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The Rationale of Developing a More Immunogenic Hepatitis B Vaccine: Persons of Advanced Age

By December 15, 2016Sci-B-Vac™

Hepatitis B vaccines have been available for more than two decades, but infection with the hepatitis B virus (“HBV”) remains a worldwide health problem. Globally, more than two billion individuals present with serological evidence of HBV infection. Of these, 240 million are chronic carriers and approximately 780,000 hepatitis B-related deaths occur annually.

Second-generation hepatitis B vaccines, which use the HBV surface S antigen to create an immunologic response in vaccine recipients, have been shown to effectively prevent infection in young individuals. Older persons, however, do not respond as well to these currently licensed vaccines. Hepatitis B vaccine failure is often explained by immunosenescence (the gradual deterioration of the immune system brought on by aging), or by immunosuppression, including conditions such as obesity, renal failure, HIV infection, and diabetes.

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Hepatitis B Vaccine Approaches

The immune system becomes less effective as individuals age. Aging is associated with accumulating functional defects at multiple levels of the immune system, which increase susceptibility to infectious diseases, reduce response to vaccination, and increase the risk of developing severe or complicated illnesses as a result of infection.

Second-generation hepatitis B vaccines use an HBV surface antigen, the S antigen, to create an immunologic response in vaccine recipients. While safe, there is an age-specific decline in immune responsiveness to some second-generation hepatitis B vaccines starting around age 40. Early research shows that there is a need to provide a better, more immunogenic hepatitis B vaccine option for aging populations.

Limited effectiveness when administered to older adults

Successful seroprotection (the body’s ability to produce an antibody response capable of preventing an infection) against HBV infection is defined by rate and by an anti-HBV surface antibody (anti-HBs) titer of ≥ 10 mIU/ml following immunization. In one study, researchers aimed to determine the seroprotection rates conferred by a second-generation hepatitis B vaccine administered during an HBV outbreak in an assisted living facility. Researchers found that, of the 48 residents who were eligible for the study, only 33.3% achieved acceptable seroprotection rates. The team determined that age was the only significant determinant of seroprotection. Successful seroprotection rates decreased from 88% among individuals under 60 years of age to 30% and 12% among those aged 80-89 and ≥ 90 years, respectively.

The percent of vaccine non-responders increases with age

The earlier one is inoculated, the better the chance of a successful response. In one meta-analysis that included 21,053 adults across 37 studies, researchers found a significantly decreased response to the hepatitis B vaccine in adults over 40. Compared to individuals under 40, older individuals had a 1.85 increased relative risk of non-response to the hepatitis B vaccine. While immunosenescence starts in early adulthood, it continues to accelerate after 50 to 60 years of age. In a meta-analysis examining one of the most commonly used hepatitis B vaccines in the U.S., researchers examined 11 studies, which included over 2,600 adults. They found that the anti-HBs seroprotection rate remained over 90% for individuals up to 49 years old. However, at age 60 the seroprotection rate dropped to 80% and continued to fall. Individuals vaccinated over the age of 65 had a 65% seroprotection rate. The researchers predicted that less than 50% of individuals in their eighties could maintain a sufficient immune response after receiving the vaccine.

Persons of advanced age are less likely to be vaccinated

Given the importance of early inoculation to reduce the risk of HBV infection, it would benefit adults to be vaccinated as early as possible. However, in the U.S., hepatitis B vaccination coverage is low among adults. A 2013 National Health Interview Survey indicated that only 16.1% of adults aged 50+ had received the recommended three or more doses of a hepatitis B vaccine.

The world population is aging

The global population is aging at an unprecedented rate and the 21st century will witness even more rapid aging than did any century in the past. It is estimated that the proportion of those aged 60+ years will double between 2000 and 2050. This has the potential to nearly double the amount of elderly unvaccinated individuals.

Individuals in Long Term Care (“LTC”) facilities may be at increased risk

Increasingly, families are relying on LTC facilities for elderly care. It is estimated that 70% of individuals turning 65 can expect to use LTC during their lifetime. Between 1998 and 2008, there were over 30 recorded hepatitis B outbreaks in non-hospital health care settings. Given the aging population and growing reliance on LTC facilities, it is becoming increasingly important to protect individuals against HBV transmission.

Comorbidities increase the risk of non-response

Age-related immune defects can be exacerbated by co-existing morbidities and chronic disease. Analysis has shown that non-vaccine response relative risk rates is increased for males, individuals with high BMIs, and smokers. Persons with end-stage renal disease (“ESRD”) and diabetes are at particular risk.

Second-generation HBV vaccines are highly protective against hepatitis B in young individuals. However, as individuals age, the immune system’s capacity to elicit a protective response decreases. The likelihood of success decreases further if you consider other comorbidities such as ESRD and diabetes. Given the aging U.S. population, the increasing number of individuals in long term care facilities, and the low rate of adult hepatitis B vaccination in the U.S., it is becoming increasingly important to develop a hepatitis B vaccine that can induce a more immunogenic response.

Sci-B-Vac™: A Third-Generation Hepatitis B Vaccine

To overcome potential limitations of the second-generation hepatitis B vaccines, VBI developed a third-generation vaccine that contains all three hepatitis B virus surface proteins (S, pre-S1, and pre-S2). By mimicking the hepatitis B virus as it is found in nature, Sci-B-Vac™ may provide more opportunity for the immune system to respond with antibodies that can recognize components of the virus, which may lead to more rapid and potent protective immunity.

To learn more about Sci-B-Vac™, visit: https://www.vbivaccines.com/sci-b-vac/

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