Hepatitis B vaccine

Hepatitis B vaccine is a vaccine developed for the prevention of hepatitis B virus infection. The vaccine contains one of the viral envelope proteins, hepatitis B surface antigen (HBsAg). It is produced by yeast cells, into which the genetic code for HBsAg has been inserted. A course of two to three (2â€"3) vaccine injections is given, the second injection at least one month after the first dose and the third injection being administered six months after the first dose. The first and second dose offer complete protection. The final injection (second or third depending on number of vaccines being administered) is to prolong protection against the hepatitis B virus. Afterward an immune system antibody to HBsAg is established in the bloodstream. The antibody is known as anti-HBs. This antibody and immune system memory then provide immunity to hepatitis B infection. The first vaccine became available in 1981.

A range of vaccines is available in the market. Presently recombinant DNA vaccines are available, which means they are produced by inserting the gene for HBV into common baker's yeast where it is grown, harvested, and purified. HBV infection cannot occur from receiving hepatitis B vaccine. The common brands available are Recombivax HB (Merck), Engerix-B (GSK), Elovac B (Human Biologicals Institute, a division of Indian Immunologicals Limited), Genevac B (Serum Institute), Shanvac B, etc. These vaccines are given intramuscularly.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.

Medical uses

Babies born to mothers who've had the hepatitis virus are vaccinated with hepatitis B vaccine and injected with hepatitis B immunoglobulin (HBIG).

Many countries now routinely vaccinate infants against hepatitis B. In countries with high rates of hepatitis B infection, vaccination of newborns has not only reduced the risk of infection, but has also led to marked reduction in liver cancer. This was reported in Taiwan where the implementation of a nationwide hepatitis B vaccination program in 1984 was associated with a decline in the incidence of childhood hepatocellular carcinoma.

In the UK, the vaccine is offered to MSM, usually as part of a sexual health check-up. A similar situation is in operation in Ireland.

In many areas, vaccination against hepatitis B is also required for all health-care and laboratory staff.

The Centers for Disease Control and Prevention have issued recommendations for vaccination against hepatitis B among patients with diabetes mellitus.

Effectiveness

Following the primary course of 3 vaccinations, a blood test may be taken after an interval of 1â€"4 months to establish if there has been an adequate response, which is defined as an anti-hepatitis B surface antigen (anti-Hbs) antibody level above 100 mIU/ml. Such a full response occurs in about 85â€"90% of individuals.

An antibody level between 10 and 100 mIU/ml is considered a poor response, and these people should receive a single booster vaccination at this time, but do not need further retesting.

People who fail to respond (anti-Hbs antibody level below 10 mIU/ml) should be tested to exclude current or past Hepatitis B infection, and given a repeat course of 3 vaccinations, followed by further retesting 1â€"4 months after the second course. Those who still do not respond to a second course of vaccination may respond to intradermal administration or to a high dose vaccine or to a double dose of a combined Hepatitis A and B vaccine. Those who still fail to respond will require hepatitis B immunoglobulin (HBIG) if later exposed to the hepatitis B virus.

Poor responses are mostly associated with being over the age of 40 years, obesity and smoking, and also in alcoholics, especially if with advanced liver disease. Patients who are immunosuppressed or on renal dialysis may respond less well and require larger or more frequent doses of vaccine. At least one study suggests that hepatitis B vaccination is less effective in patients with HIV.

Duration of protection

It is now believed that the hepatitis B vaccine provides indefinite protection. However, it was previously believed and suggested that the vaccination would only provide effective cover of between five and seven years, but subsequently it has been appreciated that long-term immunity derives from immunological memory which outlasts the loss of antibody levels and hence subsequent testing and administration of booster doses is not required in successfully vaccinated immunocompetent individuals. Hence with the passage of time and longer experience, protection has been shown for at least 25 years in those who showed an adequate initial response to the primary course of vaccinations, and UK guidelines now suggest that for initial responders who require ongoing protection, such as for healthcare workers, only a single booster is advocated at 5 years.

