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.

Recombinant DNA technology rDNA is a form of DNA that does not exist naturally. Created by combining DNA sequences that would not normally occur togethe. Insulin Erythropoetin Growth hormone

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.

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

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

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

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 Viral polio, hepatitis A, rabies, influenza Bacterial pertussis, typhoid cholera, plague Whole-cell vaccines

Inactivated Vaccines Subunit hepatitis B, influenza, acellular pertussis, human papillomavirus, anthrax, Toxoid diphtheria, tetanus Fractional vaccines

Polysaccharide Vaccines pneumococcalmeningococcal Salmonella Typhi (Vi) Haemophilus influenzae type b pneumococcalmeningococcal Pure polysaccharide Conjugate polysaccharide

Pure Polysaccharide Vaccines Not consistently immunogenic in children younger than 2 years of age No booster response Antibody with less functional activity Immunogenicity improved by conjugation

Live Attenuated Vaccines Viral - measlesViral - measles - mumps - mumps - rubella - rubella - varicella/zoster - yellow fever - varicella/zoster - yellow fever - rotavirus - rotavirus - intranasal influenza - intranasal influenza - oral polio - oral polio Bacterial BCG, oral typhoid

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.

Types KilledAttenuatedToxoidSubunitConjugateExperimentalValence

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.

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. Not all toxoids are for micro-organisms; for example, Crotalus atrox toxoid is used to vaccinate dogs against rattlesnake bites

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.

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.