Biologics Biologics

BiologicsBiologicsWide range of medicinal products produced by biological processes .

Isolated from a variety of natural sources and may be produced by biotechnology methods and other technologies

Composed of sugars, proteins, or nucleic acids or complex combinations of these substances, or may be living entities such as cells and tissues.

Biologics – also known as “biologicals”

They include:They include:

vaccinesvaccines

blood and blood derivativesblood and blood derivatives

allergenic patch tests and extractsallergenic patch tests and extracts

tests to detect HIV and hepatitistests to detect HIV and hepatitis

gene therapy productsgene therapy products

cells and tissues for transplantation, cells and tissues for transplantation,

new treatments for cancers, arthritis, and other serious new treatments for cancers, arthritis, and other serious diseases. diseases.

VaccineVaccine

Active immunization Active immunization because the immune system is stimulated to develop its own immunity against the pathogen.

Passive immunity Passive immunity from the injection of antibodies formed by another animal (e.g., horse, human) which provide immediate protection for the recipient. .

Figure 17.5 The characteristics of immunity produced by active immunization and passive immunotherapy

Passiveimmunotherapy

Injection

BoostersActiveimmunization

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Principles of VaccinationPrinciples of Vaccination

A live or inactivated substance A live or inactivated substance (e.g., protein, polysaccharide) (e.g., protein, polysaccharide) capable of producing an immune capable of producing an immune responseresponse

Protein molecules (immuno-Protein molecules (immuno-globulin) produced by B globulin) produced by B lymphocytes to help eliminate an lymphocytes to help eliminate an antigen antigen

AntigenAntigen

AntibodyAntibody

A vaccine :

is a biological preparation that improves immunity to a particular disease.

typically contains an agent that resembles a disease-causing microorganism.

The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters.

 

Classification of VaccinesClassification of VaccinesInactivatedInactivated

Live attenuatedLive attenuated

viralviral

bacterialbacterial

KilledKilled

Vaccines containing killed microorganisms – these are Vaccines containing killed microorganisms – these are previously virulent micro-organisms which have been killed previously virulent micro-organisms which have been killed with chemicals or heat. Examples are vaccines against flu, with chemicals or heat. Examples are vaccines against flu, cholera, bubonic plague, polio and hepatitis A.cholera, bubonic plague, polio and hepatitis A.

AttenuatedAttenuated

Some vaccines contain live, attenuated microorganisms. Some vaccines contain live, attenuated microorganisms.

The organism has been cultured so as to reduce its The organism has been cultured so as to reduce its pathogenicity, but still retain some of the antigens of the pathogenicity, but still retain some of the antigens of the virulent form. virulent form.

They typically provoke more durable immunological They typically provoke more durable immunological responses and are the preferred type for healthy adults. responses and are the preferred type for healthy adults.

Examples include the viral diseases yellow fever, measles, Examples include the viral diseases yellow fever, measles, rubella, and mumps and the bacterial disease typhoid. The rubella, and mumps and the bacterial disease typhoid. The live Mycobacterium tuberculosis vaccine developed by live Mycobacterium tuberculosis vaccine developed by Calmette and Guérin is not made of a contagious strain, Calmette and Guérin is not made of a contagious strain, but contains a virulently modified strain called "BCG" used but contains a virulently modified strain called "BCG" used to elicit immunogenicity to the vaccine.to elicit immunogenicity to the vaccine.

Live Attenuated VaccinesLive Attenuated Vaccines

Attenuated form of the "wild" virus Attenuated form of the "wild" virus or bacteriumor bacterium

Must replicate to be effectiveMust replicate to be effective

Immune response similar to natural Immune response similar to natural infectioninfection

Usually effective with one doseUsually effective with one dose

Live Attenuated VaccinesLive Attenuated Vaccines

Severe reactions possibleSevere reactions possible

Interference from circulating Interference from circulating antibodyantibody

Fragile – must be stored and Fragile – must be stored and handled carefullyhandled carefully

Inactivated VaccinesInactivated Vaccines

Cannot replicateCannot replicate

Generally not as effective as live Generally not as effective as live vaccinesvaccines

Less interference from circulating Less interference from circulating antibody than live vaccinesantibody than live vaccines

Generally require 3-5 dosesGenerally require 3-5 doses

Antibody titer may diminish with timeAntibody titer may diminish with time

Inactivated VaccinesInactivated Vaccines

virusesvirusesbacteriabacteria

protein-basedprotein-based

toxoid toxoid subunitsubunit

polysaccharide-basedpolysaccharide-based

purepure conjugateconjugate

Whole

Fractional

Toxoid Toxoid

In some diseases, In some diseases, diphtheriadiphtheria and and tetanustetanus are are notorious examples, it is not the growth of the notorious examples, it is not the growth of the bacterium that is dangerous, but the protein toxin bacterium that is dangerous, but the protein toxin that is liberated by it.that is liberated by it.

