Respuesta inmunitaria a la vacuna de la hepatitis B en pacientes hemodializados en Brasil y sus factores asociados / Factors associated with the immune response to hepatitis B vaccine in Brazilian hemodialysis patients

Background:Patients on chronic hemodialysis have a lower immune response to vaccination against hepatitis B virus (HBV) than the general population. Aim: To identify factors that may interfere with immunization against hepatitis B virus (HBV) in Brazilian hemodialysis patients and analyze the evolution of the level of antibodies. Patients and Methods: A retrospective longitudinal study, using records of patients on hemodialysis in the years 2000-2008. Non-responder patients, defined as a level of anti-HBs less than 10 IU/mL, were identified. The effect of social and demographic factors, clinical and laboratory data on the lack of response was evaluated. Logistic regression analysis was used to assess the independent effect of each factor. The difference between initial and final anti-HBs levels (24 months), was also analyzed. Results: Fifty seven percent of patients responded adequately to vaccination. After adjustment with other variables, the only factor associated with immune response was serum ferritin. Responding patients of less than 40 years of age did not have a significant decrease in antibody titers over time. The initial anti-HBs title, influenced the final title. Fifty percent of non-responders achieved serum levels of protection after revaccination. Conclusions: The study showed that ferritin may be a marker of reduced immune response. Patients aged less than 40 years were the only ones who maintained over time their initial anti-HBs levels.

Humoral immune response following hepatitis B vaccine booster dose in children with and without prior immunization.

One hundred and twenty-three children who had received no, incomplete and complete primary hepatitis B vaccination but had negative or very low anti-HBs titer were immunized with a single dose of recombinant hepatitis B vaccine. Blood tests for anti-HBs were obtained at 30 +/- 5 days after the booster immunization. Twelve of 18 (66.7%) children without prior immunization (group 1) seroconverted following the single dose Seroconversion rates in children who had undetectable anti-HBs with incomplete and complete primary immunization (group 2 and 3) were 83.34% and 94.5%, respectively. All children with complete 3- dose vaccination but who had low anti-HBs titer (group 4) also seroconverted. This study confirmed that immunological memory, allowing a protective anamnestic response, lasted at least 8 years in children who had received primary HB immunization with undetectable anti-HBs. Therefore, we conclude that the booster dose after complete vaccination is not necessary in healthy children.

Clinical safety and efficacy of first indigenous recombinant hepatitis B vaccine.

A pilot study was conducted to assess the clinical safety and immunogenicity of an indigenously developed recombinant hepatitis B vaccine (Shanvac B) in 18 healthy adults. 20 microg of vaccine was administered at 0, 1 and 2 months. Protective anti HBs titres developed in 22%, 77% and 100% one month after 1st, 2nd and 3rd dose of vaccination, respectively. The geometric mean titre after the 3rd dose was 1015.29 mIu/ml. The vaccine was well tolerated with minor local and systemic side effects in 28% and 22%, respectively. The indigenously developed recombinant hepatitis B vaccine is safe, well tolerated and highly immunogenic.

Immunogenicity and efficacy of a recombinant DNA hepatitis B vaccine, GenHevac B Pasteur in high risk neonates, school children and healthy adults.

The immunogenicity and the protective efficacy of a recombinant DNA hepatitis B vaccine, GenHevac B Pasteur with or without passive immunization with hepatitis B immunoglobulin (HBIG) in high risk neonates born from HBsAg and HBeAg positive mothers was evaluated. Twenty-six neonates (group A) received HBIG 100 IU intramuscularly at birth plus GenHevac B Pasteur 20 micrograms at birth, 1, 2 and 12 months of age while another 23 neonates (group B) received only GenHevac B Pasteur vaccine. Forty high risk newborns who received no immunization served as control group. It was found that at months 4, 12, 13 and 24 the seroconversion rate in both group A and B were very high in the range of 95-100% with the GMT ranging from 10-160,000 mlU/ml. In the control group of infants, 85% had HBsAg positive at one year of age but it was only 3.8% and 8.7% in vaccinated groups A and B, respectively. The protective efficacy in neonates group A and B were 95.5% and 89.8% at one year, respectively, with no statistically significant difference. In 46 normal school children (group C) and 48 healthy adults (group D) who received the same dose of GenHevac B Pasteur the seroconversion rates at month 4 after receiving 3 doses of vaccination were 97.8% and 83.3% in group C and group D, respectively. At month 12, the seroconversion rate in group C rose to 100% and was significantly higher than the 89.6% of group D.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of immunogenicity of hepatitis B vaccine between low and normal birth weight infants.

