A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

IMMUNOGLOBULINS AS THERAPY 407
DRUGS THAT ENHANCE IMMUNE SYSTEM
FUNCTION
ADJUVANTS
Adjuvants non-specifically augment the immune response
when mixed with antigen or injected into the same site. This is
achieved in the following ways:
• release of the antigen is slowed and exposure to it is
prolonged;
• various immune cells are attracted to the site of injection
and the interaction between such cells is important in
antibody formation.
There are a number of such substances, usually given as
mixtures and often containing lipids, extracts of inactivated
tubercle bacilli and various mineral salts.
IMMUNOSTIMULANTS
Immunostimulants non-specifically enhance immune responses,
examples include bacille Calmette-Guérin (BCG) or killed
Corynebacterium parvum.
INTERLEUKIN-2 (IL-2)
Interleukin-2 is effective treatment for metastatic melanoma
and renal cell carcinoma (Chapter 48).
VACCINES
IMMUNOLOGY AND GENERAL USE
Vaccines stimulate an immune response. They may consist of:
• an attenuated form of the infectious agent, such as the live
vaccines used to prevent rubella, measles or polio, or BCG
to prevent tuberculosis;
• inactivated preparations of virus (e.g. influenza virus) or
bacteria (e.g. typhoid vaccine);
• detoxified exotoxins (‘toxoids’), e.g. tetanus vaccine.
Live vaccine immunization is generally achieved with a single
dose, but three doses are required for oral polio (to cover different
strains). Live vaccine replicates while in the body and
produces protracted immunity, albeit not as long as that
acquired after natural infection. When two live vaccines are
required (and are not in a combined preparation) they may be
given at different sites simultaneously or at an interval of at least
three weeks. Inactivated vaccines usually require sequential
doses of vaccine to produce an adequate antibody response.
Booster injections are required at intervals. The duration of
immunity acquired with the use of inactivated vaccines ranges
from months to years. The vaccination programmes recommended
by the Department of Health (DH) in the UK are
described in detail in a memorandum entitled ‘Immunization
against infectious disease’, available to doctors from the
Department of Health. The British National Formulary summarizes
the recommended schedule of vaccinations.
Contraindications
Postpone vaccination if the patient is suffering from acute illness.
Ensure that the patient is not sensitive to antibiotics used in
the preparation of the vaccine (e.g. neomycin and polymyxin).
Egg sensitivity excludes the administration of several vaccines
(e.g. influenza). Live vaccines should not be given to pregnant
women, nor should they be given to patients who are immunosuppressed.
Live vaccines should be postponed until at least
three months after stopping glucocorticosteroids and six months
after chemotherapy. Live vaccines should not be administered to
HIV-1-positive individuals.
Key points
Vaccine therapy
• Vaccines generally stimulate the production of
protective antibodies or activated T cells.
• Vaccines consist of:
– attenuated infectious agents – antiviral vaccines
(e.g. mumps, rubella, etc.).
– inactivated viral/bacterial preparations (e.g.
influenza virus or typhoid vaccine).
– extracts of detoxified toxins (e.g. tetanus toxin).
• Live vaccines produce protracted immunity and some
(e.g. measles and mumps vaccines) have a low risk of
causing a mild form of the disease.
• Different countries have different vaccination schedules
based on the prevalence of the disease in the
population and the level of herd (‘population’)
immunity.
IMMUNOGLOBULINS AS THERAPY
Immunoglobulin injection gives immediate passive protection
for four to six weeks. Recombinant technology will yield antibodies
of consistent quality in the future, but it is a challenge to
replicate the diversity present in polyclonal human normal
immunoglobulin. Currently, there are two types of immunoglobulin,
namely normal and specific.
HUMAN NORMAL IMMUNOGLOBULIN
Human normal immunoglobulin (HNIG) is prepared from
pooled donations of human plasma. It contains antibodies to
measles, mumps, varicella, hepatitis A and other viruses.
Uses
HNIG is used to protect susceptible subjects from infection
with hepatitis A and measles and, to a lesser extent, to protect
the fetus against rubella in pregnancy when termination is not
an option. Special formulations for intravenous administration
are available for replacement therapy in agammaglobulinaemia,