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LECTURE 2

The document discusses the complexities of vaccine development, highlighting the need for extensive research, regulatory human trials, and the potential for adverse side effects. It explains the concepts of active and passive immunization, the importance of herd immunity, and various types of vaccines including live attenuated, inactivated, recombinant vector, subunit, conjugate, and DNA vaccines. Additionally, it addresses the use of adjuvants to enhance immune responses and the role of preservatives in vaccines.

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Bijay Bista
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5 views

LECTURE 2

The document discusses the complexities of vaccine development, highlighting the need for extensive research, regulatory human trials, and the potential for adverse side effects. It explains the concepts of active and passive immunization, the importance of herd immunity, and various types of vaccines including live attenuated, inactivated, recombinant vector, subunit, conjugate, and DNA vaccines. Additionally, it addresses the use of adjuvants to enhance immune responses and the role of preservatives in vaccines.

Uploaded by

Bijay Bista
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
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BIOT 411-VACCINE DEVELOPMENT AND PRODUCTION

INTRODUCTION
LECTURE 2
Developing a vaccine
⦿ Lots of research
○ Time consuming, costly
○ Idea is to isolate a component of the organism
that proves to be immunogenic-sometimes not
possible
⦿ Human trials are strictly regulated
⦿ Might have vaccine developed but there
might be adverse side effects – can’t be
used.
⦿ Immunity can be achieved by active or
passive immunization
⦿ Passive – transfer of preformed
antibodies
⚫ Maternal antibodies to fetus
⚫ Antibody therapy for bites, immunodeficiency

⦿ Active – long term protection,


immunologic memory, actual exposure
⚫ Coming into contact with any foreign substance
⚫ Vaccines
Passive immunization is
only temporary, the
antibodies will only last
so long, but it can help
someone recover from a
current infection

To achieve lifetime
immunity, it must be
through active
immunization
⦿ There is a chance of side effects in small # of
population
⦿ That is the case with any treatment/drug
⦿ However, if the benefits to the population
out-weigh the risk of side effects, vaccines must
be used to protect the majority of the population
⦿ HERD IMMUNITY is important!!!!
⦿ There might be some people who cannot be
vaccinated (due to having cancer or some other
condition, allergies)
⦿ Also, just because you got the vaccine, it doesn’t
mean it worked in you
HERD IMMUNITY
⦿ Vaccine efficacy is the reduction in incidence of a
disease amongst those who have been vaccinated
relative to the incidence in the unvaccinated.
⦿ Because biologicals are inherently variable,
individuals do not respond identically to vaccines.
⦿ Vaccines may fail to induce immunity in a few
individuals. But the most effective vaccines induce
a protective immune response in > 95% of
individuals.
⦿ If a high level of vaccination coverage is achieved
with an effective vaccine, disease transmission
can be interrupted.
⦿ When disease transmission is interrupted, even
those individuals who were not vaccinated, or
who were vaccinated and did not develop
immunity, will be protected from disease.

⦿ This effect is known as herd immunity.

⦿ Smallpox was eradicated by achieving sufficient


immunization coverage to prevent the
transmission of disease to unvaccinated (non
immune) susceptibles.
Designing Effective
Vaccine
⦿ Protective immunity must be achieved
○ Must pay attention to how the antigen activates the
humoral and cell-mediated branches

⦿ Must produce immunologic memory


○ Vaccine that produces primary response but fails to
produce secondary response is not effective
Live, Attenuated Vaccines
⦿ Microorganisms can be attenuated so that
they lose ability to cause significant disease
○ Retain capacity for growth in host
○ Bacteria is grown for prolonged period in adverse
conditions. Those that survive will not be suited to
grow in “better” conditions in host
○ A virus might be grown in cell type that is not normal
host
○ Accumulates mutations that might weaken it
○ Measles, mumps, rubella vaccine is example
Live, Attenuated Vaccines
Advantages Disadvantages
⦿Possibility that it will revert to
⦿Can grow in host
virulent form (Polio – 1 in 2.4
therefore producing million chance this will happen)
immunologic memory ⦿Complications
with only single ⚫ Measles vaccine – encephalitis
⚫ Out of 75 million patients
vaccination between 1970 and 1993, only
48 cases
⦿Produces memory T cells
⦿Good for distribution in However, risks from remaining
un-vaccinated and getting
Third World countries disease is much greater than
complications to these proven
vaccines
Inactivated or “killed” vaccines
⦿ Inactivation of pathogen by heat or chemical means
○ Not capable of replication in host
○ Epitopes have to be maintained after killing process
○ Often require boosters

⦿ Risks
○ Pathogen has to be grown in large #’s prior to
inactivation – individuals involved in manufacturing
are at risk
○ Some of the pathogen may not be killed

⦿ Pertussis vaccine, typhoid vaccine


Recombinant vector vaccine

⦿ Viruses and other


microbes that
replicate in cells but
don’t cause disease
can be used to
deliver fragments of
a pathogenic
microbe for
vaccination
Subunit Vaccines
⦿ Purified macromolecules derived from
pathogens
⦿ Toxoids
○ Some bacteria are pathogenic because of
exotoxins that they produce
○ Purify exotoxin, inactivate it with formaldehyde to
form toxoid that can be used to immunize
○ The immune system is then able to neutralize the
toxin when an infection occurs
Conjugate Vaccines
⦿ When subunit
vaccines are poor
immune stimulators,
they can be coupled
with strong immune
activators
⚫ Example – take
polysaccharide found on
Haemophilus influenzae
(not immunogenic) with
tetanus toxoid which is
highly immunogenic
⚫ Results in immunity to
Haemophilus
DNA Vaccines

Clinical trials for HIV, Hepatitis, Influenza, etc.


⦿ Adjuvants are used to enhance the immune
system’s response and time with the
immunogen
○ Virosome – reconstituted virus envelope without
any genetic information
- Used in influenza vaccine and hep A vaccine

○ AS04 – alum salt containing LPS (highly


recognized by TLR4)

○ Freund’s incomplete adjuvant – used in research


⦿ Preservatives in vaccine vials
○ Thimerosal
- It’s ethylmercury - NOT methymercury (bad, kind that
builds up in fish and can be toxic to humans)
REFERENCES
⦿ KUBY’S IMMUNOLOGY:
⦿ CHAPTERS:
RESPONSE TO INFECTIOUS DISEASES
VACCINE

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