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Do patients who received only two doses of hepatitis B vaccine need a booster?
Author(s)
Alexandra Junewicz, BA
Andrei Brateanu, MD, FACP
Craig Nielsen, MD, FACP

The Advisory Committee on Immunization Practices (ACIP) currently recommends that people who have not completed the three-dose vaccination series against hepatitis B virus (HBV) should receive the missed doses: ie, the three-dose regimen does not need to be restarted.1 However, evidence suggests that a two-dose regimen may provide adequate seroprotection for healthy young adults.

As the three-dose regimen has been shown to protect 90% to 100% of adults,2 it has gained widespread acceptance and is now standard clinical practice.2 However, deviating from the three-dose regimen may not leave healthy young adults vulnerable to HBV infection.

RECOMMENDED DOSES AND SCHEDULES

Widespread use of the three-dose regimen for HBV stemmed from the first clinical evaluation of the recombinant vaccine, in which three 10-μg doses were given at 0, 1, and 6 months to healthy, low-risk adult volunteers.3 This regimen was shown to provide seroprotection in over 95% of adolescents and 90% of healthy adults.2

Currently, three HBV vaccines for adults are approved in the United States: Recombivax HB, Engerix-B, and Twinrix (Table 1). While Recombivax has a seroprotection rate of 89% in healthy adults over age 40, it has higher seroprotection rates in younger people: eg, two doses of Recombivax given 4 to 6 months apart provide seroprotection to 99% of children aged 11 to 15.4 On the other hand, patients on hemodialysis require three 40-μg doses of Recombivax or four 40-μg doses of Engerix-B.

Evidence for a two-dose regimen

Since the development of the recombinant HBV vaccine used today, studies have shown that a two-dose regimen offers seroprotection comparable with, if not better than, the three-dose regimen in adolescents and healthy young adults. Marsano et al5 found that with a two-dose regimen, 96% to 99% of young adults attained seroprotection, with immune memory persisting for up to 2 years.5 Moreover, Cassidy et al6 randomized adolescents to a two-dose or a three-dose regimen and found the two regimens to be equally effective in conferring immunogenicity and immunologic memory.6

Other studies in adolescents have confirmed these findings and offered new evidence in support of the two-dose regimen.7,8 For example, studies found that the two-dose regimen conferred seroprotection at even lower doses than previously studied, and that it conferred immune memory lasting at least 5 years.6,7

However, because these studies were conducted in adolescents and healthy young adults, the findings may not hold true for other populations. Studies suggest that the three-dose regimen is best for those over age 40. Moreover, it is advisable to adhere to a three-dose regimen when treating people at high risk of contracting HBV, such as health care workers; people with chronic liver disease, diabetes mellitus, or end-stage renal disease on hemodialysis; people who have multiple sex partners; and men who have sex with men.

The impact of long intervals between doses

Although the aforementioned studies focused on a two-dose regimen with a 6-month interval, longer intervals between doses do not impair seroprotection and in some cases may even prove beneficial. Heron et al9 demonstrated that a two-dose regimen with a 12-month interval induces seroprotection as effectively as a standard three-dose or two-dose regimen with a 6-month interval.9 Moreover, studies of the impact of deviating from a three-dose regimen found that intervals of longer than 1 year did not impede seroprotection. Not only may seroprotection be attained with intervals of 5 to 10 years before the final dose, but final antibody levels tend to increase with increasing time between doses.10

Nevertheless, even though an extended interval between doses may prove beneficial after the final dose is received, delaying doses may leave patients unprotected. Indeed, alternative three-dose and even four-dose schedules with shorter intervals between doses exist for certain high-risk populations, such as those recently exposed to HBV and travelers to areas of high prevalence. Therefore, intentionally extending intervals between doses may be inappropriate.

