Antibody production in response to hepatitis B surface antigen in a combination hepatitis A/hepatitis B vaccine.

To the Editor—It was with interest that we read the study by Frey et al. [1], which describes a randomized trial in which 3 manufacturing consistency lots of a combined hepatitis A and B vaccine were compared with the corresponding monovalent vaccines. The authors observed a nonsatisfactory response to the hepatitis B component in the combined vaccine. We are concerned that this report may be misleading, because SmithKline Beecham is mentioned on 2 occasions in the report in either misleading or inaccurate statements. The first instance is in the last paragraph of the introduction [1, page 2019]. As it is written, the reader may incorrectly infer that the vaccine used in this trial was Twinrix (hepatitis A inactivated and hepatitis B [recombinant], SmithKline Beecham Biologicals, Rixensart, Belgium). In fact, the product under discussion in the article was an unnamed combination hepatitis A and B vaccine, developed by Merck & Co. and tested in a 2-dose schedule. In the Materials and Methods section, it is incorrectly stated that RECOMBIVAX HB/H-B-VAXII is manufactured by SmithKline Beecham [1, page 2019], whereas, in fact, it is manufactured and distributed by Merck & Co.; SmithKline Beecham Biologicals manufactures Engerix-B (hepatitis B vaccine [recombinant]). The above statements might lead to the misconception that interference with the hepatitis B response may occur after administration of any combined hepatitis A and B vaccine. However, there are sufficient published data to demonstrate that SmithKline Beecham Biologicals’ combined hepatitis A and B vaccine, Twinrix, administered on a 0-, 1-, 6-month schedule, induces a strong immune response to both vaccine components. Pooled data from 6 pivotal clinical trials [2] carried out in young adults demonstrated high seroprotection rates and geometric mean titers (GMTs) against hepatitis B after vaccination with Twinrix (on a 0-, 1-, and 6-month schedule), as is shown in table 1. Additionally, in a US study conducted in adults (more than half were 140 years old), the immunogenicity of Twinrix (administered as a 3-dose series) was compared with separate injections of the corresponding monovalent products. A better immune response to the hepatitis B component was demonstrated in the combined vaccine than in the monovalent vaccine [3]. After the third dose, 95.1% of subjects receiving Twinrix and 92.2% of subjects receiving Engerix-B had protective titers. GMTs were 2099 mIU/mL and 1871 mIU/mL for Twinrix and Engerix-B, respectively. In conclusion, although Frey et al. [1] did show interference with the hepatitis B response after administration of the combination hepatitis A and B vaccine developed by Merck & Co., SmithKline Beecham Biologicals’ combination hepatitis A and B vaccine, Twinrix, shows no evidence of interference with either component.