Treating the toxin with, for example, Treating the toxin with, for example, formaldehyde, denatures the protein so that it is formaldehyde, denatures the protein so that it is no longer dangerous, but retains some epitopes no longer dangerous, but retains some epitopes on the molecule that will elicit protective on the molecule that will elicit protective antibodies. antibodies.

SubunitSubunit

Protein subunit – rather than introducing an inactivated or Protein subunit – rather than introducing an inactivated or attenuated micro-organism to an immune system (which attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine)would constitute a "whole-agent" vaccine)

A fragment of it can create an immune response. A fragment of it can create an immune response.

Examples include :Examples include :

the subunit vaccine against Hepatitis B virus that is the subunit vaccine against Hepatitis B virus that is composed of only the surface proteins of the virus composed of only the surface proteins of the virus (previously extracted from the blood serum of chronically (previously extracted from the blood serum of chronically infected patients, but now produced by recombination of infected patients, but now produced by recombination of the viral genes into yeast), the viral genes into yeast),

the virus-like particle (VLP) vaccine against human the virus-like particle (VLP) vaccine against human papillomavirus (HPV) that is composed of the viral major papillomavirus (HPV) that is composed of the viral major capsid protein, capsid protein,

and the hemagglutinin and neuraminidase subunits of the and the hemagglutinin and neuraminidase subunits of the influenza virus.influenza virus.

ConjugateConjugate

certain bacteria have polysaccharide outer certain bacteria have polysaccharide outer coats that are poorly immunogenic. By coats that are poorly immunogenic. By linking these outer coats to proteins (e.g. linking these outer coats to proteins (e.g. toxins), the immune system can be led to toxins), the immune system can be led to recognize the polysaccharide as if it were a recognize the polysaccharide as if it were a protein antigen. This approach is used in protein antigen. This approach is used in the Haemophilus influenzae type B vaccine.the Haemophilus influenzae type B vaccine.

Immunisation Department, Centre for Infections

Carrierprotein

Polysaccharide linked to carrier protein

Conjugate vaccineBacteria

Polysaccharide (sugar) coating

Conjugation

Conjugation is the process of attaching (linking) the polysaccharide antigen to a protein carrier (e.g. diphtheria or tetanus) that the infant’s immune system already recognises in order to provoke an immune response

ValenceValence

Vaccines may be monovalent (also called Vaccines may be monovalent (also called univalent) designed to immunize against a single univalent) designed to immunize against a single antigen or single microorganismantigen or single microorganism

or multivalent (also called polyvalent). designed or multivalent (also called polyvalent). designed to immunize against two or more strains of the to immunize against two or more strains of the same microorganism, or against two or more same microorganism, or against two or more microorganisms. microorganisms.

In certain cases a monovalent vaccine may be In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune preferable for rapidly developing a strong immune response.response.

Immunisation Department, Centre for Infections

Vaccine compositionIn addition to the antigen, vaccines may contain some or all of the following components:

ComponentPurposeExample

Adjuvantsenhance the immune response to a vaccine

aluminium salts

Preservativesprevent bacterial or fungal contamination of vaccine

thiomersal

Additivesstabilise vaccines from adverse conditions such as freeze-drying or heat, thereby maintaining a vaccine’s potency

gelatine

Residuals from manufacturing process

Inactivating agents

Antibiotics - prevent bacterial contamination during manufacturing process

Egg proteins- some vaccine viruses are grown in chick embryo cells

Yeast proteins

formaldehyde

neomycin, streptomycin, polymyxin B

influenza, yellow fever

HepB vaccine

Developing immunityDeveloping immunityThe immune system recognizes vaccine agents as The immune system recognizes vaccine agents as foreign, destroys them, and 'remembers' them. foreign, destroys them, and 'remembers' them.