SEROPROTECTION AND PROTECTION AGAINST INFECTION

Legitimate concerns exist about the final antibody level attained with a two-dose regimen, which is typically lower than that attained with a three-dose regimen. As HBV antibody levels decline with time, lower final antibody levels theoretically increase the risk of losing seroprotection. Study of vaccine efficacy has defined seroprotection as antibody levels greater than or equal to 10 mIU/mL.11 Yet evidence suggests that even when antibody levels drop below this level, the risk of symptomatic HBV infection does not increase. Evidence also suggests that immune memory outlasts the presence of seroprotective antibody levels, indicating that true protection against significant infection does not necessarily correlate with, and may even exceed, seroprotection.2 This may relate to HBV’s long incubation period, which allows memory cells time to generate an effective immune response.10 For example, Floreani et al12 showed that even though 15% of adults lost seroprotective antibody levels 10 years after vaccination, none demonstrated hepatitis B antigen reactivity or seroconversion.

POSTVACCINATION TESTING AND ADDITIONAL DOSES

At times, it may be wise to measure antibody levels after the final dose to confirm seroprotection. Seroprotection should be documented when knowledge of the patient’s immune status will affect subsequent management. As recommended by the US Centers for Disease Control and Prevention, health care workers, hemodialysis patients, immunocompromised patients, and sexual partners of patients with chronic HBV infection should undergo antibody testing 1 to 2 months after the completion of a three-dose vaccination regimen. Hemodialysis patients require annual confirmation of seroprotection and should receive booster doses of HBV vaccine if necessary.

Postvaccination testing (quantitative HBV surface antibody testing) costs about the same as a single dose of HBV vaccine. Therefore, if postvaccination testing is considered because of missed vaccine doses, it may be more cost-efficient to simply administer the missed dose.

References
  1. Department of Health and Human Services. Appendix A Immunization Management Issues. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5516a2.htm. Accessed April 6, 2014.
  2. Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis 2011; 53:68–75.
  3. Scolnick EM, McLean AA, West DJ, McAleer WJ, Miller WJ, Buynak EB. Clinical evaluation in healthy adults of a hepatitis B vaccine made by recombinant DNA. JAMA 1984; 251:2812–2815.
  4. Merck and Co, Inc. 1998. Recombivax HB. http://www.merck.com/product/usa/pi_circulars/r/recombivax_hb/re-combivax_pi.pdf. Accessed April 7, 2014.
  5. Marsano LS, West DJ, Chan I, et al. A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults. Vaccine 1998; 16:624–629.
  6. Cassidy WM, Watson B, Ioli VA, Williams K, Bird S, West DJ. A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatrics 2001; 107:626–631.
  7. Van Damme P, Moiseeva A, Marichev I, et al. Five years follow-up following two or three doses of a hepatitis B vaccine in adolescents aged 11–15 years: a randomised controlled study. BMC Infect Dis 2010; 10:357.
  8. Heron L, Selnikova O, Moiseieva A, et al. Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11–15 years: a randomised controlled trial. Vaccine 2007; 25:2817–2822.
  9. Heron LG, Chant KG, Jalaludin BB. A novel hepatitis B vaccination regimen for adolescents: two doses 12 months apart. Vaccine 2002; 20:3472–3476.
  10. Jackson Y, Chappuis F, Mezger N, Kanappa K, Loutan L. High immunogenicity of delayed third dose of hepatitis B vaccine in travellers. Vaccine 2007; 25:3482–3484.
  11. Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis 1999; 179:489–492.
  12. Floreani A, Baldo V, Cristofoletti M, et al. Long-term persistence of anti-HBs after vaccination against HBV: an 18 year experience in health care workers. Vaccine 2004; 22:607–610.
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Author and Disclosure Information

Alexandra Junewicz, BA
Case Western Reserve University, Cleveland, OH

Andrei Brateanu, MD, FACP
Department of Internal Medicine, Cleveland Clinic

Craig Nielsen, MD, FACP
Department of Internal Medicine, Cleveland Clinic

Address: Andrei Brateanu, MD, Department of Internal Medicine, NA10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: abratean@ccf.org

Issue
Cleveland Clinic Journal of Medicine - 81(6)
Publications
Cleveland Clinic Journal of Medicine
Topics
Adolescent Medicine
Infectious Diseases
Men's Health
Women's Health
Vaccines
Page Number
346-348
Sections
1-Minute Consult
Author(s)
Alexandra Junewicz, BA
Andrei Brateanu, MD, FACP
Craig Nielsen, MD, FACP
Author(s)
Alexandra Junewicz, BA
Andrei Brateanu, MD, FACP
Craig Nielsen, MD, FACP
Author and Disclosure Information

