Hepatitis B is described in Chapter 3. Immunization for hepati- tis B became a reality in 1981 when the plasma-derived vac- cine was licensed in the United States. This vaccine was highly effective in inducing immunity, but was associated with sev- eral drawbacks. The supply of suitable carrier plasma needed to make the vaccine was not sufﬁcient for large-scale produc- tion. Also, despite the chemical treatment of plasma products for safety, there was some concern about the risk, albeit small, of HIV transmission (131). Both of these issues were addressed in 1986, when the yeast recombinant hepatitis B vaccine was licensed. This particular vaccine has been a major breakthrough for the ﬁeld of medicine. It was the ﬁrst licensed recombinant viral vaccine prototype, as well as the ﬁrst effective viral vaccine for a sexually transmitted disease. This vaccine is produced by recombinant DNA technology, which inserts the gene for HBsAg (hepatitis B surface antigen) into the yeast Saccharomyces cerevisiae (baker’s yeast). Clinical studies in high-risk homosexual men demonstrated three- dose vaccine efﬁcacy of 82–93% in preventing acute hepatitis B (132,133). Overall, approximately 5% of immunocompetent adults fail to develop signiﬁcant antibody titers after hepatitis B vaccination. Nearly 99% of children respond to vaccination (134), while only 50–70% of those over age 60 acquire immu- nity (135,136). Variables associated with a lower likelihood of seroconversion include immunosuppression, renal failure, prematurity with low birth weight, age older than 40 years, obesity, and smoking (137–139). Because of the decreased rates of seroconversion in speciﬁc populations, additional research is focusing on methods of increasing immunogenicity to hepatitis B vaccines. Alternative delivery systems, such as adenoviruses and vaccinia vectors, are under evaluation. Clinical trials are currently investigating the addition of adju- vants to the current recombinant vaccine in order to increase the host immune response (140,141). Several different types of vaccines are also in development, such as DNA vaccines (142) and Pre-S vaccines (143–145).
The duration of immunity afforded by vaccination merits further long-term studies, but according to present data, long- term efﬁcacy is expected (139). Antibody levels decline rapidly in the ﬁrst year after vaccination, and then level off to a slow pace of decline (146). The loss of detectable antibodies to hep- atitis B years after vaccination does not necessarily indicate a lack of immunity. The majority of individuals are protected by immunological memory in B lymphocytes, which mount an anamnestic response to natural infection (147). Rare cases of hepatitis B infection in previously vaccinated patients have been described (148,149). These patients generally have sub- clinical disease, and none have developed chronic infection or serious complications (139).
The regimen for immunization includes three doses, given at months 0, 1, and 6. Hepatitis B vaccination is recom- mended for adults at risk (i.e., persons living in or traveling to areas of high endemicity of hepatitis B, health-care personnel, morticians, persons engaging in high risk sexual activity, persons with chronic liver disease due to causes other than hepatitis B, prisoners, users of illicit injectable drugs, and police and ﬁre department personnel who render ﬁrst aid) and all children aged 0–18 years. Because of the current wide- spread use in children, a thimerosal-free vaccine was recently approved by the FDA. Thimerosal is a mercury-containing preservative, which has prompted the limitation of its use in children (150). In persons in whom vaccine-induced protection is less complete, such as in hemodialysis patients, the need for a booster dose should be assessed by annual antibody testing.
Adverse effects after hepatitis B vaccination are generally mild and well-tolerated.
Fatigue. Fatigue is most commonly reported (15%). Headache. Headache occurs in 9% of subjects. Fever. Fever occurs in 1–9% of vaccinees (151,152).
A post-marketing clinical surveillance of 4.5 million doses of hepatitis B vaccine over 5 years revealed no serious or severe reactions attributable to the vaccine (153).
Rarely occurring adverse effects include:
Thrombocytopenic purpura (154–156).
Vasculitis (157,158). Rheumatoid arthritis (159). Lichen planus (160). Lichenoid reaction (161).
However, it appears that these conditions do not occur at a higher rate than in the unvaccinated population. Large- scale hepatitis B vaccination programs have been unable to establish any association between the vaccine and severe adverse effects other than rare episodes of anaphylaxis (152,162).
On May 14, 2000, the FDA announced approval of a new combination vaccine that protects people at least 18 years of age against hepatitis A virus and hepatitis B virus. This vac- cine, Twinrix®, combines two already approved vaccines, Havrix® and Engerix-B®, so that persons at high risk for expo- sure to both viruses can be immunized against both at the same time. The combination reduces the number of injections from 5 to 3.