BIOLOGICS

BIOLOGICS
• Any virus, therapeutic serum, toxin, antitoxin or analogous
product.
• Such products includes vaccines of bacterial, rickettsial
and viral origin, immune serums for the prevention or
treatment of disease, various miscellaneous and
diagnostic products, human blood and products derived
from human blood.
• SOURCE:
• ANIMALS- serums, antitoxins,globulins
• MICROSCOPIC PLANT ORGANISMS - vaccines,
toxins, toxoids,tuberculins
Antigens
• The material that provokes the immune response
• Biologic: When introduced into the tissue of humans or other vertebrates it
causes the formation of antibodies, therefore reacting with the antigen
• Immunogenicity: induce antibody formation
• Specificity: antigenic determinants (sites)
• Considered foreign by the antibody-forming host

• Chemical: protein
• Physical: high MW (>10,000 daltons)
• Examples: exotoxins, proteins and polysaccharides on the cell surface and
capsules of bacteria, and the protein coat of virus particles
• Epitope: simplest form of antigenic determinant
• Haptens: antigens <10,000 daltons MW; lack immunogenicity
ANTIBODIES
• found predominantly in the serum fraction of the
blood, body fluids, in other tissues such as lymph nodes
and mucous membranes
• 4 fractions
• Serum albumin
• Alpha globulins
• Beta globulins
• Gamma globulins
• Immunoglobulins: antibodies that occur in gamma
globulin fraction
 IMMUNOGLOBULINS
IgG 150,000 Da Most abundant; 80% of the
1,400 amino acids serum antibody found after
bacterial and viral infections
IgM First immunoglobulin to Major Ig expressed on
appear; efficient in the surface of B cells
agglutinating erythrocytes or
bacteria; ABO antibodies are of
this type
IgA Chain A: 70,000 Da Predominant Ig in secretions;
Chain B: 15,000 Da defense mechanism
IgD Main function not determined;
found on the surface of B
Found in low
lymphocytes; maybe involved
concentrations in the
in cell differentiation; role is an
blood serum
antigen receptor
IgE Reagins; constitute 0.004% of
the total serum Ig; binds to
mast cells releasing histamine
TYPES OF IMMUNITY
• Natural (Innate) immunity – endowed at birth and retained
because of an individuals constitution
• Acquired immunity
• Active immunity: developed in response to the introduction of
antigenic substances into the body
• Naturally acquired active: recovery from infections
• Artificially acquired active: administration of a vaccine or toxoid; stimulating
the body to make their own antibodies therefore producing immunity
• Passive immunity: developed by the introduction of preformed
antibodies (not antigens) into the body; immunity is not self-developed
but is passed from one individual to another
• Naturally acquired passive: transmission of antibodies from mother to child
• Artificially acquired passive: injection of immunizing biologics containing
preformed antibodies
 B cell
Origin of serum antibodies
Arise from the bone marrow of
humans
Humoral system of immunity
Circulate in the body fluids (blood)
Handles most of the infectious
organisms
T cell
Originate in the BM but depend on
the thymus gland for
differentiation
Agents of cellular immunity
Seldom found circulating in the
blood
Responsible for delayed
hypersensitivity
Serve as the sentinels of immune
surveillance against cancer and
mediators of graft rejection
• B cells
• B memory cells: serve as the immune system’s memory, providing
faster response to any exposure to the same antigen
• Plasma cells: grow larger, stop reproduction and continuously
secrete large quantities of antibody

T cells
TC cells Cytotoxic, attack cell
membranes bearing their
specific antigen
Cell mediated immunity
TD cells Delayed hypersensitivity cells
(lymphokines)

TH cells Helper cells; stimulate B cells

and other T cells specific for
that antigen (proliferation and
differentiation) Immunoregulatory role

