| HEPATITIS B VIRUS (HBV) VACCINATION
Need for boosters and significance of HBsAg escape mutants. HBV vaccine is recommended by the WHO for all newborn infants, as well as for adolescents, health care workers, and other groups at risk. Two issues regarding HBV vaccine remain uncertain: (1) how long will protection last, and (2) will mutant viruses that are not protected by the current vaccines arise. Two recent studies address these issues. Chung-Yi Lu and others at National Taiwan University measured anti-HBs titers in 2 cohorts of children 15 years after neonatal immunization with plasma-derived HBV vaccines. Group A comprised 78 children who were born to HBeAg+, HBsAg carrier mothers and developed protective levels of anti-HBs. Group B comprised 113 apparently healthy children whose anti-HBs titers after vaccination were unknown. The authors found that anti-HBs antibodies were undetectable in 29.9% of children in Group A and 62.4% of children in Group B. Anti-HBc was detected in 33.3% of children in Group A and 4.4% of children in Group B. One HBsAg carrier was detected in Group A and 4 in Group B. After a single booster dose of HBV vaccination, only 2.7% and 3.3% of children remained anti-HBs– in Groups A and B, respectively. This investigation demonstrated a waning immunity in a large proportion of children 15 years after neonatal immunization and suggested that booster vaccinations may be needed in seronegative subjects. However, it must be emphasized that initial immune response was not documented in Group B children, and it is possible that some children had inadequate rather than waning anti-HBs titer. More long-term and larger studies are needed to better delineate how long protection lasts. H-Y Hsu et al. conducted 3 nationwide serosurveys in Taiwan to determine the prevalence of HBV S mutants in the population. Mutations that occur in the “a” determinant of the gene that codes for HBsAg, the region where the immunogenic epitopes that are neutralized by anti-HBs are located, may render the virus undetectable by commercial assays and could allow the virus to escape neutralization by anti-HBs induced by conventional vaccines. Two types of mutations may occur: one that alters the antigenicity of one of the amino acids in HBsAg (most commonly involving a glycin- to-arginine change occurring at AA position 145), or a mutation that decreases expression of HBsAg. The first of these mutations results in a mutant HBV strain that may escape detection by monoclonal enzyme immunoassays but can often be detected by polyclonal assays. The second mutation can result in circulating levels of HBsAg below the threshold of detection of commercial assays. These HBV variants have been reported to occur infrequently in immunized groups and among infants who received HBV vaccine and hepatitis B immune globulin. The study by Hsu et al. tested persons who were HBsAg+ or had anti-HBc for the presence of HBV DNA. In those who were HBV DNA+, the prevalence of variants ranged from 8% at baseline to 20% to 28% at 5 to 15 years after the initiation of a universal infant HBV vaccine program. However, the prevalence of these variants in the entire population tested was <1% and did not increase with time. When these variants are found in individuals, the levels of HBV DNA are very low (2 to 3 logs), making it unlikely that HBV infection will be passed to others. Further studies are needed to determine if S variant infections can be transmitted and whether current vaccines provide cross-protection against mutants. (Lu C-Y Hepatology 2004;40:1415-1420; Hsu H-Y, et al. Gut 2004;53:1499-1503)
[此贴子已经被作者于2005-2-7 14:14:03编辑过] | 
发表于 2005-2-8 04:02
