Vaccination with HepB-CpG vaccine in individuals undergoing immune suppressive drug therapy.

BACKGROUND: Immunosuppressed patients are a targeted group for HBV vaccination but suboptimal antibody responses occur when traditional recombinant vaccines are used. METHODS: We tested an FDA approved immune adjuvanted HBV vaccine (HEPLISAV--B® or HepB-CpG) in medically immune suppressed individuals. HepB-CpG was given to 10 patients taking biologic agents or anti-rejection therapy. Each received vaccine at time 0 and week 4 with a third dose at week 12 if anti-HBs remained less than 10 mIU/mL. RESULTS: Seroprotective anti-HBs developed in 70 % of participants by week 24. Those taking biologic agents responded more rapidly and a third dose was generally needed in those transplanted. By week 24, most taking biologics but only 2 of 6 on anti-rejection treatment had antibody levels exceeding 100 mIU/mL. CONCLUSIONS: Seroprotective anti-HBs developed in 70 % with HepB-CpG. Antibody responses were more rapid in those taking biologic agents but a third dose improved antibody responses in transplanted participants.

Complete genome analysis of hepatitis B virus in Qinghai-Tibet plateau: the geographical distribution, genetic diversity, and co-existence of HBsAg and anti-HBs antibodies.

BACKGROUND: The genetic variation and origin of Hepatitis B Virus (HBV) in Qinghai-Tibet Plateau were poorly studied. The coexistence of HBsAg and anti-HBs has been described as a puzzle and has never been reported in the indigenous population or in recombinant HBV sequences. This study aimed to report geographical distribution, genetic variability and seroepidemiology of HBV in southwest China. METHODS: During 2014-2017, 1263 HBsAg positive serum were identified and 183 complete genome sequences were obtained. Serum samples were collected from community-based populations by a multistage random sampling method. Polymerase chain reaction (PCR) was used to amplify the HBV complete genome sequences. Then recombination, genetic variability, and serological analysis were performed. RESULTS: (1) Of the 1263 HBsAg positive serum samples, there were significant differences between the distribution of seromarkers in Tibet and Qinghai. (2) Of 183 complete genome sequences, there were 130 HBV/CD1 (71.0%), 49 HBV/CD2 (26.8%) and four HBV/C2 isolates (2.2%). Serotype ayw2 (96.1%) was the main serological subtype. (3) Several nucleotide mutations were dramatically different in CD1 and CD2 sequences. Clinical prognosis-related genetic variations such as nucleotide mutation T1762/A1764 (27.93%), A2189C (12.85%), G1613A (8.94%), T1753C (8.38%), T53C (4.47%) T3098C (1.68%) and PreS deletion (2.23%) were detected in CD recombinants. (4) From the inner land of China to the northeast boundary of India, different geographical distributions between CD1 and CD2 were identified. (5) Twenty-seven (2.14%) HBsAg/HBsAb coexistence serum samples were identified. S protein amino acid mutation and PreS deletion were with significant differences between HBsAg/HBsAb coexistence group and control group. CONCLUSIONS: HBV/CD may have a mixed China and South Asia origin. Based on genetic variations, the clinical prognosis of CD recombinant seems more temperate than genotype C strains in China. The HBsAg/HBsAb coexistence is a result of both PreS deletion and aa variation in S protein. Several unique mutations were frequently detected in HBV/CD isolates, which could potentially influence the clinical prognosis.

Persistence of immunity in healthy adults aged ≥ 50 years primed with a hepatitis B vaccine 3 years previously.