TS cells Suppressor cells; opposite

effect of helper cells
Biologics
• All biologics have an expiration date
• Diphtheria antitoxin: 5-year exp date provided the
preparation has a 20% excess of potency
• Refrigerated: 2-8°C
• Yellow fever vaccine: 0-5 °C
• Live poliomyelitis vaccine: below -10 °C
Vaccines
• Train the immune system to create antibodies
• Contain killed or weakened forms of viruses or
bacteria
• Recognizes the invading virus or bacteria
• If an individual gets exposed to the germ in the
future, the immune system can quickly destroy it
 VACCINES
• may contain living, attenuated, or killed viruses, killed rickettsiae or
attenuated or killed bacteria and they are used as inoculations to
stimulate the production of antibodies
• Active immunization with living agents is generally preferable to
immunization with killed vaccines because of a superior and more
long-lived immune response (ex: measles, rubella, mumps vaccine)
• Nonliving vaccines: provide protection for a short period of time and
repeated vaccination is required to maintain protection (ex: typhoid
fever, cholera, plague, typhus)
Vaccines
• The benefits of active immunization far outweigh the
dangers associated with the use of vaccines; however,
precautionary measures should be followed to ensure
optimum effectiveness with a minimum of adverse
reactions
• Use of vaccines is contraindicated under conditions in
which the immune response may be depressed, such as
during therapy involving corticosteroids, antineoplastic
agents, immunosuppressive agents, or radiation; in
patients with immunoglobulin deficiency and in
patients with latent or active infections
Vaccines
• May cause fever, malaise and soreness at injection
sites
• Rubella vaccine: arthralgia, arthritis
• Pertussis vaccine: convulsions
• 1976: swine flu vaccine; individuals developed
Guillain-Barre syndrome (acute febrile
polyneuritis); resulted in 5% mortality rate
• Allergic reactions may result
Viral vaccines
• Prophylaxis against mumps, rubella, rubeola,
smallpox, yellow fever (live viruses)
• Inactivated or killed viruses are used in influenza
and rabies vaccines
• Live attenuated or killed viruses for poliomyelitis
Smallpox vaccine
• Living virus of cowpox that has been grown
in the skin of a vaccinated bovine calf
• 0.5% phenol as a preservative
• Dr. Edward Jenner
• Liquid vaccine: kept below 0°C
• Dried vaccine: 2-8 °C
• Immunizing agent and prophylactic before
infection occurs
• Active immunity lasts for 7 years
Rabies vaccine
• Human diploid cell rabies vaccine (HDCV)
• Sterile lyophilized preparation of either the whole
virion or subvirion rabies virus
• whole virion vaccine is prepared from Wistar rabies virus
grown in cultures of human diploid embryo lung tissue and
inactivated with tri-N-butyl phosphate and β-
propiolactone
• subvirion vaccine is prepared from the Pasteur-derived
Pitman-Moore virus grown on human diploid cell cultures
developed in Europe and inactivated with β-propiolactone
• Series of injections for 28 days, development of
antibodies inhibits the growth of the virus
• Active immunizing agent in the prevention of rabies in
persons bitten by rabid animals
Yellow fever vaccine
• Attenuated strain of living yellow fever
virus
• Prepared by culturing the virus in the
living embryo of the domestic fowl
(Gallus domesticus)
• Exp date is not longer than 1 year
• Storage temp is below 0°C but never
above 5 °C
• Aedes mosquito is the vector of yellow
fever or yellow jack
• Active immunizing agent used to
develop active immunity against the
disease
Influenza virus vaccine
