Antagonist

Agonist
 PCO 304
IMMUNOPHARMACOLOGY AND INFLAMMATION

By

BEN-AZU Benneth, Ph.D

Email: pharmben4ever@yahoo.com

Department of Pharmacology & Therapeutics,

Faculty of Basic Medical Sciences, CHS, DELSU
 Vaccines and Sera
 Vaccines and sera are biological materials which act by strengthening the
immunological defense of the body against pathogens (mostly infecting organisms
or their toxins).

 Vaccines impart active immunity by acting as antigens which induce production of

specific antibodies by the recipient himself.

 Antisera and Immune globulins impart immunity passively. It is a readymade

antibodies produced by another person or animal who has been actively immunized

 Active immunization is more efficacious and longer lasting than passive

immunization, but the former (vaccine) needs a latent period of one to many weeks,
whereas the latter (antisera) affords immediate protection.

 Antisera are, therefore, curative also, whereas vaccines are only prophylactic.

 Acutely ill, debilitated or immunocompromised individuals may not be able to

generate an adequate antibody response and require passive protection.
 Vaccines
 Vaccines are antigenic materials consisting of the whole microorganism or one of
its products. There are three types of vaccines:

 (i) Killed (Inactivated) vaccines:

 This consist of microorganisms killed by heat or chemicals. They generally require
to be given by a series of injections for primary immunization.

 The immunity is relatively shorter-lasting; booster or maintenance doses are mostly

needed at intervals of months or years.

 (ii) Live attenuated vaccines:

 This consist of live bacteria or viruses which have been rendered avirulent.

 However, they grow and multiply in the body of the host to a limited extent. Live
vaccines usually produced long-lasting immunity.
 Live attenuated vaccines are contraindicated in the following cases with impaired
host defense:
 Leukaemia or other malignancies, especially those receiving cytotoxic
chemotherapy.
 Systemic lupus erythematosus
 Corticosteroid recipients
 AIDS and other immune deficiency states

 This is because the limited virulence of organisms in the live vaccine may be
sufficient to cause a disease

 Two live vaccine should preferably be administered within a gap of 1 month.

 (iii) Toxoids:
 They are modified bacterial exotoxins so that toxicity is lost but antigenicity is
retained. The term ‘vaccine’ is sometimes restricted to preparations of whole
microorganisms and toxoids are enumerated separately.
 Contraindications of Vaccines and Precautionary
Measures To Vaccination
 Vaccination should be deferred in the presence of any acute (especially respiratory)
infection and during pregnancy.

 Antibiotics added during production of vaccines and present in trace amounts in

viral vaccines may cause reaction in individuals sensitive to these.

 Egg proteins (in vaccines prepared on chick embryo) and other materials used for
vaccine culture may be responsible for allergic reactions.

 Adrenaline injection should be available to control allergic reaction to the vaccine,

if it occurs.

 Viral vaccines and toxoids generally afford more prolonged protection than
bacterial vaccines
Classifications of Vaccines
 Bacterial Vaccines
1) Typhoid-Paratyphoid A, B (TAB vaccine)
 It is a sterile suspension, 1 ml containing 1 × 109 S. typhi and 7.5 × 108 each
of S. paratyphi A and B organisms in 5, 10 ml vials.

 Dose - 0.5 mL s.c., 2–3 injections at 2–4 weeks intervals.

 Local tenderness, fever and malaise lasting 1–2 days are common after the
first dose.

 It is estimated to be 70% effective in preventing enteric fever for 1 year.

 Booster doses may be given every 2–3 years

 2) ‘Typhoid-Ty21a’ oral vaccine
 This is a newer live oral typhoid vaccine prepared from Ty 21a attenuated strain of
S. typhi which lacks the Vi polysaccharide and is nonpathogenic.

 The attenuation is due to absence of the enzyme Uridine diphosphate galactose-4

epimerase which is essential for the production of lipopolysaccharide ‘O’ antigens..

 It is avirulent and the efficacy is better than TAB.

