Antibody Levels and Protection after Hepatitis B Vaccination: Results of a 15-Year Follow-up

McMahon, Brian J. MD
Bruden, Dana L. MS
Petersen, Kenneth M. MD
Bulkow, Lisa R. MS
Parkinson, Alan J. PhD
Nainan, Omana PhD
Khristova, Marina PhD, DSc
Zanis, Carolyn BS
Peters, Helen BS
Margolis, Harold S. MD

From Arctic Investigations Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, and the Alaska Native Medical Center, Anchorage, Alaska; and the Centers for Disease Control and Prevention, Atlanta, Georgia.
Current author addresses and author contributions are available at www.annals.org.

For author affiliations, see end of text.

Acknowledgments: The authors acknowledge the support they received from the many Community Health Aides in the study villages and the nurses at the Arctic Investigations Program and the Alaska Native Medical Center who over the years gave their valuable time to the study.

Grant Support: Partial support through the Alaska Native Tribal Health Consortium from the Division of Viral Hepatitis, National Centers for Infectious Diseases, Centers for Disease Control and Prevention Cooperative Agreement CA #U50/CCU022279. Merck & Co., Inc., West Point, Pennsylvania, supplied the vaccine and partially funded transportation during the first 10 years of follow-up through an unrestricted grant.

Potential Financial Conflicts of Interest:Grants received: B.J. McMahon (Merck Pharmaceuticals); Stock ownership or options (other than mutual funds): A.J. Parkinson (Merck & Co., Inc.).

Requests for Single Reprints: Brian J. McMahon, MD, Arctic Investigations Program, Centers for Disease Control and Prevention, 4055 Tudor Center Drive, Anchorage, AK 99508; e-mail, [email protected].

Current author addresses and author contributions are available at www.annals.org.

Current Author Addresses: Dr. McMahon, Ms. Bruden, Ms. Bulkow, Dr. Parkinson, Ms. Zanis, and Ms. Peters: Arctic Investigations Program, Centers for Disease Control and Prevention, 4055 Tudor Center Drive, Anchorage, AK 99508.

Dr. Peterson: 13101 Floral Lane, Anchorage, AK 99516.

Drs. Nainan, Khristova, and Margolis: Viral Hepatitis Division, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA 30333.

Author Contributions: Conception and design: B.J. McMahon, L.R. Bulkow, A.J. Parkinson.

Analysis and interpretation of the data: B.J. McMahon, D.L. Bruden, K.M. Petersen, L.R. Bulkow, M. Khristova.

Drafting of the article: B.J. McMahon, A.J. Parkinson, O. Nainan, M. Khristova.

Critical revision of the article for important intellectual content: B.J. McMahon, D.L. Bruden, K.M. Petersen, L.R. Bulkow, O. Nainan, H.S. Margolis.

Final approval of the article: B.J. McMahon, A.J. Parkinson, C. Zanis, H.V. Peters, H.S. Margolis.

Provision of study materials: K.M. Petersen, C. Zanis, H.V. Peters.

Statistical expertise: D.L. Bruden, L.R. Bulkow.

Obtaining of funding: H.S. Margolis.

Administrative, technical, or logistic support: O. Nainan, H.S. Margolis.

Collection and assembly of data: O. Nainan, M. Khristova, C. Zanis, H.V. Peters, H.S. Margolis.

Annals of Internal Medicine 142(5):p 333-341, March 1, 2005.

Background:

The duration of protection afforded by hepatitis B vaccination is unknown.

Objective:

To determine antibody persistence and protection from hepatitis B virus (HBV) infection.

Design:

Prospective cohort study.

Setting:

15 villages in southwest Alaska.

Participants:

1578 Alaska Natives vaccinated at age 6 months or older.

Intervention:

During 1981–1982, participants received 3 doses of plasma-derived hepatitis B vaccine. This cohort was followed annually over the first 11 years, and 841 (53%) persons were tested at 15 years.

Measurements:

Antibody to hepatitis B surface antigen (anti-HBs), markers of HBV infection, and testing to identify HBV variants.

Results:

Levels of anti-HBs in the cohort decreased from a geometric mean concentration of 822 mIU/mL after vaccination to 27 mIU/mL at 15 years. Initial anti-HBs level, older age at vaccination, and male sex were associated with persistence of higher anti-HBs levels at 15 years when analyzed by a longitudinal linear mixed model. After adjustment for initial anti-HBs level and sex, those vaccinated at age 6 months to 4 years had the lowest anti-HBs level at 15 years. Asymptomatic breakthrough infections were detected in 16 participants and occurred more frequently in persons who did not respond to vaccination than those who responded (P = 0.01). Among infected persons with viremia, 2 were infected with wild-type HBV and 4 had HBV surface glycoprotein variants, generally accompanied by wild-type HBV.

Limitations:

The loss of participants to follow-up at 15 years was 47%. However, characteristics of persons tested were similar to those of persons lost to follow-up.

Conclusions:

Hepatitis B vaccination strongly protected against infection for at least 15 years in all age groups. Antibody levels decreased the most among persons immunized at 4 years of age or younger.