• sterile aqueous suspension of suitably
inactivated influenza virus types A and B
(bivalent vaccine) either individually or
combined or virus subunits prepared
from the extra-embryonic fluid of
influenza virus-infected chick embryo
• Contains a preservative and adsorbent,
aluminum phosphate or protamine
• the virus growths are collected,
concentrated, refined by
ultracentrifugation, and inactivated by
UV irradiation
• Stored between 2-8°C
• Active immunizing agent; IM (deltoid
muscle)
Poliomyelitis vaccine
• Polio vaccine inactivated (IPV); Salk polio vaccine
• sterile suspension of inactivated poliomyelitis virus of types 1, 2, and 3 (trivalent
vaccine)
• virus strains are grown separately in primary cultures of Rhesus monkey kidney
tissues; formaldehyde is used to kill the viruses
• 1908: Landsteiner and Popper first transmitted and isolated poliomyelitis virus
experimentally in monkeys
• 1948: Dr. John Enders originated a method of cultivating polio virus in vitro on
animal tissues other than nervous tissue; awarded the Nobel Peace prize
• 1953: Dr. Jonas Salk perfected the roller-coaster method of polio virus culture
and the final detoxified form of polio vaccine
Poliovirus vaccine
live oral
• trivalent oral polio vaccine (TOPV)
• preparation of one or a combination of the 3 types of live, attenuated
polioviruses
• The manufacture of poliovirus vaccine live oral is similar to that of poliovirus
vaccine inactivated (Salk), However, the viruses are not killed by treatment with
formaldehyde, as is done with Salk vaccine; instead, the viruses are attenuated.
• manufactured and tested in a manner suited only for oral administration and is
free from any known microbial agent other than the attenuated poliovirus or
polioviruses intended to be present
• Dr. Albert Sabin of the University of Cincinnati, Dr. Harold Cox of Lederle
Laboratories and Dr. Hilary Koprowski of the Wistar Institute of Philadelphia
Poliovirus vaccine live oral
• The attenuated live virus, when present in the
intestinal tract, multiplies and produces a localized
resistance to reinfection by the same type of virus,
thus stimulating the production of typespecific
serum antibodies
• Generally frozen, stored at -10°C
Measles vaccine
• Vaccines containing live attenuated rubeola
(measles) and rubella (German measles) viruses are
available for active immunization
• grown on cultures of either avian embryo tissue or
human diploid cell tissue
• stored at a temperature of between 2 and 8°C and
have a 1-year expiration date.
Measles virus vaccine live or
rubeola vaccine
• prepared from attenuated viruses derived from the
original Edmonston B strain
• grown on cultures of chicken embryo tissue.
Rubella virus vaccine live
• prepared from the Wistar Institute RA 27/3 strain grown on
human diploid cell tissue
• recommended for active immunization against German
measles
• should not be administered to pregnant or immediate
postpartum women, and special caution must be exercised
if it is given to sexually active females
Mumps virus vaccine live
• prepared with the B-level Jeryl Lynn strain of the
virus, which is grown in cell cultures of chicken
embryo tissue
• It provides active immunity for at least 10 years
after immunization and is particularly valuable to
susceptible individuals approaching puberty and to
adults
• Not recommended for infants less than 1 year old
because they may retain maternal mumps
antibodies that may interfere with the immune
response
Hepatitis B vaccine
• composed of chemically inactivated hepatitis B
surface antigen (HBsAg) particles obtained from the