 By lodging in the intestinal mucosa, it protects against S. typhi invasion of the gut
in addition to imparting systemic immunity.

 Administered as 3 doses on alternate days in the form of enteric coated capsules

and affords protection for 3 years.

 Side effects are negligible: only 2% cases have reported diarrhoea, abdominal pain
or rashes. It is much more convenient, safer and longer acting.

 It is not approved for use in children below 5 years and in pregnant women.
 3) Cholera vaccine
 It is a suspension of phenol/formalin killed Inaba and Ogawa strains
of V. cholerae, each ml containing 8 × 109 organisms in 5, 10, 30 ml vials.

 Dose: 0.5 ml s.c. or i.m. followed by 1 ml 1–4 weeks later, or a single dose of 1 ml
for mass innoculation.

 Immunity, sufficient to prevent clinical disease, is produced only in 50% of those

innoculated, and lasts 6 months or so sufficient to prevent an epidemic.

 Cholera innoculation during congregations has not reduced the incidence of the
disease (because it takes 2–3 weeks for immunity to develop)

 It also does not prevent carrier state.

 Transient local soreness, low grade fever, aches and pains lasting 1–2 days are
common. Neurological complications are rare.
 4) Haemophilus influenzae type b (Hib) vaccine
 It contains medium oligosaccharide of H. influenzae type b (10 µg) conjugated with
nontoxic protein (25 µg) of CRM197 mutant Corynebacterium diphtheriae toxin
along with aluminum hydroxide adjuvant.

 It is indicated for protection of infants and children against H. influenzae

meningitis, pneumonia, etc.

 Infants 2–6 months are given 3 doses (0.5 ml i.m.) at 8 week gaps, 7–11 months 2
doses, while those older than 1 yr require only 1 dose.

 Good antibody response and protection has been obtained in > 90% recipients.
 5) Bacillus Calmette-Guérin (BCG) vaccine
 It is a live vaccine bearing an attenuated bovine strain of M. tuberculosis,
developed in 1921 by Calmette and Guérin in France.

 It is supplied as 0.5–1 mg dry powder (1–2.5 × 107 colony forming units) in

ampules to be suspended in 1 ml of sterile water; 0.05 ml (in neonate) 0.1 ml (older
individuals) is injected intracutaneously in the left deltoid region at birth.

 In children and adults tuberculine testing is done beforehand and BCG is given
only to negative responders.

 It is used to enhance resistance to tubercular infection.

 BCG has also been used to enhance immunity nonspecifically by stimulating the
reticuloendothelial system: employed as adjuvant in immunotherapy of cancer and
some other conditions.

 It is contraindicated in tuberculine positive individuals, in those with compromised

host defense including HIV positive children, and during pregnancy
 Viral Vaccines
 Poliomyelitis: The virus (type 1, 2, 3) is grown in monkey kidney cell culture and
two vaccines are prepared from it.

a) Oral poliovirus vaccine (OPV): It is the live virus available in 10 ml and

50 ml vials; each dose is 2 drops, dropped directly in the mouth.

 The virus multiplies in the intestines and produces active immunity, simulating
natural infection, without producing symptoms of the disease.

 For primary immunization, OPV is now generally given at birth and then at 6, 10
and 14 weeks. Booster doses are given between 15–18 months and at school entry.

 OPV is the vaccine of choice for active immunization of children because it is

simple to administer, is well accepted, induces systemic as well as intestinal
immunity, which helps to eliminate carrier state and thus limit the spread of the
disease.

 It is advised to postpone the vaccine in presence of vomiting and diarrhoea.

 b) Inactivated poliomyelitis vaccine (IPV)
 It is inactivated suspension of the virus which is preferred over OPV only for:

 (i) primary immunization in adults (risk of vaccine associated paralysis following

OPV is higher in adults).

 (ii) in persons with compromised immune system. Three doses of 1 ml each are
injected s.c. in the deltoid region at 4–6 week intervals and a fourth is given 6–12
months later.

 Booster doses are given every 5 years.

