There was a suggestion that women responded better than men to vaccination. The second-generation or yeast-derived vaccine (YDV) was found to have similar efficacy in healthy recipients to the earlier LDK378 PDV. An early investigation found 97% seroconversion in 32

HD patients with the YDV.56 Bruguera et al. examined the YDV in over 270 HD patients.57 Using a four-dose schedule and dosing at 0, 1, 2 and 6 months with 40 µg vaccine, 69% of patients achieved an anti-HBs titre of ≥10 IU/L (considered protective). If the fourth dose was given at 12 months, the seroprotection rate reached 76%. When the vaccine is used in immunocompetent individuals using a three-dose schedule, a 90–95% seroprotection rate is expected. Clearly, in vaccine recipients with renal failure, the rates are substantially lower. In an attempt to improve seroconversion rates, current buy GW-572016 recommendations state that dialysis patients should receive higher vaccine doses than individuals with normal renal function. As such,

40 µg of Recombivax HB at 0, 1 and 6 months, or 40 µg of Engerix B at 0, 1, 2 and 6 months should be administered. The best reported response rates to these schedules are <85% achieving seroprotection.58,59 Not only is the response to the vaccine blunted, but anti-HBs levels decline more rapidly after immunization in HD patients compared with healthy individuals, such that in 41% of responsive patients the levels are undetectable at three years.60 Other reports suggest that in up to 42% there are no detectable anti-HBs levels one year after vaccination.26 The likelihood of a seroconversion response to hepatitis B vaccine decreases as renal failure progresses. As mentioned above, Köhler et al. found a far superior response to the PDV in their small group of pre-dialysis patients.53 This has been borne out by other studies more recently using YDV.61,62 As a result, guidelines also recommended that patients with CKD be vaccinated as early as possible in the course of their renal disease. Although vaccinating patients before dialysis makes immunological sense, there are substantial cost implications

in vaccinating Alanine-glyoxylate transaminase much larger numbers of patients: Many pre-dialysis patients will never progress to renal replacement therapy, succumbing instead to their comorbidities. Vaccine adjuvants have been studied in HD patients. The addition of granulocyte-macrophage colony-stimulating factor and interleukin-2 has not been consistently successful in improving response rates.63,64 Likewise, studies have failed to show a significant, durable benefit of interferons or thymopentin.65–67 Alternatively, a more recent vaccine formulation (HBV-AS04) consisting of standard Engerix B YDV with adjuvant 3-O-desacyl-40-monophosphoryl lipid A, has shown the ability to provide earlier and greater anti-HBs responses than the standard vaccine.