Hepatitis B vaccines do not generate protective immune responses in older adults as effectively as they do in children and young adults. Improved formulations of existing vaccines may have the potential to improve this. This study investigated the persistence of serum antibodies against hepatitis B surface antigens (anti-HBs) 3.1-3.5 years following primary vaccination with 3 doses of HBvaxPRO® or Engerix B™ in healthy adults aged ≥ 50 years who were further challenged with 1 dose of recombinant hepatitis B antigen. This was an open-label extension study. Individuals (N = 204) with a mean (standard deviation) age at enrollment of 63.7 (7.0) years receiving HBvaxPRO® or Engerix B™ in a randomized, double-blind primary study were challenged with 1 dose of HBvaxPRO® (10 µg). Anti-HBs were measured pre- and 30 days post-challenge. 45.5% (34.8, 56.4 [95% CI]) of individuals who received HBvaxPRO® in the per protocol set (PPS) had anti-HBs titers ≥ 10 mIU/mL pre-challenge and 85.2% (76.1, 91.9) 1-month post-challenge. In those who received Engerix B™ in the primary vaccination series, the results were 58.8% (48.6, 68.5) and 88.3% (80.5, 93.8), respectively. The challenge dose of HBvaxPRO® was generally well tolerated. Subjects aged ≥ 50 years receiving a challenge dose of HBvaxPRO® demonstrated immune memory against hepatitis B 3 years after a 3-dose primary. The safety profile of this challenge dose of HBvaxPRO® was consistent with the well-established safety profile of the vaccine HBvaxPRO®.

The persistence of anti-HBs antibody and anamnestic response 20 years after primary vaccination with recombinant hepatitis B vaccine at infancy.

Hepatitis B (HB) vaccine induces protective levels of antibody response (anti-HBs≥10 mIU/mL) in 90-99% of vaccinees. The levels of anti-HBs antibody decline after vaccination. The aim of this study was to evaluate the persistence of anti-HBs antibodies and immunologic memory in healthy adults at 20 years after primary vaccination with recombinant HB vaccine. Blood samples were collected from 300 adults at 20 years after primary HB vaccination and their sera were tested for anti-HBs antibody by ELISA technique. A single booster dose of HB vaccine was administered to a total of 138 subjects, whose anti-HBs antibody titer was <10 mIU/mL. The sera of subjects were re-tested for the anti-HBs antibody levels at 4 weeks after booster vaccination. At 20 years after primary vaccination 37.0% of participants had protective levels of antibody with geometric mean titer (GMT) of 55.44±77.01 mIU/mL. After booster vaccination, 97.1% of vaccinees developed protective levels of antibody and the GMT rose from 2.35±6.49 mIU/mL to 176.28±161.78 mIU/mL. 125/138 (90.6%) of re-vaccinated subjects also showed an anamnestic response to booster vaccination. At 20 years after primary vaccination with HB vaccine, low proportion of the subjects had protective levels of antibody. However, the majority of the re-vaccinated subjects developed protective levels of anti-HBs and showed an anamnestic response after booster vaccination. Additional follow-up studies are necessary to determine the duration of immunological memory.

Prevalence of Australia Antigen and Antibody in Pediatric Age Group

Research study of Hepatitis B infection has been much advanced recently and the incidence of the Hepatitis B infection, such as acute viral hepatitis, chronic active hepatitis, chronic persistant hepatitis, acute fulminating hepatitis and carrier states are increasing significantly. The authors evaluated HBsAg and AntiHBs in the child age group and the results are summarized as follows: Of 271 children who were admitted during the period of June 1, 1981 to August 31, 1981, 15(5.9%) were HBsAg positive and 24(8.86%) were antiHBs positive. The highest incidence of HBs Ag among the children was school age group. The highest incidence of AntiHBs was newborn age group. Of 92 children who were living in the orphanage, 12(13.0%) were HBsAg positive and 8 (8.71%) were AntiHBs positive. There was no significant difference in comparison by each room.

Prevalence of Australia Antigen and Antibody in Pediatric Age Group

Research study of Hepatitis B infection has been much advanced recently and the incidence of the Hepatitis B infection, such as acute viral hepatitis, chronic active hepatitis, chronic persistant hepatitis, acute fulminating hepatitis and carrier states are increasing significantly. The authors evaluated HBsAg and AntiHBs in the child age group and the results are summarized as follows: Of 271 children who were admitted during the period of June 1, 1981 to August 31, 1981, 15(5.9%) were HBsAg positive and 24(8.86%) were antiHBs positive. The highest incidence of HBs Ag among the children was school age group. The highest incidence of AntiHBs was newborn age group. Of 92 children who were living in the orphanage, 12(13.0%) were HBsAg positive and 8 (8.71%) were AntiHBs positive. There was no significant difference in comparison by each room.