When the virulent version of an agent comes along When the virulent version of an agent comes along the body recognizes the protein coat on the virus, the body recognizes the protein coat on the virus, and thus is prepared to respond, by and thus is prepared to respond, by

(1) neutralizing the target agent before it can enter (1) neutralizing the target agent before it can enter cells, and cells, and

(2) by recognizing and destroying infected cells (2) by recognizing and destroying infected cells before that agent can multiply to vast numbers.before that agent can multiply to vast numbers.

When two or more vaccines are mixed together in When two or more vaccines are mixed together in the same formulation, the two vaccines can the same formulation, the two vaccines can interfere. interfere.

This most frequently occurs with live attenuated This most frequently occurs with live attenuated vaccines, where one of the vaccine components is vaccines, where one of the vaccine components is more robust than the others and suppresses the more robust than the others and suppresses the growth and immune response to the other growth and immune response to the other components. components.

EffectivenessEffectivenessVaccines do not guarantee complete protection from Vaccines do not guarantee complete protection from a disease.a disease.

Sometimes this is because the host's immune Sometimes this is because the host's immune system simply doesn't respond adequately or at all. system simply doesn't respond adequately or at all. This may be due to a lowered immunity in general This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection) or because the (diabetes, steroid use, HIV infection) or because the host's immune system does not have a B cell host's immune system does not have a B cell capable of generating antibodies to that antigen.capable of generating antibodies to that antigen.

Even if the host develops antibodies, the human Even if the host develops antibodies, the human immune system is not perfect and in any case the immune system is not perfect and in any case the immune system might still not be able to defeat the immune system might still not be able to defeat the infection.infection.

Adjuvants are typically used to boost immune response. Most often aluminium adjuvants are used Squalene are also used in some vaccines .

The efficacy or performance of the The efficacy or performance of the vaccine is dependent on a number of vaccine is dependent on a number of

factors:factors:the disease itself (for some diseases vaccination the disease itself (for some diseases vaccination performs better than for other diseases) .performs better than for other diseases) .

the strain of vaccine (some vaccinations are for the strain of vaccine (some vaccinations are for different strains of the disease) .different strains of the disease) .

whether one kept to the timetable for the whether one kept to the timetable for the vaccinations .vaccinations .

some individuals are 'non-responders' to certain some individuals are 'non-responders' to certain vaccines, meaning that they do not generate vaccines, meaning that they do not generate antibodies even after being vaccinated correctly. antibodies even after being vaccinated correctly.

other factors such as ethnicity or genetic other factors such as ethnicity or genetic predisposition .predisposition .

Compulsory VaccinesCompulsory Vaccines

Bacillus Calmette‑Guerin Vaccine (BCG)

INDICATIONS All newborns All tuberculin negative infants

  PRECAUTIONS & CONTRAINDICATIONS(CI):

Give only to PPD negative children CI in persons with immunodeficiencies CI during pregnancy 

Bacillus Calmette‑Guerin Vaccine (BCG)

SIDE EFFECTS Local

Skin ulceration, regional lymphadenitis Subcutaneous abscess

Generalized

Anaphylaxis, generalized BCG infection (rare): osteitis

Hepatitis B

PREPARATIONS ENGERIX‑B RECOMBIVAX HB

Hepatitis B

ADMINISTRATION: 0.5 ‑1 ML, anterolateral thigh or deltoid IM injection at 0,1 and 6 months 

SIDE EFFECTS: Pain Arthralgia

Poliomyelitis Prophylaxis

PREPARATIONS (A) Oral (OPV) SABIN (Live attenuated) (B) Inactivated (eIPV) SALK (killed)

ADMINISTRATION OPV 2 drops orally eIPV SC injection

PRECAUTIONS & CONTRAINDICATIONS(CI)  (a) OPV pregnancy, immunodeficiency (b) IPV neomycin hypersensitivity

ADVERSE REACTIONS OPV paralytic disease (rare)

Diphtheria, Tetanus & Pertussis (DTP)

PREPARATIONS < 7 years : DTP, DT, DTaP (acellular

pertussis vaccine) > 7 years : Td, TdaP

ADMINISTRATION IM

Diphtheria, Tetanus & Pertussis (DTP)

CONTRAINDICATIONS (CI) Encephalopathy within 7 days Progressive or unstable neurological disorders Anaphylactic reaction to a previous dose

PRECAUTIONS severe systemic reactions such as

Temp > 40.50C persistent inconsolable crying > 3 hours Collapse episodes Convulsions

Measles, Mumps & Rubella (MMR)

PREPARATIONS: MEASLES. MMR.