plasma of healthy chronic HBsAg carriers by
plasmapheresis, separated from the infectious
Dane particle by density gradient centrifugation,
and absorbed on aluminum hydroxide
Rickettsial vaccines
• Rickettsiae are cultured in chick embryos or in
monkey kidney tissue cultures in a manner similar
to that for viruses
• No vaccine is available for preventing rickettsial
infections (CDC)
Bacterial vaccines
• consist of suspensions of attenuated or, more
commonly, killed pathogenic bacteria in isotonic
sodium chloride solution or other suitable diluents.
• Suspensions of young, living organisms grown in
standard culture media are killed chemically, by
application of moist heat at a temperature slightly
above the thermal deathpoint, or by exposure to
ultraviolet light
Typhoid Vaccine
• sterile suspension or solid containing killed typhoid
bacilli (Salmonella typhi)
• Enteric vaccine: because it prevents the effect of
the disease on the intestinal tract.
Cholera Vaccine
• sterile suspension of killed cholera virus (Vibrio
cholerae) in isotonic sodium chloride solution or
other suitable diluent
• prepared from equal portions of suspensions of
cholera vibrios of the Inaba and Ogawa strains
• Inaba Strain possesses an antigenic value not less than
that of N.I.H. Inaba strain 35-A-3, and the Ogawa strain
possesses an antigenic value not less than that of N.I.H.
Ogawa strain 41
• stored at a temperature between 2 and 8°C, and
the expiration date is not longer than 18 months
from the date of issue
Plague Vaccine
• sterile suspension, in an isotonic sodium chloride solution or
other suitable diluent, of killed plague bacilli (Yersinia pestis)
• bacteria causing bubonic and pneumonic plague in humans are named
Yersinia in honor of the Swiss bacteriologist Yersin, who was the first to
isolate and identify the disease-causing organism
• Rats serve as an animal reservoir for the organisms, but the disease is
transmitted to humans through the bites of fleas that infest the rats
• Its use is generally restricted to travelers to known plague areas,
including Mongolia, southwestern Russia, central China, India,
Pakistan, Nepal, Indonesia, Vietnam, South Africa, Saudi Arabia,
Brazil, Bolivia, and Peru
Pertussis Vaccine
• sterile bacterial fraction or suspension of killed
pertussis bacilli (Bordetella pertussis)
• stored at a temperature between 2 and 8°C and
must be protected against freezing; expiration date
is not later than 18 months from the date of issue
• Bordetella pertussis is the organism that causes the
disease known as whooping cough or pertussis
BCG Vaccine
• dried, living culture of the bacillus Calmette-Guérin
strain of Mycobacterium tuberculosis var. bovis
• expiration date of BCG vaccine is up to 1 year if it is
stored at 5°C
• active immunizing agent against tuberculosis
Meningococcal polysaccharide
vaccines
• contain the specific bacterial capsular
polysaccharides for Neisseria meningitidis
Serogroups A, C, Y, and W-135
• The use of meningococcal polysaccharide vaccine is
indicated for children over 2 years of age and for
military recruits and adult populations at risk in
epidemic areas.
Pneumococcal vaccine polyvalent
• protection against the
23 most prevalent
capsular types of
pneumococci
• prepared by isolating
and purifying the
polysaccharide antigens
from strains of
Streptococcus
pneumoniae
Haemophilus b polysaccharide
vaccine
• composed of the
purified, capsular
polysaccharide of
Haemophilus influenzae
type b (Hib)
• Hib can cause epiglottitis,
osteomyelitis, arthritis,
cellulitis, and pneumonia
in children
 Diagnostic agents