Alexandra Junewicz, BA
Case Western Reserve University, Cleveland, OH

Andrei Brateanu, MD, FACP
Department of Internal Medicine, Cleveland Clinic

Craig Nielsen, MD, FACP
Department of Internal Medicine, Cleveland Clinic

Address: Andrei Brateanu, MD, Department of Internal Medicine, NA10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: abratean@ccf.org

Author and Disclosure Information

Alexandra Junewicz, BA
Case Western Reserve University, Cleveland, OH

Andrei Brateanu, MD, FACP
Department of Internal Medicine, Cleveland Clinic

Craig Nielsen, MD, FACP
Department of Internal Medicine, Cleveland Clinic

Address: Andrei Brateanu, MD, Department of Internal Medicine, NA10, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; e-mail: abratean@ccf.org

Article PDF
media_ee39a8d_346.pdf
Article PDF
media_ee39a8d_346.pdf

The Advisory Committee on Immunization Practices (ACIP) currently recommends that people who have not completed the three-dose vaccination series against hepatitis B virus (HBV) should receive the missed doses: ie, the three-dose regimen does not need to be restarted.1 However, evidence suggests that a two-dose regimen may provide adequate seroprotection for healthy young adults.

As the three-dose regimen has been shown to protect 90% to 100% of adults,2 it has gained widespread acceptance and is now standard clinical practice.2 However, deviating from the three-dose regimen may not leave healthy young adults vulnerable to HBV infection.

RECOMMENDED DOSES AND SCHEDULES

Widespread use of the three-dose regimen for HBV stemmed from the first clinical evaluation of the recombinant vaccine, in which three 10-μg doses were given at 0, 1, and 6 months to healthy, low-risk adult volunteers.3 This regimen was shown to provide seroprotection in over 95% of adolescents and 90% of healthy adults.2

Currently, three HBV vaccines for adults are approved in the United States: Recombivax HB, Engerix-B, and Twinrix (Table 1). While Recombivax has a seroprotection rate of 89% in healthy adults over age 40, it has higher seroprotection rates in younger people: eg, two doses of Recombivax given 4 to 6 months apart provide seroprotection to 99% of children aged 11 to 15.4 On the other hand, patients on hemodialysis require three 40-μg doses of Recombivax or four 40-μg doses of Engerix-B.

Evidence for a two-dose regimen

Since the development of the recombinant HBV vaccine used today, studies have shown that a two-dose regimen offers seroprotection comparable with, if not better than, the three-dose regimen in adolescents and healthy young adults. Marsano et al5 found that with a two-dose regimen, 96% to 99% of young adults attained seroprotection, with immune memory persisting for up to 2 years.5 Moreover, Cassidy et al6 randomized adolescents to a two-dose or a three-dose regimen and found the two regimens to be equally effective in conferring immunogenicity and immunologic memory.6

Other studies in adolescents have confirmed these findings and offered new evidence in support of the two-dose regimen.7,8 For example, studies found that the two-dose regimen conferred seroprotection at even lower doses than previously studied, and that it conferred immune memory lasting at least 5 years.6,7

However, because these studies were conducted in adolescents and healthy young adults, the findings may not hold true for other populations. Studies suggest that the three-dose regimen is best for those over age 40. Moreover, it is advisable to adhere to a three-dose regimen when treating people at high risk of contracting HBV, such as health care workers; people with chronic liver disease, diabetes mellitus, or end-stage renal disease on hemodialysis; people who have multiple sex partners; and men who have sex with men.

The impact of long intervals between doses

Although the aforementioned studies focused on a two-dose regimen with a 6-month interval, longer intervals between doses do not impair seroprotection and in some cases may even prove beneficial. Heron et al9 demonstrated that a two-dose regimen with a 12-month interval induces seroprotection as effectively as a standard three-dose or two-dose regimen with a 6-month interval.9 Moreover, studies of the impact of deviating from a three-dose regimen found that intervals of longer than 1 year did not impede seroprotection. Not only may seroprotection be attained with intervals of 5 to 10 years before the final dose, but final antibody levels tend to increase with increasing time between doses.10

Nevertheless, even though an extended interval between doses may prove beneficial after the final dose is received, delaying doses may leave patients unprotected. Indeed, alternative three-dose and even four-dose schedules with shorter intervals between doses exist for certain high-risk populations, such as those recently exposed to HBV and travelers to areas of high prevalence. Therefore, intentionally extending intervals between doses may be inappropriate.

