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.
CKD is graded in five stages, with Stage 1 being the mildest and Stage 5 being the most severe. Stage 5 is classified as end-stage renal disease. The number of patients enrolled in the ESRD Medicare-funded program has increased from approximately 10,000 beneficiaries in 1973 to 661,648 as of 2013. There are approximately 21,000 new cases per year.
In order to clear patients’ bodies of blood waste, many patients are required to be on dialysis, a process that involves filtering blood through external machines. Unfortunately, the kidneys of patients with ESRD are irreversibly damaged and a kidney transplant is required to restore function. In 2013, 400,000+ ESRD patients were receiving chronic dialysis. Patients with ESRD are at an increased risk of mortality. Five-year survival probabilities for dialysis patients are between 35% and 40%.
Many dialysis patients are required to take immunosuppressive treatments, which lower their natural immune response, increasing susceptibility to infection. According to some estimates, if a patient with ESRD is newly infected with HBV, the likelihood of that individual developing chronic hepatitis B is between 30% and 60%. Chronic hepatitis B is dangerous and can lead to cirrhosis, hepatocellular carcinoma, and death.
Active vaccination is one of the most crucial precautions to prevent the spread of HBV among patients with ESRD. However, current vaccination options may provide limited seroprotection (a sufficient antibody response capable of preventing infection).
- Patients with ESRD have a poor response to conventional hepatitis B vaccination: Patients with chronic renal failure have lower seroprotection rates after vaccination.
- The severity of chronic renal failure determines the rate of successful seroconversion: Patients with more severe ESRD have lower responses to vaccination. In studies involving a second-generation hepatitis B vaccine used in the U.S., researchers looked at patients with mild, moderate, and severe kidney failure. Analysis showed that in moderate cases of kidney failure, seroprotection dropped to ranges between 66% and 77%. In severe cases, the response rate was further reduced.
- Vaccine effectiveness decreases as patients with ESRD age: In a meta-analysis of 17 clinical studies (1,800 unique patients), there was a significantly decreased response to the hepatitis B vaccine among older dialysis patients.
- Patients with Diabetes Mellitus and in ESRD show markedly decreased seroprotection: Diabetic nephropathy, characterized by damage to the kidneys due to high blood sugar levels, is one of the leading causes of chronic kidney disease. Compared to non-diabetic patients, diabetic patients with normal renal kidney function show a lower seroprotection rate after hepatitis B vaccination. Researchers have also shown that diabetes significantly decreases the seroprotection rate of the hepatitis B vaccine in CKD patients. In one meta-analysis of over 15,000 CKD patients, researchers found that odds of seroprotection in patients with diabetes mellitus was 0.42 times less than the odds of seroprotection in patients without diabetes.
In order to increase seroprotection rates for ESRD patients, various strategies have been researched including augmented dosing schedules, intradermal inoculation, early vaccination, and recombinant third-generation vaccines.
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.