Timing of hepatitis B vaccination: Its effect on vaccine response in health care workers

doi:10.1016/j.vaccine.2007.08.025

Vaccine

Volume 25, Issue 43, 23 October 2007, Pages 7568-7572

https://doi.org/10.1016/j.vaccine.2007.08.025 Get rights and content

Abstract

We assessed the effect of timing and other biological variables on immune response among health care workers (HCW) vaccinated with hepatitis B vaccine. A total of 2.058 HCW received three doses and were tested for anti-HBs within 6 months. 92.2% of the HCW had evidence of seroprotection. Multivariable analysis showed that controlling for age, the estimated non-response OR associated with a delayed second dose was 2.16 (95% CI: 1.46, 3.18, p = 0.004). We found a decreasing response rate with increasing age. Particular attention should be given to those HCW who are late for the second vaccine dose and to older subjects.

Introduction

Health care workers (HCW) are at higher risk of acquiring the hepatitis B virus (HBV) infection [1]. Therefore, a three-dose series of hepatitis B vaccine administered at 0, 1, and 6 months has been recommended [2]. Between 5% and 10% of healthy subjects may not develop a protective titer of antibodies to hepatitis B surface antigen (anti-HBs) to vaccination [3], [4]. Vaccine response is reduced in persons who are older, male, who smoke, are overweight, immunocompromised [4], [5], [6], [7], [8], or have certain HLA haplotypes [9].

Under routine use, timing of vaccine dose frequently deviates from the recommended schedule. It is unclear how changes in timing between doses affect vaccine immunogenicity. The delay in the second dose has little effect on vaccine immune response [10], [11], [12]. However, in some studies it has resulted in a decreased response [13], [14]. The delay in the third dose leads to higher anti-HBs titres [10], [15]. Delays in receiving vaccination can be of great clinical significance, since those subjects experience longer periods of increased susceptibility. A better insight into the effect of delayed dose administration on vaccination response may help to identify persons at risk of non-response. The objectives of the study were (1) to determine the effect of the delay in dose administration on vaccine immune response, and (2) to determine the immunogenicity of hepatitis B vaccination under routine practice. In addition, we sought to assess the effect of other biological variables on the achievement of seroprotection.

Section snippets

Study design

Retrospective cohort study of HCW vaccinated against hepatitis B between 1986 and 2006. The study was conducted in two public teaching hospitals in Catalonia: Hospital Universitari de Bellvitge (Barcelona), and Hospital Universitari de Girona Dr. Josep Trueta (Girona). No subject identifier was obtained during data collection. Therefore, informed consent was not required.

Study population

Subjects were identified through a comprehensive review of hospital HCW records. We collected information of 2187 subjects

Results

A total of 2.187 HCW were identified as having an absence of HBV-markers previous to vaccination, having received the hepatitis B series, and a documented post-vaccination testing. Of these, 2.058 subjects were included in the study. The remaining 129 (5.9%) were excluded: 22 did not respect the minimum timing between the first two doses; 6 did not respect the minimum timing between the last two doses; and 101 did not determine anti-HBs titer within 1–6 months after the third dose. Among those

Discussion

This is a retrospective cohort study in 2 acute-hospitals in Catalonia. It has assessed the seroconversion rates among 2058 HCW who received either Hevac-B or Engerix B and were tested for anti-HBs within 6 months after their third dose. It has determined how changes in dosing schedule affect the rates of seroprotection achieved from the vaccination series and also the risk factors for a decreased immunogenicity.

One strength of this study is the large sample among recipients of a vaccine with a

References (30)

P. Bonanni et al.
Vaccination against hepatitis B in health care workers
Vaccine
(2001)
T. Coates et al.
Hepatitis B vaccines: assessment of the seroprotective efficacy of two recombinant DNA vaccines
Clin Ther
(2001)
F. Averhoff et al.
Immunogenicity of hepatitis B vaccine. Implications for persons at occupational risk of hepatitis B virus infection
Am J Prev Med
(1998)
S.C. Hadler et al.
Effect of timing of hepatitis B vaccine doses on response to vaccine in Yucpa Indians
Vaccine
(1989)
J. Wistrom et al.
Booster vaccination with recombinant hepatitis B vaccine 4 years after priming with one single dose
Vaccine
(1999)
J.M. Bayas et al.
Hepatitis B vaccination in prisons: the Catalonian experience
Vaccine
(1993)
T.L. Treadwell et al.
Immunogenicity of two recombinant hepatitis B vaccines in older individuals
Am J Med
(1993)
R.W. Joines et al.
A prospective, randomized, comparative US trial of a combination hepatitis A and B vaccine (Twinrix^®) with corresponding monovalent vaccines (Havrix^® and Engerix-B^®) in adults
Vaccine
(2001)
R. Mangione et al.
Delayed third hepatitis B vaccine dose and immune response
Lancet
(1995)
A. Floreani et al.
Long-term persistence of anti-HBs after vaccination against HBV: an 18-year experience in health care workers
Vaccine
(2004)

D.J. West et al.

Vaccine induced immunologic memory for hepatitis B surface antigen: implications for policy on booster vaccination

Vaccine

(1996)

A. Vilella et al.

The role of mobile phones in improving vaccination rates in travelers

Prev Med

(2004)

Centers for Disease Control. A comprehensive immunization strategy to eliminate transmission of hepatitis B virus...

K. Alimonos et al.

Prediction of response to hepatitis B vaccine in health care workers: whose titres of antibody to hepatitis B surface antigen should be determined after at three-dose series, and what are the implications in terms of cost-effectiveness?

Clin Infect Dis

(1998)

R.C. Wood et al.

Risk factors for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers

JAMA

(1993)

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Timing of hepatitis B vaccination: Its effect on vaccine response in health care workers

Abstract

Introduction

Section snippets

Study design

Study population

Results

Discussion

Vaccine

Clin Ther

Am J Prev Med

Vaccine

Vaccine

Vaccine

Am J Med

Vaccine

Lancet

Vaccine

Vaccine

Prev Med

Prediction of response to hepatitis B vaccine in health care workers: whose titres of antibody to hepatitis B surface antigen should be determined after at three-dose series, and what are the implications in terms of cost-effectiveness?

Clin Infect Dis

Risk factors for lack of detectable antibody following hepatitis B vaccination of Minnesota health care workers

JAMA