Vaccine 21 (2002) 243–246 Antihepatitis B response to hepatitis B vaccine administered simultaneously with tetanus toxoid in nonresponder individuals Emine Sönmez a,* , Ali Suha Sönmez b , Ya¸ sar Bayindir c , Diler Coskun a , Sedat Aritürk a a Department of Infectious Diseases and Clinical Microbiology, Medical Faculty of Kadir Has University, Vefabey Sokak No. 5, 80 810 Gayrettepe, Istanbul, Turkey b Süleymaniye Maternity and Women’s Disease Research and Teaching Hospital, Istanbul, Turkey c Department of Infectious Diseases and Clinical Microbiology, Medical Faculty of ˙ Inönü University, Malatya, Turkey Received 1 January 2002; received in revised form 1 August 2002; accepted 1 September 2002 Abstract In this prospective study, our aim was to test the effect of simultaneous administration of preS2 and S containing recombinant hepatitis B vaccine (S2SRHB) with tetanus toxoid (TT) to the individuals who did not respond after three doses of hepatitis B vaccine previously. There were three groups (healthy individuals, pregnant women, hemodialysis patients), each was divided into two subgroups as groups A and B. Group A received S2SRHB + TT and group B received only S2SRHB. We found that in groups receiving both vaccines, both seroconversion rate and antibody titer level were significantly higher (P< 0.05). In conclusion, simultaneous administration of S2SRHB + TT is more effective than administration of S2SRHB alone. © 2002 Elsevier Science Ltd. All rights reserved. Keywords: Hepatitis B vaccine; Tetanus toxoid; Nonresponder 1. Introduction Some healthy individuals, hemodialysis patients or hepati- tis B carrier mothers’ neonates may not respond to S2SRHB vaccine [1–4]. The mechanism causing nonresponsiveness to hepatitis B vaccines in humans still remains unexplained. However, peripheric blood mononuclear cells (PBMC) from nonresponders did not proliferate to HBsAg in vitro, but they vigorously proliferated upon stimulation with tetanus toxoid (TT) [5]. It was found that in vitro response of PBMC to stimulation with HBsAg was correlated with serum anti-HBs titer and the deletion of CD8 + T-cells. Nonresponders have a lower cytokine response to the vaccine than responders [6]. Patients with uremia up to 30% fail to respond to the usual vaccination schedules. Coinfection with hepatitis C of uremia patients may lower the response rate [7]. Genetic de- terminants are also present in uremic patients [8]. Repeated IM booster injections is recommended for such patients. If this does not achieve the goal, revaccination with regular IM or ID injection at short intervals is thought to be appropriate until satisfactory response has been achieved [3,9,10]. * Corresponding author. Tel.: +90-212-275-2636x136; fax: +90-212-275-6108. E-mail address: suhas@anet.net.tr (E. Sönmez). In this study, we compared the antibody responses to S2SRHB + TT and S2SRHB alone in different nonrespon- der groups to S2SRHB vaccine previously. 2. Materials and methods Seventy-six subjects (age range 18–60 years, mean age 30.67 ± 6.97 years) were included in the study. All of them were negative for all HBV markers (by ELISA, ORGANON) and all received at least three shots of S2SRHB vaccine (recombinant DNA vaccine, Genhevac, Pasteur) but still remained negative for anti-HBs antibody (anti-HBs <10 IU/l) which are named as nonresponders. All subjects were scanned for the liver function tests (ALT and AST) and rheumatoid factor. The individuals with normal ALT and AST levels and negative rheumatoid factor were included in the study. There were three different groups of subjects (group I, otherwise healthy individuals, n = 40, mean age 29.01 ±5.2 years; group II, pregnant women, n = 12, mean age 28.05 ± 7.0 years; group III, hemodialysis patients, n = 24, mean age ±8.72 years). They were divided into two subgroups as A and B. Group IA (n = 25, 13 males and 12 females), group IIA (n = 7, 7 females) and group IIIA (n = 13, 9 males and 4 females) received S2SRHB vaccine (recombinant DNA 0264-410X/02/$ – see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII:S0264-410X(02)00452-8