Biomedical Engineering Reference
In-Depth Information
Box 13.4
Product case study: Engerix B
Engerix B (tradename) is a subunit vaccine containing purifi ed recombinant hepatitis B surface
antigen (HBsAg) that gained approval in the USA in 1998. It is indicated for active immuniza-
tion against infection caused by all known serotypes of hepatitis B virus.
The rHBsAg is produced in an engineered
S. cerevisiae
strain and is likely purifi ed sub-
sequent to fermentation by a procedure somewhat similar to that presented in Figure 13.10.
The fi nal product is presented as a sterile suspension of the antigen absorbed onto aluminium
hydroxide (adjuvant), in either single-use vials or pre-fi lled syringes. It also contains NaCl and
phosphate buffer components as excipients. It is intended for i.m. injection, usually as 10 µg
in a volume of 0.5 ml for infants/children or 20 µg (in 1.0 ml) for adults. The normal dosage
schedule entails initial administration followed by boosters after 1 and 6 months.
The protective effi cacy of Engerix B has been demonstrated in a number of trials, in the
context of infants, children and adults. Seroprotection rates (measured as serum anti-hepatitis
B antibody titres above a value of 10 mIU ml
1
) of over 95 per cent were usually recorded. The
product was found to be generally well tolerated. The most frequently reported adverse effects
were local reactions at the injection sites, fever, headache and dizziness. Special consideration
to risk:benefi t ratio should be given to MS patients, as exacerbations of this condition have
been (rarely) reported following administration of hepatitis B and other vaccines. Engerix B is
manufactured and marketed by GlaxoSmithKline.
strong humoral and, in particular, cell-mediated immunity. The immunological response (espe-
cially the cell-mediated response) to subunit vaccines is usually less pronounced.
Poxviruses and, more specifi cally, the vaccinia virus remain the most thoroughly characterized
vector systems developed. These are large, enveloped double-stranded DNA viruses. They are the
only DNA-containing viruses that replicate in the cytoplasm of infected cells. The most studied
members of this family are variola and vaccinia. The former represents the causative agent of
smallpox, and the latter (being antigenically related to variola but non-pathogenic) was used to
immunize against smallpox. Vaccinia-based vaccination programmes led to the global eradication
of smallpox, fi nally achieved by the early 1980s.
A number of factors render vaccinia virus a particularly attractive vector system. These
include:
•
capacity to assimilate large quantities of DNA in its genome successfully;
•
prior history of widespread and successful use as a vaccination agent;
•
ability to elicit long-lasting immunity;
•
ease of production and low production costs;
•
stability of freeze-dried fi nished vaccine product.
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