SEROPROTECTION AND PROTECTION AGAINST INFECTION

Legitimate concerns exist about the final antibody level attained with a two-dose regimen, which is typically lower than that attained with a three-dose regimen. As HBV antibody levels decline with time, lower final antibody levels theoretically increase the risk of losing seroprotection. Study of vaccine efficacy has defined seroprotection as antibody levels greater than or equal to 10 mIU/mL.11 Yet evidence suggests that even when antibody levels drop below this level, the risk of symptomatic HBV infection does not increase. Evidence also suggests that immune memory outlasts the presence of seroprotective antibody levels, indicating that true protection against significant infection does not necessarily correlate with, and may even exceed, seroprotection.2 This may relate to HBV’s long incubation period, which allows memory cells time to generate an effective immune response.10 For example, Floreani et al12 showed that even though 15% of adults lost seroprotective antibody levels 10 years after vaccination, none demonstrated hepatitis B antigen reactivity or seroconversion.

POSTVACCINATION TESTING AND ADDITIONAL DOSES

At times, it may be wise to measure antibody levels after the final dose to confirm seroprotection. Seroprotection should be documented when knowledge of the patient’s immune status will affect subsequent management. As recommended by the US Centers for Disease Control and Prevention, health care workers, hemodialysis patients, immunocompromised patients, and sexual partners of patients with chronic HBV infection should undergo antibody testing 1 to 2 months after the completion of a three-dose vaccination regimen. Hemodialysis patients require annual confirmation of seroprotection and should receive booster doses of HBV vaccine if necessary.

Postvaccination testing (quantitative HBV surface antibody testing) costs about the same as a single dose of HBV vaccine. Therefore, if postvaccination testing is considered because of missed vaccine doses, it may be more cost-efficient to simply administer the missed dose.

The Advisory Committee on Immunization Practices (ACIP) currently recommends that people who have not completed the three-dose vaccination series against hepatitis B virus (HBV) should receive the missed doses: ie, the three-dose regimen does not need to be restarted.1 However, evidence suggests that a two-dose regimen may provide adequate seroprotection for healthy young adults.

As the three-dose regimen has been shown to protect 90% to 100% of adults,2 it has gained widespread acceptance and is now standard clinical practice.2 However, deviating from the three-dose regimen may not leave healthy young adults vulnerable to HBV infection.

RECOMMENDED DOSES AND SCHEDULES

Widespread use of the three-dose regimen for HBV stemmed from the first clinical evaluation of the recombinant vaccine, in which three 10-μg doses were given at 0, 1, and 6 months to healthy, low-risk adult volunteers.3 This regimen was shown to provide seroprotection in over 95% of adolescents and 90% of healthy adults.2

Currently, three HBV vaccines for adults are approved in the United States: Recombivax HB, Engerix-B, and Twinrix (Table 1). While Recombivax has a seroprotection rate of 89% in healthy adults over age 40, it has higher seroprotection rates in younger people: eg, two doses of Recombivax given 4 to 6 months apart provide seroprotection to 99% of children aged 11 to 15.4 On the other hand, patients on hemodialysis require three 40-μg doses of Recombivax or four 40-μg doses of Engerix-B.