Source Diagnostic aid

Tuberculins Tubercle bacillus tuberculosis Marked redness
Old Tuberculin Tubercle bacillus tuberculosis Palpable induration
5mm in diameter
Histoplasmin Histoplasma histoplasmosis
capsulatum
Coccidioidin Coccidioides immitis coccidioidomycosis
Diphtheria toxin Corynebacterium diphtheria 1cm or more in
diphtheriae diameter
Mumps skin test Mumps virus Mumps 1.5cm in diameter
antigen
tuberculin P.P.D. Tubercle bacillus tuberculosis Palpable induration
10mm or more
Toxins and Toxoids
• Toxins are bacterial waste products that are
considered poisonous to the animal body
• they act as antigens because of their power to stimulate
certain cells of the body to produce antibodies called
antitoxins
• Exotoxins: toxins are excreted from the bacterial
cells producing them and are dissolved in the
surrounding culture medium
• Endotoxins: retained within the bacterial body
Clostridium botulinum
• source of the most poisonous poison
• Compared to other toxins, botulinum toxin has a
potency range 10-1000 times higher
• Ingestion of exotoxin can cause death
 Treated with
fluid toxoids formaldehyde
precipitating or
adsorbing the fluid Used to produce
toxoid with alum, active immunity
aluminum hydroxide, against diphtheria
or aluminum and tetanus
phosphate; more
Adsorbed toxoid prone to produce DTP: triple antigen;
local reactions at the diphtheria, tetanus,
site of injection than pertussis
are fluid toxoids
Antitoxins
• prepared from the blood of animals, usually horses, that have been
immunized by repeated injections of specific bacterial exotoxins
• Prepared in 2 methods
• Precipitation using ammonium sulfate; pseudoglobulin fraction is redissolved,
dialyzed and filtered
• Pepsin solution to digest the plasma removing 80% of the protein; digested
material is treated with ammonium sulfate, redissolved, dialyzed and filtered
• Sensitivity testing should be done before administration
• intracutaneous inj 0.02ml of 1 1:100 dilution
• Eye drop on one eye 1:100 dilution into the conjunctival sac
• Measures to counter an anaphylactic shock
• Epinephrine inj and a tourniquet
Diphtheria potency of not less than 500
antitoxin antitoxin units per ml.
Tetanus antitoxin potency of not less than 400
antitoxin units per ml.
Botulism Antitoxin multivalent antitoxin is used to treat sterile, nonpyrogenic
all cases of toxemia caused by the
types of botulinus bacteria
Passive immunizing agents;
used for prophylaxis and
treatment of the specific
disease
solution of the refined and
concentrated antitoxic
antibodies, chiefly
globulins, obtained from
the blood serum or plasma
of healthy horses that have
been immunized against
the toxins
stored at a temperature of
between 2 and 8° C
VENOMS AND ANTIVENINS
• Venoms are poisonous excretions produced by
animals; they can be compared with the toxic
waste products (exotoxins) of bacteria
• Snake venins or venoms are obtained by holding a
poisonous snake over a conical glass container
covered with a sheet of thin rubber
Antivenin (Crotalidae)
Polyvalent
Antivenin (Micrurus fulvius)
Antivenin (Latrodectus
mactans)
North and South American
antisnakebite serum
North American coral snake
antivenin
black widow spider antivenin
4 species of pit vipers
• Crotalus atrox (Western
diamondback)
• C. adamanteus (Florida
diamondback)
• C. durissus terrificus (South
American rattlesnake)
• Bothrops atrox (South
American fer-de-lance)
(Crotalidae)
venom of Micrurus fulvius, the
eastern coral snake; also
neutralizes M. fulvius tenere
(Texas coral snake) but not
Micruroides euryxanthus
(Arizona or Sonoran coral
snake)
venom of the black widow
spider (Latrodectus nwctans
 ANTISERUMS
• biologics prepared in a manner similar to
that for antitoxins and antivenins except
that bacteria or viruses are used to
stimulate the production of specific
antibodies in a healthy animal such as the
horse
• The therapeutic effectiveness of
antiserums is based on their production
of artificial passive immunity
• each antiserum is a specific biologic
employed to provide a supply of ready-made
antibodies to combat the disease
IMMUNE GLOBULINS
• immunizing biologics that contain specific antibodies
derived from the blood of humans who have survived an
attack of a specific disease or who have been immunized in
some other manner
• Chances of sensitization are less with human serum
derivatives than with immune serums from animal sources
• Obtained from the plasma or serum pool of a large number
or random donors or from a limited number of individuals
who have been hyperimmunized against a specific antigenic
material
• stored at a temperature of between 2 and 8°C
• expiration date is usually not more than 3 years after the
date of issue
• Offer artificial passive immunity
Immune Globulin
Gamma globulin
Immune globulin intravenous
(IGIV)
Pertussis immune globulin
Tetanus immune globulin
prophylactic value in chicken
pox, hepatitis A, rubella, and
other diseases
provides immediate antibody
levels
derived from the blood prophylaxis and treatment of
plasma of adult human donors pertussis
who have previously been
immunized with pertussis
vaccine
derived from the blood
plasma of adult human donors
who have been immunized
with tetanus toxoid
given to treat gamma globulin
deficiency for the prevention
of recurrent infections
used in the treatment of
immunodeficiency syndrome,
especially in patients who
require an immediate increase
in immunoglobulin blood
levels
useful for passive
immunization against tetanus
in individuals with wounds
that may have been
contaminated with tetanus
microorganism
Rabies Immune Globulin from plasma of donors indicated for passive
hyperimmunized with rabies vaccine protection against rabies in
persons suspected of
exposure to rabies

