Pharmaceutical Manufacturing Handbook: Production and

TABLE 5 Continued
Delivery
System/Adjuvant
HBcAg
Cholera toxin
REFERENCES 637
available today, which are administered intramuscularly or subcutaneously, involve
alum as an adjuvant. The drive for initiating further research into vaccine adjuvants
has been stimulated by many factors, among the chief of which is that the aluminum -
based adjuvants currently available have failed in many candidate vaccines or have
not achieved the necessary immunity or induced a cytotoxic T - cell response. Nasally
formulated vaccines, mainly subunit vaccines, currently being purifi ed are less immunogenic
and also cannot elicit the necessary T - cell response. As a result, research is
now focusing on fi nding newer adjuvants for nasal DNA and subunit vaccines in
order to attain specifi c immune responses as well as the necessary antibody subtype
response. In addition to this, an adjuvant can help to reduce the dose of antigen
required and also the number of doses needed to achieve mucosal immunity [203 –
207] . Despite the extensive research going on in the fi eld of vaccine adjuvants, the
only FDA - approved adjuvant for human use is alum. There are several other adjuvants,
such as monophosphoryl lipid A (MPL), that have been approved in the
European market; another, Corixa, is used as an adjuvant in Fendrix, the hepatitis
B vaccine of GlaxoSmithKline Biologicals. The main hindrance to the approval of
many adjuvants that reach clinical trials is their potential to elicit toxic side effects
in clinical use. It has been reported that aluminum salts do induce some allergies in
humans. As more purifi ed and target - oriented or specifi c vaccines obtained by
recombinant technology are being launched, it becomes more diffi cult for vaccine
antigens alone to induce the necessary immune responses, as these recombinant
antigens or synthetic peptides cannot jump start an immune response.
A number of adjuvants are awaiting approval for human use. The main impediment
to the successful development of vaccine adjuvants is that their mechanism of
action is not clearly understood. Table 5 offers a list of available nasal drug delivery
systems and the various adjuvants that have been used in the development of nasal
vaccines.
REFERENCES
Antigen Employed
Remarks
HBsAg
Stimulates strong Th1
response
Group B streptococci High levels of IgA in
cervicovaginal
secretions
Haemophilus infl uenzae Effective nasal
vaccination
Infl uenza virus
—
Synthetic peptide of RSV Complete protection
Reference
1. Southall , J. , and Ellis , C. ( 2000 ), Developments in nasal drug delivery , Innovat. Pharm.
Technol. , 110 – 115 .
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