• M D Young, W M Gooch, A J Zuckerman, W Du, B Dickson, and W C Maddrey.
• Medeva Group Development, Wayne, Pennsylvania 19087, USA.
• J. Med. Virol. 2001 Jul 1; 64 (3): 290-8.

AbstractHepatitis 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 two-dose regimen of the triple antigen vaccine than with the single antigen vaccine regimen. In adults at risk for a reduced response to hepatitis B vaccination [i.e., older adults (>/=40), the obese, males, and smokers], the triple antigen vaccine produced a significantly greater percentage of protected subjects (P < 0.001) and higher geometric mean titre (P < 0.001). Indeed as a three-dose/6 month regimen, the triple antigen vaccine raised the level of protection in these vulnerable subgroups to that seen when a single antigen vaccine is used in the optimal younger adult group. Both vaccines were well tolerated and had similar safety profiles. The most frequently (> or = 10%) reported adverse events with the use of either vaccine were pain at the site of injection (38% vs. 41% vs. 20% for the two-dose Hepacare regimen, the three-dose Hepacare regimen, and the three-dose Recombivax-HB regimen, respectively), infections at the site of injection (1% vs. 14% vs. 9%), headache (9% vs. 13% vs. 11%), and nausea (7% vs. 11% vs. 3%). It is concluded that in healthy normal adults, a triple antigen hepatitis B vaccine that contained S and pre-S antigens produced an enhanced immunological response. This was exemplified by the novel vaccine's ability to overcome factors such as advancing age (> or = 40 years), obesity, and smoking, each of which is known to reduce the potential for protection with present recombinant S only vaccines. A two-dose/1-month (0 and 1) regimen of this triple antigen vaccine was as effective as the standard three-dose/6 month (0, 1, and 6) regimen of present single antigen vaccines. (c) 2001 Wiley-Liss, Inc.

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