Its use is the same as

antirabies serum; however,
because it is of human origin,
it possesses the added
advantage of removing the
risk of serum sickness

Hepatitis B immune prepared from pooled plasma Hepatitis B

globulin obtained from donors with high
titers of antibody to hepatitis B
surface (HBs) antigen

Varicella-zoster immune globulin fraction of human plasma, Chicken pox

globulin primarily immunoglobulin G, found
in routine screening of normal
volunteer blood donors
RH0 (D) Immune derived from human blood
Globulin plasma containing antibody to
the erythrocyte factor Rh0 (D)
Lymphocyte Immune a lymphocyte selective
Globulin immunosuppressant that is
prepared by immunizing horses
with human thymus cells and
then isolating the equine
gamma globulin
RHD factor: antibody that
neutralizes the antigen in
Rh-positive blood, which
sensitizes Rh-negative
women and results in Rh
hemolytic disease of the
newborn
indicated for use in organ
transplant.
Whole blood
Used as a blood replenisher
Red blood cells
used as a blood replenisher;
anemia
Thrombin
• local hemostatic
• applied topically to control
blood oozing from
capillaries and small
venules when the area is
accessible
• useful in dental surgery,
laryngeal and nasal surgery,
plastic surgery, and skin
grafting procedures
blood that has been drawn stored at a constant
from a selected donor under temperature of between 1 and
rigid aseptic conditions, 6° C
contains citrate ion or heparin
as an anticoagulant Note exp date in the book
depending on the
anticoagulant used
whole blood from which storage at —65° C or colder
plasma has been removed
prepared from prothrombin of Solutions should be used
bovine origin through within a few hours after
interaction with added preparation
thromboplastin in the
presence of calcium
Antihemophilic Derivatives
• Antihemophilic factor: sterile, freeze-dried concentrate of human
antihemophilic factor (prepared from the factor VIII-rich cryoprotein
fraction of human venous plasma) for use in the therapy of hemophilia
A (classic hemophilia) by accelerating the abnormally slow clotting time.
• Factor VIII is needed for the transformation of prothrombin to thrombin by the
intrinsic pathway
• Antihemophilic factor IX complex: dried plasma fraction comprising
coagulation factors IX (plasma thromboplastin component), II
(prothrombjn), VII (proconvertin), and X (Stuart-Prower factor)
• indicated to prevent a dangerous bleeding episode or to perform surgery
whenever one or more of these specific coagulation factors is absent in the
blood of a patient
Albumin Human
• obtained by fractionating material (source blood,
plasma, serum, or placentas) from healthy, human
donors
• tested for the absence of hepatitis B surface
antigen
• blood-volume supporter
Plasma Protein Fraction

• derived by fractionating material (source blood,

plasma, or serum) from healthy human donors and
testing for the absence of hepatitis B surface
antigen
• indicated for restoration of blood volume when the
patient is in a state of shock caused by burns,
crushing injuries, and any other causes, in which
loss of plasma fluids., not loss of red blood cells, is
predominant
• blood-volume supporter
Radio-Iodinated Serum Albumins
• Human serum albumin iodinated 125I or 131I
• Iodination is controlled to introduce not more than
1 gram-atom of iodine for each gram-molecule
(60,000 g) of albumin
• sterile, buffered, isotonic solutions prepared to
contain not less than 10 mg of radio-iodinated
normal human albumin per ml and adjusted to
provide not more than 1 millicurie of radioactivity
per ml
Iodinated 125I albumin diagnostic aids for
injection and iodinated 131I determining blood volume
albumin injection and cardiac output

iodinated 131I aggregated diagnostic aid for

injection determination of pulmonary
clearance