HEPATITIS B VIRUS VACCINE

5 Jun

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

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.

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