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In this double-blind, randomized, controlled study, healthcare professionals with a history of inadequate response to currently available single-antigen hepatitis B vaccines confirmed by measuring hepatitis B surface antibody titer before entry to the study were revaccinated with a 20-g dose either of a novel triple-antigen (S, pre-S1, and pre-S2) recombinant vaccine or of a present single-antigen (S only) vaccine. Hepatitis B surface antibody titers were measured 8 weeks' post revaccination. A total of 925 individuals were randomized and vaccinated, of whom 915 (98.9%) completed the study and were included in the efficacy analysis. A single dose of the new triple-antigen hepatitis B vaccine (Hepacare) produced a successful response in over three quarters of these subjects who had not mounted an adequate response to current vaccines. The antibody response was statistically significantly superior (P ‫؍‬ .002) to that after a single dose of current vaccines. An evaluation of the overall response showed that only the triple-antigen vaccine was able to raise the average antibody response (geometric mean titer [GMT]) to over 100 IU/L. The superior effect of the new vaccine was most pronounced in subjects who were previously complete nonresponders to currently available hepatitis B vaccines. Both vaccines were well tolerated and had similar safety profiles. This study demonstrated that in healthcare workers who had responded inadequately to at least a full course of immunization (median, 5 doses), a single 20-g dose of a new triple-antigen vaccine induced protective antibody level in more vaccinees (P ‫؍‬ .002) and increased the average antibody titer (GMT) in those protected successfully to a greater degree (P < . 001) than a further attempt with a current vaccine (Engerix-B). (HEPATOLOGY 2001;34:798-802.)It is estimated that more than 2 billion people worldwide have been infected by the hepatitis B virus (HBV), and that currently there are about 350 million carriers. 1 Vaccination is the only approach to eradication of the disease, and the adoption of universal childhood vaccination against hepatitis B is now recommended 2 and implemented in some 100 countries. However, these programs have only been adopted in the last decade or so, and therefore there is a continuing need to protect those at high risk such as physicians and ancillary healthcare workers. 3 In this context, it is important to recognize that present vaccination programs are not completely successful, and that 10% to 15% of the normal adult population fail to produce hepatitis B surface antibody (anti-HBs) titers above the critical values for protection (10 IU/L). 4,5 The HBV consists of an inner core and an outer surface coat (hepatitis B surface antigen [HBsAg]). The inner core contains double-stranded DNA, DNA polymerase, hepatitis B core antigen, and the e antigen. Several antigenic determinants (a, d, y, w, and r) are found on HBsAg particles. The HBV genome consists of several open reading frames in addition to that for the common surface antigen...

Present hepatitis B vaccines use multidose prolonged regimens, which even healthcare workers at risk do not always complete. Moreover, when vaccination is completed there remain some who fail to achieve adequate protection. The protection of adults at risk could be improved if there were a more potent vaccine and/or a shorter vaccination regimen available. Vaccine-naive adults were randomized to vaccination with either Engerix-B (SmithKline Biologicals, Rixensart, Belgium) or a novel triple antigen (S, pre-S1, and pre-S2) recombinant vaccine (Hepacare; Medeva Pharma Plc, Speke, UK). The primary efficacy parameter was the degree of seroprotection 6 or 7 months (26 ؎ 2 weeks) after beginning vaccination. A total of 304 adults entered the study. Of these, 16 failed to complete the study (9 on Hepacare and 7 on Engerix-B). With the Engerix-B standard (0, 1, 6) regimen, 88% of subjects were protected by month 7, whereas with the triple antigen vaccine a 2-dose regimen (0, 1) provided equivalent protection (91%) within 6 months and a 3-dose (0, 1, 6) regimen was significantly superior (98% seroprotected by 7 months after starting vaccination P < .001). With adults at risk for a suboptimal response (i.e., older adults, the obese, men, and smokers) the triple antigen vaccine produced a greater degree of protection. The vaccines had similar safety profiles. Both vaccines were well tolerated. In healthy normal adults, a triple antigen hepatitis B vaccine containing S and pre-S antigens produced an enhanced immunologic response and was as effective as a 2-and 3-dose regimen. (HEPATOLOGY 2001;34:372-376.)Although hepatitis B is largely a disease of the developing world, it is still a problem in the developed world. The estimated annual incidence of new infections of hepatitis B in the United States has varied from 200,000 to 300,000 new cases each year over the past decade. 