Comparison of a triple antigen and a single antigen recombinant vaccine for adult hepatitis B vaccination

Hepatitis B and its sequelae are a major public health problem. Vaccines ha ve 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 in itially. Only relatively recently has mass childhood vaccination begun to b e implemented and vaccination of high-risk groups, other than healthcare wo rkers, is still not general policy. Additional factors contributing to cont inued persistence of hepatitis B in the developed world are that the presen t vaccines are not fully used by those recommended to be vaccinated and eve n 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 unwilli ng or unable to comply with protracted multi-dose vaccine regimens, could b e 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 singl e antigen (S) vaccine (Recombivax-HB) or a novel triple antigen (S, pre-Si, and pre-S2) recombinant vaccine (Hepacare(K) Medeva Pharma pie). Doses wer e given at baseline and 1 month and 6 months later. Hepatitis B surface ant ibody (anti-HBs) levels were measured at 2, 4, 6, and 7 months after beginn ing vaccination. The primary efficacy parameter was the degree of protectio n, measured as the percentage of subjects with a nti-H Bs titres greater th an or equal to 10 IU/L, 6 or 7 months (26 +/-2 weeks) after beginning vacci nation. 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 Recombi vax-HB); however all but 2 (1 to receive the triple antigen vaccine and 1 t o receive Recombivax-HB) were included in the intent-to-treat population fo r efficacy evaluation. Treatment randomisation was stratified at entry base d 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 vacc ination. 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 vac cine (88% vs. 81%, P <0.001), and the protection rate provided by a three-d ose/6-month (0, 1, and 6) regimen of the new vaccine was significantly supe rior to that provided by present vaccines (97% vs. 83% P <0.001). The perce ntage of subjects protected increases with time after beginning vaccination and at all time points up to and including 6 months was significantly grea ter with the two-dose regimen of the triple antigen vaccine than with the s ingle antigen vaccine regimen. In adults at risk for a reduced response to hepatitis B vaccination [i.e., older adults (greater than or equal to 40), the obese, males, and smokers], the triple antigen vaccine produced a signi ficantly greater percentage of protected subjects (P <0.001) and higher geo metric mean titre (P <0.001). Indeed as a three-dose/6 month regimen, the t riple antigen vaccine raised the level of protection in these vulnerable su bgroups to that seen when a single antigen vaccine is used in the optimal y ounger adult group. Both vaccines were well tolerated and had similar safety profiles. The most frequently (greater than or equal to 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 sit e of injection (1% vs. 14% vs. 9%), headache (9% vs. 13% vs. 11%), and naus ea (7% vs. 11% vs. 3%). It is concluded that in healthy normal adults, a tr iple antigen hepatitis B vaccine that contained S and pre-S antigens produc ed an enhanced immunological response. This was exemplified by the novel va ccine's ability to overcome factors such as advancing age (greater than or equal to 40 years), obesity, and smoking, each of which is known to reduce the potential for protection with present recombinant S only vaccines. A tw o-dose/1-month (0 and 1) regimen of this triple antigen vaccine was as effe ctive as the standard three-dose/6 month (0, 1, and 6) regimen of present s ingle antigen vaccines. J, Med. Virol. 64:290-298, 2001. (C) 2001 Wiley-Lis s, Inc.