A comparative study was conducted to evaluate the immunogenicity of hepatitis B vaccine in low and normal birth weight infants. Hepatitis B vaccine (Hevac B Pasteur) was given to 50 low birth weight infants and 50 controls, matched by sex and date of delivery. The vaccine was given at birth, 1, 2 and 12 months of age. HBsAg and anti-HBs were assessed at birth, 4, 9 and 13 months of age by the micro-ELISA technique. Using the geometric mean titre of anti-HBs and the seroconversion rate as indicators, the immunogenicity of hepatitis B vaccine in low birth weight infants was as good as in normal birth weight infants.

Immune response to hepatitis B vaccine in premature neonates.

The immunogenecity of a recombinant yeast-derived hepatitis B vaccine in 25 premature infants who were born to HBsAg negative mothers was studied. The gestational ages were 28-37 weeks and birth weights were 1300-2000 grams. Seroconversion occurred in 22 infants, the anti HBs titers varied between 50 and 13,470 IU/L (Geometric mean titer = 542 IU/L). Seroconversion rate = 88%. The response did not vary with gestational age, birth weight or illness status.

Immune response to hepatitis B viral antigens in chronic infection & its relationship with liver necrosis.

Markers of hepatitis B virus (HBV) and immune response against them were studied in 18 chronic asymptomatic carriers, 8 patients of the virus induced chronic liver disease (CLD), and 7 patients of chronic alcoholic liver cirrhosis, who were also chronic HBV carriers (CALC). The LMI responses to HBeAg were elevated in HBeAg and/or HBV-DNA positive chronic asymptomatic carriers, (median response 31.5%), along with elevation of serum alanine aminotransferase (sALT) levels (59-150 IU/l). On the other hand the LMI responses to this antigen, in HBeAg and HBV-DNA negative chronic carriers were in the normal range (median response 12%) and their sALT levels were also normal (7-50 IU/l). The CLD and CALC patients did not show any relation between their LMI to HBeAg and sALT levels. In contrast no relation between LMI to HBsAg and sALT levels was observed in any group. The LMI responses to HBsAg in CLD patients were elevated (median response 38%) and the responses of chronic asymptomatic carriers and CALC patients were either in the normal range or poor (median responses, 18 and 7% respectively), irrespective of their sALT levels. These results suggest that T cell responses to both the antigens may be involved in liver cell damage.

Production of anti-HBsAg monoclonal antibodies

The production of monnoclonal antibodies against the HBsAg is reported. Balb/c mice immunized against a commercial vaccine were used. Upon fusion of spleen cells from an animal having a high titer with the SP2/0 myeloma cell line, we obtained 6 stable cell lines, all of the IgG1 subclass. They showed a wide range of specificities against the classical HBsAg subtypes. These monoclonal antibodies can be used as the basis for the development of new methods for the screening and study of the hepatitis B virus

Active pre-exposure immunisation against hepatitis B virus: immunogenicity of hepatitis B vaccine in healthy Thai adults and children.

The immunogenicity of plasma derived hepatitis B vaccine (Hevac B) was studied for active pre-exposure immunisation in 176 healthy volunteer adults and 162 randomised children who had no hepatitis B virus markers. All subjects received three injections of 5 micrograms of hepatitis B vaccine intramuscularly at one month intervals. Seroconversion at 2 months after the third dose of vaccine was 96.30 percent in the children and 92.00 percent in the adults with mean anti-HBs titres of 800 mlU/ml and 353 mlU/ml respectively. The difference of anti-HBs levels between these two groups was statistically significant (p less than 0.05). Female adults had exhibited higher immune response to HB vaccine than male adults but there was no seroconversion difference between boys and girls. There were no serious local or systemic side effects of hepatitis B vaccination. It was concluded that active immunisation with plasma derived hepatitis B vaccine in non-immune children and adults is highly effective without any serious side effects or complications. The prevention of horizontal transmission of hepatitis B virus should be done by vaccination in children since they have a much better immune response to hepatitis B vaccine than adults.