1-3 Much of the disease is subclinical and a recent estimate 4 has suggested some 6-fold under-reporting with a true incidence of 1,000,000 new cases every year in Europe alone. All this is despite the availability of vaccines for over 2 decades.Although much of the problem has been the limited population in whom the vaccine was used initially there are other issues. First, all hepatitis B vaccines to date show a decreased response in certain subjects such as older adults, men, smokers, and the obese as well as when given intradermally or in the buttocks rather than in the deltoid muscle. [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] Second, present vaccines are usually given in a 6-month/3-dose (0, 1, and 6 months) regimen. 20,21 This implies that protection is not provided to a significant number of adults until some 7 months after beginning a course of vaccination. The implication is reinforced by the development of a so-called "accelerated course" of 3 doses given within 2 months (0, 1, and 2 months) for those who require rapid protection. 20,22 Unfortunately, this course does not deliver longer-term protection, and a booster dose at 12 mon...

Hepatitis B and its sequelae are a major public health problem. Vaccines have been available for almost 20 years; however the disease still remains a global problem. Many factors contribute to the failure to control hepatitis B, including the limited nature of the vaccination programs implemented initially. Only relatively recently has mass childhood vaccination begun to be implemented and vaccination of high-risk groups, other than healthcare workers, is still not general policy. Additional factors contributing to continued persistence of hepatitis B in the developed world are that the present vaccines are not fully used by those recommended to be vaccinated and even when vaccination is carried out appropriately, there remain some who fail to achieve adequate protection. Clearly, the protection of at-risk groups who have inadequate response to current vaccines, and those who are unwilling or unable to comply with protracted multi-dose vaccine regimens, could be improved if there were a more potent vaccine and/or a shorter vaccination regimen available. Adults who had never been vaccinated against hepatitis B were randomised to receive a vaccination course of either a present single antigen (S) vaccine (Recombivax-HB) or a novel triple antigen (S, pre-S1, and pre-S2) recombinant vaccine (Hepacare Medeva Pharma plc). Doses were given at baseline and 1 month and 6 months later. Hepatitis B surface antibody (anti-HBs) levels were measured at 2, 4, 6, and 7 months after beginning vaccination. The primary efficacy parameter was the degree of protection, measured as the percentage of subjects with anti-HBs titres > or = 10 IU/L, 6 or 7 months (26 +/- 2 weeks) after beginning vaccination. A total of 303 adult subjects entered the study and were vaccinated. Of these, 11 failed to complete the study (4 on Hepacare and 7 on Recombivax-HB); however all but 2 (1 to receive the triple antigen vaccine and 1 to receive Recombivax-HB) were included in the intent-to-treat population for efficacy evaluation. Treatment randomisation was stratified at entry based on age (above and below 40 years old) and gender. The standard three-dose/6-month vaccination regimen of the single antigen vaccine protected 83% of subjects by 7 months after starting vaccination whereas the triple antigen vaccine as a two-dose/1-month regimen protected 88% within 6 months and as a three-dose/6-month regimen protected 97% by 7 months after starting vaccination. Thus the protection rate provided by the shortened (0, 1) regimen of the novel vaccine was "essentially equivalent" (i.e., not statistically inferior) to that provided by the full (0, 1, and 6) regimen of today's vaccine (88% vs. 81%, P < 0.001), and the protection rate provided by a three-dose/6-month (0, 1, and 6) regimen of the new vaccine was significantly superior to that provided by present vaccines (97% vs. 83% P < 0.001). The percentage of subjects protected increases with time after beginning vaccination and at all time points up to and including 6 months was significantly greater with the ...