Biologics

Biologics Wide 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: vaccines vaccines blood and blood derivatives allergenic patch tests and extracts allergenic patch tests and extracts tests to detect HIV and hepatitis tests to detect HIV and hepatitis gene therapy products gene therapy products cells and tissues for transplantation, cells and tissues for transplantation, new treatments for cancers, arthritis, and other serious diseases.

Vaccine 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 Passive immunotherapy Injection Boosters Active immunization Time Initial inoculation Antibody (IgG, IgM) concentration (titer)

Principles of Vaccination A live or inactivated substance (e.g., protein, polysaccharide) capable of producing an immune response Protein molecules (immuno- globulin) produced by B lymphocytes to help eliminate an antigen Antigen Antibody

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.immune system

Classification of Vaccines Inactivated Live attenuated viral viral bacterial bacterial

Killed Vaccines containing killed microorganisms – these are previously virulent micro-organisms which have been killed with chemicals or heat. Examples are vaccines against flu, cholera, bubonic plague, polio and hepatitis A. Attenuated Some vaccines contain live, attenuated microorganisms. The organism has been cultured so as to reduce its pathogenicity, but still retain some of the antigens of the virulent form. They typically provoke more durable immunological responses and are the preferred type for healthy adults. Examples include the viral diseases yellow fever, measles, rubella, and mumps and the bacterial disease typhoid. The live Mycobacterium tuberculosis vaccine developed by Calmette and Guérin is not made of a contagious strain, but contains a virulently modified strain called "BCG" used to elicit immunogenicity to the vaccine.

Live Attenuated Vaccines Attenuated form of the "wild" virus or bacterium Must replicate to be effective Immune response similar to natural infection Usually effective with one dose

Live Attenuated Vaccines Severe reactions possible Interference from circulating antibody Fragile – must be stored and handled carefully

Inactivated Vaccines Cannot replicate Generally not as effective as live vaccines Less interference from circulating antibody than live vaccines Generally require 3-5 doses Antibody titer may diminish with time

Inactivated Vaccines virusesbacteriaprotein-based toxoid toxoid subunit subunitpolysaccharide-based pure pure conjugate conjugate Whole Fractional

Toxoid In some diseases, diphtheria and tetanus are notorious examples, it is not the growth of the bacterium that is dangerous, but the protein toxin that is liberated by it. Treating the toxin with, for example, formaldehyde, denatures the protein so that it is no longer dangerous, but retains some epitopes on the molecule that will elicit protective antibodies.

Subunit Protein subunit – rather than introducing an inactivated or attenuated micro-organism to an immune system (which would constitute a "whole-agent" vaccine) A fragment of it can create an immune response. Examples include : the subunit vaccine against Hepatitis B virus that is composed of only the surface proteins of the virus (previously extracted from the blood serum of chronically infected patients, but now produced by recombination of the viral genes into yeast), the virus-like particle (VLP) vaccine against human papillomavirus (HPV) that is composed of the viral major capsid protein, and the hemagglutinin and neuraminidase subunits of the influenza virus.

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

Immunisation Department, Centre for Infections Carrier protein Polysaccharide linked to carrier protein Conjugate vaccine Bacteria 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

Valence Vaccines may be monovalent (also called univalent) designed to immunize against a single antigen or single microorganism or multivalent (also called polyvalent). designed to immunize against two or more strains of the same microorganism, or against two or more microorganisms. In certain cases a monovalent vaccine may be preferable for rapidly developing a strong immune response.

Immunisation Department, Centre for Infections Vaccine composition In 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 immunity The immune system recognizes vaccine agents as foreign, destroys them, and 'remembers' them. When the virulent version of an agent comes along the body recognizes the protein coat on the virus, and thus is prepared to respond, by (1) neutralizing the target agent before it can enter cells, and (2) by recognizing and destroying infected cells before that agent can multiply to vast numbers.

When two or more vaccines are mixed together in the same formulation, the two vaccines can interfere. This most frequently occurs with live attenuated vaccines, where one of the vaccine components is more robust than the others and suppresses the growth and immune response to the other components.

Effectiveness Vaccines do not guarantee complete protection from a disease. Sometimes this is because the host's immune system simply doesn't respond adequately or at all. This may be due to a lowered immunity in general (diabetes, steroid use, HIV infection) or because the host's immune system does not have a B cell capable of generating antibodies to that antigen. Even if the host develops antibodies, the human immune system is not perfect and in any case the immune system might still not be able to defeat the 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 vaccine is dependent on a number of factors: the disease itself (for some diseases vaccination performs better than for other diseases). the strain of vaccine (some vaccinations are for different strains of the disease). whether one kept to the timetable for the vaccinations. some individuals are 'non-responders' to certain vaccines, meaning that they do not generate antibodies even after being vaccinated correctly. other factors such as ethnicity or genetic predisposition.

Compulsory Vaccines Compulsory 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 OPV2 drops orally eIPV SC injection PRECAUTIONS & CONTRAINDICATIONS(CI) (a) OPVpregnancy, immunodeficiency (b) IPVneomycin hypersensitivity ADVERSE REACTIONS OPVparalytic 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 > C 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 areas Chronic liver disease Hemophilia

Hepatitis A ADMINISTRATION: IM injection 2 doses, at least 6 months apart ADVERSE REACTIONS: Local reactions, fever Rare: anaphylaxis

Additional 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, myalgia Anaphylactic 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 1 st 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