A Textbook of Clinical Pharmacology and Therapeutics

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-2is 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 sin-
gle dose, but three doses are required for oral polio (to cover dif-
ferent 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 recom-
mended 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 summar-

izes the recommended schedule of vaccinations.

Contraindications

Postpone vaccination if the patient is suffering from acute ill-

ness. Ensure that the patient is not sensitive to antibiotics used in

the preparation of the vaccine (e.g. neomycinandpolymyxin).

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 immuno-

suppressed. 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.

IMMUNOGLOBULINS ASTHERAPY 407

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 anti-

bodies 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 immunoglob-

ulin, 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,