 Fever and local pain are common. Allergic reactions sometimes occur, probably to
the animal protein present in the vaccine.
 2) Influenza virus vaccine
 Contains inactivated influenza virus A and B.

 Immunization may be done annually or during an epidemic: 2 injections of 0.5–1

ml i.m. 1–2 months apart.

 Influenza virus undergoes frequent antigenic changes; hence the efficacy of the
vaccine is inconsistent.

 It is indicated only in high risk cases.

 Adverse reactions are more common in children: local tenderness and induration
occurs in 30%.

 Fever, malaise and myalgia lasting 1–2 days is less frequent. Allergic reactions to
the egg protein present in the vaccine occur rarely
 3) Hepatitis B vaccine
 The new hepatitis B vaccine is prepared in yeast cells by recombinant DNA
technique and contains aluminium hydroxide adsorbed hepatitis B virus surface
antigen of 20 µg in 1 ml suspension.

 Three 1 ml injections in the deltoid muscle given at 0, 1 and 6 months produce

protective antibody titers in 99% subjects. Children <10 yr are given 0.5 ml doses
in the thigh.

 Now included in universal immunization for all, but is especially indicated in

persons who come in contact with:

 Blood, blood products and other body fluids (surgeons, dentists, blood bank
personnel, laboratory technicians and other health care workers, haemophilics,
haemodialysis patients, drug addicts, etc).

 Induration and soreness at injection site and occasional fever and malaise are the
adverse effects
 Toxoid
1) Tetanus toxoid
 It is formaline treated exotoxin of tetanus bacilli; indicated for routine
immunization in all children and adults.

 Two types of preparations—fluid and adsorbed are available. The adsorbed toxoid is
superior induces higher antibody titers and more prolonged immunity.

 Dose: 0.5 ml, preferable route is i.m., can also be given s.c.

 For primary immunization, tetanus toxoid adsorbed (0.5 ml amp.), 2 doses are given 4-6
weeks apart, or tetanus toxoid fluid (1 ml amp.) 3 doses at interval of 3-4 weeks.
Booster dose should be given after 1 year and then every 10 years.

 In non-immunized or inadequately immunized individuals the toxoid should be given

after any injury. Concomitant administration of chloramphenicol is avoided, as it may
interfere with antibody response.

 Local erythema, pain and induration, axillary lymph nodes may enlarge. Fever, chills,
malaise, aches and pains may occur
 2) Diphtheria toxoid adsorbed

 It is modified diphtheria exotoxin adsorbed onto aluminium hydroxide.

 It is indicated in infants and children below 6 years of age.

 Older individuals seldom require protection against diphtheria.

 For primary immunization 2–3 injections of 0.5 ml i.m. are given 4–6 weeks apart,
booster dose after 1 year and then at school entry.

 Reactions are similar to those caused by tetanus toxoid.

 ANTISERA AND IMMUNE GLOBULINS
 Antisera are purified and concentrated preparations of serum of horses actively
immunized against a specific antigen.

 Immediate type of allergic reactions (urticaria, angioedema, respiratory distress,

anaphylaxis) can occur with any antiserum; adrenaline (1:1000 amp.) should be at
hand while injecting them.

 Prior to each administration, history of serum reactions should be evaluated and an

intracutaneous/scratch test should be performed to check for allergic reactions

 Serum sickness with fever, rash, joint pain, lymphadenopathy appearing 7–12 days
later is more frequent after large doses and repeated administration.

 Local pain, erythema and arthus type reaction without constitutional symptoms
may also occur 7–10 days after i.m. injection.
 Immune globulins (IGs) are separated human gamma globulins which carry the
antibodies.

 These may be nonspecific (normal) or specific (hyperimmune) against a particular

antigen. These are more efficacious than the corresponding antisera.

 Hypersensitivity reactions are very rare with IGs. Skin tests may be misleading and
are not needed.

 However, large doses and repeated injections do increase risk; adrenaline should be
available.

 Transient local tenderness and stiffness of injected muscle is occasional. Serum

sickness does not occur with human IGs
Classification of Antisera and Immune Globulins
Thank you for your attention
Remain safe!!