Safety

Several studies looked for a significant association between recombinant hepatitis B vaccine (HBV) and multiple sclerosis (MS) in adults. Most published scientific studies do not support a causal relationship between hepatitis B vaccination and demyelinating diseases such as MS. A 2004 study reported a significant increase in risk within 3 years of vaccination. Some of these studies were criticized for methodological problems. This controversy created public misgivings about HB vaccination, and hepatitis B vaccination in children remained low in several countries. A 2006 study concluded that evidence did not support an association between HB vaccination and sudden infant death syndrome, chronic fatigue syndrome, or multiple sclerosis. A 2007 study found that the vaccination does not seem to increase the risk of a first episode of MS in childhood.

A 2009 study of the hepatitis B vaccine and associated risk of CNS inflammatory demyelination was conducted. The hepatitis B vaccine was found to be generally safe, however the Engerix B vaccine appeared to triple the risk of CNS inflammatory demyelination in infant boys. The study was criticized for methodological errors.

The World Health Organization recommends a pentavalent vaccine, combining vaccines against diphtheria, tetanus, pertussis and Haemophilus influenzae type B with the vaccine against hepatitis B. There is not yet sufficient evidence on how effective this pentavalent vaccine is in relation to the individual vaccines.

History

The invention of the vaccine began with the realization (by virologist Alfred Prince, in 1968) that the Australia antigen was part of a virus that caused hepatitis B. Maurice Hilleman at Merck used three treatments (pepsin, urea and formaldehyde) of blood serum together with rigorous filtration to yield a product that could be used as a safe vaccine. Hilleman hypothesized that he could make an HBV vaccine by injecting patients with hepatitis B surface protein. In theory, this would be very safe, as these excess surface proteins lacked infectious viral DNA. The immune system, recognizing the surface proteins as foreign, would manufacture specially shaped antibodies, custom-made to bind to, and destroy, these proteins. Then, in the future, if the patient were infected with hepatitis B virus, the immune system could promptly deploy protective antibodies, destroying the viruses before they could do any harm.

Hilleman collected blood from gay men and intravenous drug usersâ€"groups known to be at risk for HBV infections. This was in the late 1970s, when HIV was yet unknown to medicine. In addition to the sought-after hepatitis B surface proteins, the blood samples likely contained HIV. Hilleman devised a multistep process to purify this blood so that only the hepatitis B surface proteins remained. Every known virus was killed by this process, and Hilleman was confident that the vaccine was safe.

The first large-scale trials for the blood-derived vaccine were performed on gay men, considered to be an at-risk group. Later, Hilleman’s vaccine was falsely blamed for igniting the AIDS epidemic. (See Wolf Szmuness.) But, although the purified blood vaccine seemed questionable, it was determined to have indeed been free of HIV. The purification process had destroyed all virusesâ€"including HIV. The vaccine was approved in 1981.

It was withdrawn from the marketplace when Pablo DT Valenzuela, Research Director of Chiron Corporation succeeded in 1986 in making the antigen in yeast and invented the first recombinant vaccine. The recombinant vaccine was developed by inserting the HBV gene that codes for the surface protein into a species of yeast called Saccharomyces cerevisiae. This allows the yeast to produce only the noninfectious surface protein, without any danger of introducing actual viral DNA into the final product. This is the vaccine still in use today.

The Future of Hepatitis B Vaccines

Injectable Hepatitis B vaccines require expensive production processes and refrigeration, which can make them difficult to access in developing countries. As a result, researchers have been working to engineer plants to produce Hepatitis B vaccines, so that people can eat these plants to receive the vaccine. Potatoes, bananas, lettuce, carrots, tobacco are some of the plants being genetically engineered produce the Hepatitis B vaccine.

The process of genetically engineering plants to produce the vaccine includes extracting the gene that codes for Hepatitis B surface antigens from the Hepatitis B genome, and placing it in a bacterial plasmid. The bacteria then infect a plant, which will produce the surface antigens. When a human eats the plant, their body is stimulated to produce an antibody response to the surface antigens. Although concerns remain in improving the efficacy of edible vaccines, controlling the dosage of vaccine in each plant, and managing land allocation for this process, scientists consider this a promising avenue for vaccinating underprivileged areas of the world.

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