Evidence for a two-dose regimen

Since the development of the recombinant HBV vaccine used today, studies have shown that a two-dose regimen offers seroprotection comparable with, if not better than, the three-dose regimen in adolescents and healthy young adults. Marsano et al5 found that with a two-dose regimen, 96% to 99% of young adults attained seroprotection, with immune memory persisting for up to 2 years.5 Moreover, Cassidy et al6 randomized adolescents to a two-dose or a three-dose regimen and found the two regimens to be equally effective in conferring immunogenicity and immunologic memory.6

Other studies in adolescents have confirmed these findings and offered new evidence in support of the two-dose regimen.7,8 For example, studies found that the two-dose regimen conferred seroprotection at even lower doses than previously studied, and that it conferred immune memory lasting at least 5 years.6,7

However, because these studies were conducted in adolescents and healthy young adults, the findings may not hold true for other populations. Studies suggest that the three-dose regimen is best for those over age 40. Moreover, it is advisable to adhere to a three-dose regimen when treating people at high risk of contracting HBV, such as health care workers; people with chronic liver disease, diabetes mellitus, or end-stage renal disease on hemodialysis; people who have multiple sex partners; and men who have sex with men.

The impact of long intervals between doses

Although the aforementioned studies focused on a two-dose regimen with a 6-month interval, longer intervals between doses do not impair seroprotection and in some cases may even prove beneficial. Heron et al9 demonstrated that a two-dose regimen with a 12-month interval induces seroprotection as effectively as a standard three-dose or two-dose regimen with a 6-month interval.9 Moreover, studies of the impact of deviating from a three-dose regimen found that intervals of longer than 1 year did not impede seroprotection. Not only may seroprotection be attained with intervals of 5 to 10 years before the final dose, but final antibody levels tend to increase with increasing time between doses.10

Nevertheless, even though an extended interval between doses may prove beneficial after the final dose is received, delaying doses may leave patients unprotected. Indeed, alternative three-dose and even four-dose schedules with shorter intervals between doses exist for certain high-risk populations, such as those recently exposed to HBV and travelers to areas of high prevalence. Therefore, intentionally extending intervals between doses may be inappropriate.

SEROPROTECTION AND PROTECTION AGAINST INFECTION

Legitimate concerns exist about the final antibody level attained with a two-dose regimen, which is typically lower than that attained with a three-dose regimen. As HBV antibody levels decline with time, lower final antibody levels theoretically increase the risk of losing seroprotection. Study of vaccine efficacy has defined seroprotection as antibody levels greater than or equal to 10 mIU/mL.11 Yet evidence suggests that even when antibody levels drop below this level, the risk of symptomatic HBV infection does not increase. Evidence also suggests that immune memory outlasts the presence of seroprotective antibody levels, indicating that true protection against significant infection does not necessarily correlate with, and may even exceed, seroprotection.2 This may relate to HBV’s long incubation period, which allows memory cells time to generate an effective immune response.10 For example, Floreani et al12 showed that even though 15% of adults lost seroprotective antibody levels 10 years after vaccination, none demonstrated hepatitis B antigen reactivity or seroconversion.

POSTVACCINATION TESTING AND ADDITIONAL DOSES

At times, it may be wise to measure antibody levels after the final dose to confirm seroprotection. Seroprotection should be documented when knowledge of the patient’s immune status will affect subsequent management. As recommended by the US Centers for Disease Control and Prevention, health care workers, hemodialysis patients, immunocompromised patients, and sexual partners of patients with chronic HBV infection should undergo antibody testing 1 to 2 months after the completion of a three-dose vaccination regimen. Hemodialysis patients require annual confirmation of seroprotection and should receive booster doses of HBV vaccine if necessary.

Postvaccination testing (quantitative HBV surface antibody testing) costs about the same as a single dose of HBV vaccine. Therefore, if postvaccination testing is considered because of missed vaccine doses, it may be more cost-efficient to simply administer the missed dose.

