Hepatitis B Virus Immunity 15 Years After Vaccination: Implications for Young Adults
ABSTRACT: In 2014, an estimated 19,200 persons in the United States were newly infected with hepatitis B virus (HBV). While the rate of new infections has declined steeply since the implementation of a national HBV vaccination program, HBV continues to represent a potentially serious health threat. The HBV vaccination schedule most often used for children and adults is 3 intramuscular injections, with the second and third doses administered 1 month and 6 months, respectively, after the first dose. In this retrospective chart review, 256 graduate students entering a physician assistant program at a suburban Philadelphia university had their hepatitis B surface antibody levels evaluated for positive immune responses. The resulting data suggest waning immunity 15 years after completing the primary HBV vaccination series.
KEYWORDS: Hepatitis B virus, hepatitis B vaccine, hepatitis B surface antibodies, vaccine booster, immunity, titers, seroprotection
In 2014, a total of 2953 cases of acute hepatitis B virus (HBV) infection were reported to the Centers for Disease Control and Prevention in the United States, and the reported overall incidence of acute HBV that year was 0.9 cases per 100,000 US population.1 However, because many HBV infections either go undiagnosed or are never reported, the actual number of new infections is estimated to be approximately 10-fold higher.1
In 2014, an estimated 19,200 persons in the United States were newly infected with HBV.1 Rates of infection are highest among adults.2 The rate of new HBV infections has declined by approximately 82% since 1991, when a national strategy to eliminate HBV infection was implemented in the United States.1 The decline in HBV infection has been greatest among children born since 1991, when routine vaccination of children was first recommended.1
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In highly endemic areas, HBV is most commonly spread in the following ways3:
- From mother to child at birth (perinatal transmission). The development of chronic infection is very common in infants infected by way of their mothers or before the age of 5 years.
- Through horizontal transmission (exposure to infected blood), especially from an infected child to an uninfected child during the first 5 years of life.
- Through percutaneous or mucosal exposure to infected blood, as well as through saliva and menstrual, vaginal, and seminal fluids.
- Through sexual transmission, particularly in unvaccinated men who have sex with men and in heterosexual persons with multiple sex partners or contact with sex workers. Infection in adulthood leads to chronic hepatitis in less than 5% of cases.
- Through reuse of needles and syringes either in health care settings or among persons who inject drugs.
- During medical, surgical, and dental procedures and tattooing, or through the use of razors and similar objects that have been contaminated with infected blood.
The HBV vaccination schedule most often used for children and adults is 3 intramuscular injections, with the second and third doses administered 1 month and 6 months, respectively, after the first dose. Alternative schedules have been approved for certain vaccines and certain patient populations.1
While the results of published studies conflict, the consensus is that HBV vaccination confers long-term protection against clinical illness and chronic HBV infection. Some research has indicated that 15 years after HBV vaccination, fewer than half of recipients in 2 rural Gambian villages had detectable hepatitis B surface antibodies (anti-HBs)4; moreover, the prevalence of HBV carriage in the unvaccinated population was found to be similar to the prevalence 20 years earlier.4 Another study by researchers affiliated with the World Health Organization Collaborating Centre for Prevention and Control of Viral Hepatitis suggested that despite antibody decline or loss, immune memory exhibits long-term persistence.5 A study by Simons and colleagues6 indicated that despite low anti-HBs levels, participants in Alaska tested positive for tumor necrosis factor α, interleukin 10, or interleukin 6 production by HBV surface antigen–specific T cells, indicating long-lasting cellular immunity of at least 32 years. And, a study by Zanetti and colleagues7 showed that immunologic memory remained intact for at least 20 years among healthy vaccinated individuals in Italy who initiated the HBV vaccination schedule after 6 months of age.
Van Der Meeren and colleagues8 administered a challenge dose to adolescents aged 15 to 16 years in Germany who had completed the HBV vaccination series before 18 months of age. Before the challenge dose, only 65.4% of participants were seroprotected, but one month after the challenge dose, 97.9% were seroprotected. The authors concluded that HBV immunity persists after 15 to 16 years after primary vaccination.
Conflicting reports in the literature include a 15-year follow-up study9 regarding protection of the HBV vaccine administered beginning at birth, the results of which indicated that 15 years later, only 8% of participants in Micronesia had past HBV infection but not chronic infection, and an absence of immune response to an additional vaccine dose seen in half of the participants might indicate waning immunity.
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The purpose of this study was to evaluate whether students need a booster of HBV vaccine. Greater potential exposure to HBV—resulting from such factors as an increase in the number of people obtaining tattoos and body piercings, “adventure travel,” opportunities for health care students to spend spring break providing medical care to an underserved population, and opportunities to study abroad—is increasing the need for assured HBV vaccination coverage. For example, in 2015, approximately 3 in 10 Americans (29%) had at least one tattoo, up from roughly 2 in 10 (21%) in 2012.10 According to a 2010 poll, nearly 1 in 4 US persons have a piercing in some place other than an earlobe.11 Adventure travel—tourism involving exploration or travel with perceived or actual risk that may require specialized skills and physical exertion—has grown in the United States at an annual rate of 65% since 2009.12
We performed a retrospective chart review of 256 college graduate students (215 women, 41 men; age range, 23 to 65 years; mean age, 27 years) entering the physician assistant program at Arcadia University in Glenside, Pennsylvania, a suburb of Philadelphia. These students required HBV titers drawn for entrance into their program. We reviewed each student’s date of birth; date of HBV vaccine injections 1, 2, and 3; date and value of the HPV titer drawn; and therapeutic antibody response.
