Immunogenicity

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The HBsAg particle is the immunogen in both plasma-derived and recombinant hepatitis B vaccines. This envelope protein composed of several allelic subtype determinants but only one common group-specific determinant "a," which allows cross-protectivity among different subtypes [28,29]. Vaccinated subjects may have transiently detectable HBsAg in the serum within the first 24 hours. HBV vaccines stimulate active synthesis of anti-HBs conferring immunity. The first commercially available hepatitis B vaccine in the United States, licensed in 1981, was derived from chemically treated or heat-inactivated sub-viral particles that were obtained from plasma of chronic HBV carriers. Physician acceptance of these vaccines was initially impeded by the unfounded concern of the product carrying other blood-borne infectious agents [5]. Plasma-derived products still account for more than 80% of all hepatitis B vaccines used worldwide; however, in the United States the plasma-derived product has been completely replaced by recombinant vaccines.

Recombinant hepatitis B vaccine consists of nonglycosylated HBsAg particles that are produced by cloning the S gene via the yeast Saccharomyces cerevisiae. These newly synthesized HBsAg particles are then extracted from disrupted yeast cells, physicochemically purified, adsorbed on aluminum hydroxide, and preserved with thimerosal [10]. The first recombinant vaccine became available in the United States in 1986, and there are currently two approved products, Recombivax HB (Merck & Co., West Point,

Pennsylvania) and Engerix-B (Glaxo-SmithKline, Philadelphia, Pennsylvania) (Table 2). In addition, Recombivax HB is available as combination with hemophilus influenzae type b (Hib) vaccine (Comvax) for children. Furthermore, Engerix-B is available as combinations with hepatitis A vaccine (Twinrix) for adults, and with polio and diphtheria-tetanus-pertussis (DTP) vaccines (Pediatrix) for children. Concurrent administration of HBIG or other vaccines, such as Hib or DTP, does not interfere significantly with the antibody response to hepatitis B vaccine [10,30].

Only one among seven clinical series in the literature comparing the im-munogenicity of Recombivax HB and Engerix-B is a prospective randomized double-blind trial [31]. In this multicenter trial of 460 healthy subjects between 39 and 70 years of age, either Recombivax HB 10 mcg or Engerix-B 20 mcg was administered as three standard intramuscular doses over a period of 6 months [32]. The geometric mean titer (GMT) of anti-HBs 2 months after the last vaccine dose was significantly higher in the En-gerix-B group (840 mlU/mL versus 340 mlU/mL). The seroprotection rate, defined as anti-HBs titer > 10 mlU/mL, was higher in the Engerix-B group but did not reach statistical significance (91% versus 85%). In a separate prospective randomized but single-blind study, the superior immunogenicity of Engerix-B was only demonstrated in subjects who were aged 40 or older (87% versus 81%) [33].

The immunogenicity of other HBV antigens, including HBcAg, remains ill defined. Addition of the pre-S components neither enhances the immuno-gencity of HBV vaccines nor circumvents any immunologic unresponsiveness to the S protein [34]. In a single-blind multicenter trial where volunteers were assigned to receive hepatitis B vaccines containing S protein and pre-S2 of various doses, the titers of anti-HBs that were achieved correlated with the dosage of S protein, and not of pre-S2. Furthermore, the titers of anti-HBs achieved in each vaccine group were higher in those

Table 2

Recommended dosages of licensed hepatitis B vaccines in the United States

Table 2

Recommended dosages of licensed hepatitis B vaccines in the United States

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