References
  1. Department of Health and Human Services. Appendix A Immunization Management Issues. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5516a2.htm. Accessed April 6, 2014.
  2. Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis 2011; 53:68–75.
  3. Scolnick EM, McLean AA, West DJ, McAleer WJ, Miller WJ, Buynak EB. Clinical evaluation in healthy adults of a hepatitis B vaccine made by recombinant DNA. JAMA 1984; 251:2812–2815.
  4. Merck and Co, Inc. 1998. Recombivax HB. http://www.merck.com/product/usa/pi_circulars/r/recombivax_hb/re-combivax_pi.pdf. Accessed April 7, 2014.
  5. Marsano LS, West DJ, Chan I, et al. A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults. Vaccine 1998; 16:624–629.
  6. Cassidy WM, Watson B, Ioli VA, Williams K, Bird S, West DJ. A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatrics 2001; 107:626–631.
  7. Van Damme P, Moiseeva A, Marichev I, et al. Five years follow-up following two or three doses of a hepatitis B vaccine in adolescents aged 11–15 years: a randomised controlled study. BMC Infect Dis 2010; 10:357.
  8. Heron L, Selnikova O, Moiseieva A, et al. Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11–15 years: a randomised controlled trial. Vaccine 2007; 25:2817–2822.
  9. Heron LG, Chant KG, Jalaludin BB. A novel hepatitis B vaccination regimen for adolescents: two doses 12 months apart. Vaccine 2002; 20:3472–3476.
  10. Jackson Y, Chappuis F, Mezger N, Kanappa K, Loutan L. High immunogenicity of delayed third dose of hepatitis B vaccine in travellers. Vaccine 2007; 25:3482–3484.
  11. Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis 1999; 179:489–492.
  12. Floreani A, Baldo V, Cristofoletti M, et al. Long-term persistence of anti-HBs after vaccination against HBV: an 18 year experience in health care workers. Vaccine 2004; 22:607–610.
References
  1. Department of Health and Human Services. Appendix A Immunization Management Issues. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5516a2.htm. Accessed April 6, 2014.
  2. Leuridan E, Van Damme P. Hepatitis B and the need for a booster dose. Clin Infect Dis 2011; 53:68–75.
  3. Scolnick EM, McLean AA, West DJ, McAleer WJ, Miller WJ, Buynak EB. Clinical evaluation in healthy adults of a hepatitis B vaccine made by recombinant DNA. JAMA 1984; 251:2812–2815.
  4. Merck and Co, Inc. 1998. Recombivax HB. http://www.merck.com/product/usa/pi_circulars/r/recombivax_hb/re-combivax_pi.pdf. Accessed April 7, 2014.
  5. Marsano LS, West DJ, Chan I, et al. A two-dose hepatitis B vaccine regimen: proof of priming and memory responses in young adults. Vaccine 1998; 16:624–629.
  6. Cassidy WM, Watson B, Ioli VA, Williams K, Bird S, West DJ. A randomized trial of alternative two- and three-dose hepatitis B vaccination regimens in adolescents: antibody responses, safety, and immunologic memory. Pediatrics 2001; 107:626–631.
  7. Van Damme P, Moiseeva A, Marichev I, et al. Five years follow-up following two or three doses of a hepatitis B vaccine in adolescents aged 11–15 years: a randomised controlled study. BMC Infect Dis 2010; 10:357.
  8. Heron L, Selnikova O, Moiseieva A, et al. Immunogenicity, reactogenicity and safety of two-dose versus three-dose (standard care) hepatitis B immunisation of healthy adolescents aged 11–15 years: a randomised controlled trial. Vaccine 2007; 25:2817–2822.
  9. Heron LG, Chant KG, Jalaludin BB. A novel hepatitis B vaccination regimen for adolescents: two doses 12 months apart. Vaccine 2002; 20:3472–3476.
  10. Jackson Y, Chappuis F, Mezger N, Kanappa K, Loutan L. High immunogenicity of delayed third dose of hepatitis B vaccine in travellers. Vaccine 2007; 25:3482–3484.
  11. Jack AD, Hall AJ, Maine N, Mendy M, Whittle HC. What level of hepatitis B antibody is protective? J Infect Dis 1999; 179:489–492.
  12. Floreani A, Baldo V, Cristofoletti M, et al. Long-term persistence of anti-HBs after vaccination against HBV: an 18 year experience in health care workers. Vaccine 2004; 22:607–610.
Issue
Cleveland Clinic Journal of Medicine - 81(6)
Issue
Cleveland Clinic Journal of Medicine - 81(6)
Page Number
346-348
Page Number
346-348
Publications
Cleveland Clinic Journal of Medicine
Publications
Cleveland Clinic Journal of Medicine
Topics
Adolescent Medicine
Infectious Diseases
Men's Health
Women's Health
Vaccines
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Do patients who received only two doses of hepatitis B vaccine need a booster?
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