study, 42 048 adults residing in Zhongshan City, Guangdong, China, were followed for 16 years, and 171 of them developed nasopharyngeal carcinoma (NPC). Although Epstein-Barr virus (EBV) antibody levels of the cohort fluctuated, the antibody levels of 93% of the patients with NPC were raised and maintained at high levels for up to 10 years prior to diagnosis. This suggests that the serologic window affords an opportunity to monitor tumor progression during the preclinical stage of NPC development, facilitating early NPC detection.

Profile of acute infectious markers in sporadic hepatitis E.

Laboratory diagnosis of acute infection of hepatitis E virus (HEV) is commonly based on the detection of HEV RNA, IgM and/or rising IgG levels. However, the profile of these markers when the patients present have not been well determined. To clarify the extent of misdiagnosed sporadic hepatitis E in the initial laboratory detection, serial sera of 271 sporadic acute hepatitis cases were collected, detected and the dynamics of each acute marker during the illness course were analyzed.

Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial.

Background: Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial.

Methods: Healthy adults aged 16-65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 microg of purified recombinant hepatitis E antigen adsorbed to 0.

Performance of detecting IgM antibodies against enterovirus 71 for early diagnosis.

Enterovirus 71 (EV71) infection is more likely to induce severe complications and mortality than other enteroviruses. Methods for detection of IgM antibody against EV71 had been established for years, however, the performance of the methods in the very early diagnosis of EV71 infection had not been fully evaluated, which is especially meaningful because of the short incubation period of EV71 infection. In this report, the performance of an IgM anti-EV71 assay was evaluated using acute sera collected from 165 EV71 infected patients, 165 patients infected with other enteroviruses, and more than 2,000 sera from healthy children or children with other infected diseases.

Prevalence of hepatitis E virus in Chinese blood donors.

A point prevalence study of hepatitis E virus (HEV) in Chinese blood donors was conducted, and the prevalences of antibodies against HEV immunoglobulin G (IgG) and IgM among Chinese blood donors were 32.60% and 0.94%, respectively.

Randomized-controlled phase II clinical trial of a bacterially expressed recombinant hepatitis E vaccine.

The candidate recombinant hepatitis E vaccine, HEV 239, protect monkeys against infection by hepatitis E virus (HEV). The safety and immunogenicity of the vaccine for humans was assessed in a randomized controlled phase II clinical trial. The study was conducted in an endemic area of southern China and consisted of a dose scheduling, involving 457 adults and a dose escalation component involving 155 high school students.

Broad cross-protection against H5N1 avian influenza virus infection by means of monoclonal antibodies that map to conserved viral epitopes.

Background: Passive immunization with human H5 antisera or H5-specific monoclonal antibodies (MAbs) has potential as an effective treatment for acute H5N1 influenza virus infection, but its efficacy against antigenically diverse H5N1 viruses is unconfirmed.

Methods: Cross-protection against antigenically diverse H5N1 strains with H5-specific MAbs, generated by successive immunization of antigenically distinct strains, was evaluated in mice.

Results: A panel of 52 broadly cross-reactive H5 specific MAbs were generated and characterized.

Peptide mimics of a conserved H5N1 avian influenza virus neutralization site.

A panel of 52 murine monoclonal antibodies was found to recognize antigenic determinants that had been conserved among all major genetic subgroups of the H5N1 avian influenza virus prevalent since 1997. We screened a phage display library for peptides recognized by one such antibody (8H5). We analysed the specificity of 8H5 for reactive peptides presented as fusion proteins of HBc (hepatitis B core protein) and HEV (hepatitis E virus) structural protein, p239.

Evaluation of two anti-hepatitis E virus IgM kits.

Objective: To evaluate two commercial anti-hepatitis E virus (HEV) IgM kits used for differential diagnosis of acute enteric viral hepatitis.

Methods: The kit for IgM capture assay, was produced with a recombinant HEV structural protein protecting primates against experimental infection by different HEV genotypes, while the other kit for indirect ELISA was produced with recombinant structural proteins from different HEV genotypes. The serum specimens were taken from 241 cases with a confirmed or presumptive diagnosis of hepatitis A and 74 cases with a confirmed or presumptive diagnosis of hepatitis E.

Putative receptor-binding sites of hepatitis E virus.

A truncated structural protein of hepatitis E virus (HEV), p239, occurs as 23 nm particles consisting of partial homodimers. As the latter resemble the HEV capsomere structurally and antigenically, it was postulated that the recombinant protein may serve as a probe for the HEV receptor. This hypothesis was supported by findings that purified p239 bound and penetrated different cell lines that are susceptible to HEV, and inhibited HEV infection of these cells.

Difference of T cell and B cell activation in two homologous proteins with similar antigenicity but great distinct immunogenicity.

The candidate particulate hepatitis E vaccine, HEV 239, has been shown to be an efficacious vaccine in primates, and clinical study to date shows it to be safe and immunogenic for humans. The antigenicity of HEV 239 is virtually identical to its N-terminal 26 amino acids truncated protein, E2, which is not particulate but soluble. However, HEV 239 is over 200 times more immunogenic than E2.

Seroprevalence of hepatitis E virus infection, rural southern People's Republic of China.

Genotype 4 hepatitis E virus (HEV) is the dominant cause of hepatitis E in the People's Republic of China; swine are the principal reservoir. Our study was conducted in 8 rural communities of southern China, where families keep pigs near their homes. Phylogenetic analysis showed that 23 of 24 concurrent virus isolates from this region are genotype 4 strains.

Complementary activation of peripheral natural killer cell immunity in nasopharyngeal carcinoma.

NK cells and alphabeta- and gammadelta-CTL play important roles in cellular immunity against tumors. We previously demonstrated that NPC patients have a quantitative and qualitative deficit in gammadelta-CTL and EBV-specific alphabeta-CTL when compared to normal subjects and NPC long-term survivors. In this study we report further observations of a complementary activation of peripheral NK cells in NPC patients.

Swine as a principal reservoir of hepatitis E virus that infects humans in eastern China.

Background And Methods: Genotype IV hepatitis E virus (HEV) has been isolated from humans and swine. To study the relationship between the human and swine reservoirs, we estimated their respective viral burden, analyzed the genetic makeup of the virus populations, and assessed the risk of infection associated with swine farming.

Results: In 2 swine-farming districts of eastern China, 9.

Epstein-Barr virus serology in early detection and screening of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a common cancer among Chinese, especially Southern Chinese; except for a few other ethnic groups with moderate incidence, it is otherwise a rare cancer in the world. NPC has a male dominance of about 3:1 and mainly afflicts people in mid-life. There is now compelling evidences to suggest that Epstein-Barr virus (EBV), a category I human tumor virus defined by UICC (International Agency for Research on Cancer) in 1997, is a causal agent of NPC and is most likely to be involved in the multi-step and multi-factorial development of NPC.