Mann-Whitney test results revealed statistically significant differences (P = .001) in the number of years since completion of the HBV vaccination series between participants who had therapeutic levels of anti-HBs and those who did not. As seen in Figure 1 and Table 1, the students with therapeutic levels had received their final injection of the vaccination series an average of 14.7 years prior, while students who were no longer at therapeutic levels had received their final injection an average of 17.3 years prior.
Figure 1. Average number of years since HBV vaccine series completion in a cohort of 256 graduate students.
The results of chi-square tests of homogeneity between groups revealed statistically significant differences in the number of individuals at therapeutic levels between the group that had received the final injection within 15 years and the group that had received it more than 15 years prior. As seen in Figure 2 and Table 2, 83% of participants who had completed the vaccination series within 15 years were at therapeutic levels, compared with 67% of participants who had completed the series longer than 15 years previously.
Figure 2. Percentage of a cohort of 256 graduate students based on years since HBV vaccine series completion.
These study results suggest that there may be a need to have a universal booster approximately 15 years after completion of the initial childhood series of HBV immunizations.
Immune memory was demonstrated in only 67% of our population 15 years after vaccination series completion. These data suggest that administering a booster dose of HBV during the typical person’s college years may be more effective in protecting the population against a disease that is acquired mainly through adult behaviors, including sexual activity, tattooing, body piercing, medical mission travel, study abroad, and adventure travel. Additionally, health care professional students must be able to “prove immunity” with positive HBV titer test results in order to complete their education and clinical requirements. More clinical studies need to be completed to ascertain at what point after vaccination HBV antibody protection wanes.
Theresa M. Smith, MSN, FNP-BC, is a nurse practitioner in the Student Health Services Department at Arcadia University in Glenside, Pennsylvania.
Kathy McGovern, MSN, FNP-BC, is the director of the Student Health Services Department at Arcadia University in Glenside, Pennsylvania.
Alexa Mojica, BA, MPH, is a graduate of the Arcadia University Public Health Program and works at Fox Chase Cancer Center in Philadelphia, Pennsylvania.
Anand Bhattacharya, MHS, is a data scientist in nursing translational research at the Hospital of the University of Pennsylvania in Philadelphia.
- Hepatitis B FAQs for health professionals. Centers for Disease Control and Prevention website. http://www.cdc.gov/hepatitis/hbv/hbvfaq.htm. Updated August 4, 2016. Accessed August 15, 2016.
- Daniels D, Grytdal S, Wasley A; Centers for Disease Control and Prevention (CDC). Surveillance for acute viral hepatitis—United States, 2007. MMWR Surveill Summ. 2009;58(3):1-27.
- Hepatitis B fact sheet. World Health Organization website. http://www.who.int/mediacentre/factsheets/fs204/en/. Updated July 2016. Accessed August 15, 2016.
- van der Sande MAB, Waight P, Mendy M, et al. Long-term protection against carriage of hepatitis B virus after infant vaccination. J Infect Dis. 2006;193(11):1528-1535.
- Van Damme P, Van Herck K. A review of the long-term protection after hepatitis A and B vaccination. Travel Med Infect Dis. 2007;5(2):79-84.
- Simons BC, Spradling PR, Bruden DJT, et al. A longitudinal hepatitis B vaccine cohort demonstrates long-lasting hepatitis B virus (HBV) cellular immunity despite loss of antibody against HBV surface antigen. J Infect Dis. 2016;214(2):273-280.
- Zanetti AR, Mariano A, Romanò, L, et al; Study Group. Long-term immunogenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study. Lancet. 2005;366(9494):1379-1384.
- Van Der Meeren, Behre U, Crasta P. Immunity to hepatitis B persists in adolescents 15-16 years of age vaccinated in infancy with three doses of hepatitis B vaccine. Vaccine. 2016;34(24):2745-2749.
- Bialek SR, Bower WA, Novak R, et al. Persistence of protection against hepatitis B virus infection among adolescents vaccinated with recombinant hepatitis B vaccine beginning at birth: a 15-year follow-up study. Pediatr Infect Dis J. 2008;27(10):881-885.
- Shannon-Missal L. Tattoo takeover: three in ten Americans have tattoos, and most don’t stop at just one. The Harris Poll. http://www.theharrispoll.com/health-and-life/Tattoo_Takeover.html. Published February 10, 2016. Accessed August 25, 2016.
- Millennials: Portrait of Generation Next: Confident. Connected. Open to Change. Pew Research Center. http://www.pewsocialtrends.org/files/2010/10/millennials-confident-connected-open-to-change.pdf. Published February 2010. Accessed August 25, 2016.
- Hanisko C. New adventure tourism report reveals $263B market, up 65% per annum since 2009. Adventure Travel News. http://www.adventuretravelnews.com/new-adventure-tourism-report-reveals-263b-market-up-65-per-annum-since-2009. Published September 10, 2013. Accessed August 25, 2016.