ADMINISTRATION: SC.

 INDICATIONS: Primary immunization at 1 & 6 years.

Measles, Mumps & Rubella (MMR)

PRECAUTIONS & CONTRAINDICATIONS Pregnancy Anaphylaxis to eggs Immunodeficiency and

immunosuppression Immunoglobulins within 3-11 months

Measles, Mumps & Rubella (MMR)

ADVERSE REACTIONS Fever ,rash (7 days post vaccination) Arthralgia , arthritis (rubella) Encephalitis [rare] (measles, mumps) Suppression of PPD skin test (measles) Convulsions in prone children(measles) Thrombocytopenia

Haemophilus Influenzae Type B

ADMINISTRATION IM 2,4,6 months, booster at 15 months

INDICATIONS Children under 5 years of age High risk children

SIDE EFFECTS: Local pain and erythema Mild fever

Varicella Prophylaxis

PREPARATIONS: Varivax vaccine (MSD)

ADMINISTRATION: 0.5 ml IM 12 months and above……..2 doses 

 

Varicella Prophylaxis

INDICATIONS: All children 12 months‑18 years: (if no

history of varicella) EFFICACY:

70‑90% 

Varicella Prophylaxis

PRECAUTIONS & CONTRAITNDICATIONS: Immunocompromised patients Within 5 months of IG Children on long term salicylates 

SIDE EFFECTS: Fever , rash Zoster

Hepatitis A

NATURE OF VACCINE: Killed formalin inactivated vaccine.

PREPARATIONS: Various preparations available

e.g. Havrix 720 Junior, Havrix 1440 etc.

Hepatitis A

INDICATIONS: children 1 year and above

Susceptible children in endemic areasChronic liver diseaseHemophilia

Hepatitis A

ADMINISTRATION: IM injection 2 doses, at least 6 months apart

ADVERSE REACTIONS: Local reactions, fever Rare: anaphylaxis

Additional VaccinesAdditional Vaccines

Pneumococcal Prophylaxis

PREPARATIONS: Purified capsular polysaccharide of 23

serotypes of Streptococcus pneumoniae 7 valent conjugated vaccine

ADMINISTRATION: IM / SC 1 dose/booster 5 years

Pneumococcal Prophylaxis

INDICATIONS: Primary vaccination (conjugate vaccine) children 2 yr. or older with

Anatomical or functional asplenia Sickle cell disease Nephrotic syndrome Immunosuppression

Pneumococcal Prophylaxis

SIDE EFFECTS:Soreness , erythema, fever, myalgiaAnaphylactic reactions (rare)

Meningococcal Prophylaxis

PREPARATIONS: monovalent (A or C) bivalent (A & C) quadrivalent (A,C,Y & W‑135) quadrivalent conjugate quadrivalent

ADMINISTRATION: SC

Meningococcal Prophylaxis

INDICATIONS: Control of outbreaks Children with complement deficiencies

or asplenia SIDE EFFECTS:

local erythema and discomfort transient fever

Influenza Virus

Nature of vaccine: Killed vaccine. Live attenuated

 Preparations: whole and “split virus” vaccines. “split virus” vaccines are recommended for

children 6 months and older. composition of the vaccine is changed annually.

Influenza Virus

ADMINISTRATION: IM (killed). Live attenuated (intranasal). 1 dose during influenzae season. Children 6months-9 years should receive an

additional dose, 4 weeks after the 1st dose, if not previously immunized.

Influenza Virus

Indications: chronic cardio-respiratory disease

asthma cystic fibrosis bronchopulmonary dysplasia

Influenza Virus

Indications: Sickle cell anemia. Chronic salicylate therapy. Diabetes mellitus. Chronic renal disease. Chronic metabolic disease. immunosuppressive conditions: cancer, HIV etc. Hospital personnel with significant patient

contact.

Influenza Virus

Contraindication: Anaphylaxis to previous dose. Hypersensitivity to eggs.

Adverse Reaction: Soreness at injection site. Allergic response. Guillain-Barré Syndrome.

New Vaccines

Rota virus vaccines Human papilloma virus vaccine