Transcript PHG 413 lecture

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
blood and blood derivatives
allergenic patch tests and extracts
tests to detect HIV and hepatitis
gene therapy products
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 because the
immune system is stimulated to
develop its own immunity against
the pathogen.
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
Antigen
A live or inactivated substance
(e.g., protein, polysaccharide)
capable of producing an immune
response
Antibody
Protein molecules (immunoglobulin) produced by B
lymphocytes to help eliminate an
antigen
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 Vaccines
Inactivated
Live attenuated
viral
bacterial
Inactivated Vaccines
Whole
viruses
bacteria
Fractional
protein-based
toxoid
subunit
polysaccharide-based
pure
conjugate
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
Whole-cell vaccines
Viral
Bacterial
polio, hepatitis A,
rabies, influenza
pertussis, typhoid
cholera, plague
Inactivated Vaccines
Fractional vaccines
Subunit
hepatitis B, influenza,
acellular pertussis,
human papillomavirus,
anthrax,
Toxoid
diphtheria, tetanus
Polysaccharide Vaccines
Pure polysaccharide
pneumococcal
meningococcal
Salmonella Typhi (Vi)
Conjugate polysaccharide
Haemophilus influenzae type b
pneumococcal
meningococcal
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
-measles
- mumps
- rubella
- varicella/zoster
- yellow fever
- rotavirus
- intranasal influenza
- 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
Killed
Attenuated
Toxoid
Subunit
Conjugate
Experimental
Valence
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.