Vaccination
MLS 451
NOV 2022
Introduction (immunological memory)
Recollection of a former encounter alters subsequent response
to same stimulus.
Immune system remembers a former pathogen and responds
to a second challenge differently from the first .
Re-exposure to that same stimulus often causes a quicker
response to prevent subsequent infection.
This is because memory immune cells are established after the
initial encounter.
The goal of vaccination is to trigger an immune response more
rapidly and with less harm than a natural infection.
In essence, to avoid the disease that often accompanies the
first exposure while enabling establishment of long-lasting
Vaccine basics
Vaccines work because of immune memory
(recalls identity of a specific pathogen long after
first encounter.
Active
Immunization Passive (Adoptive transfer)
Active: use of attenuated / killed pathogen/ purified
pathogen protein preparations to induces immune
mediated resistance to infection or disease.
Passive : introduces components of the immune
response (e.g., antibodies or stimulated immune cells)
obtained from an appropriate donor(s) directly into the
patient.
Vaccine basics (Practical considerations)
Vaccines must be safe, efficacious and practical.
Safety is paramount since vaccines are given to large no of
people some of whom may never be exposed to the virus
targeted.
Herd immunity: To be effective, a vaccine must induce protective
immunity in a fraction of the population that is sufficient to
impede person-to-person transmission.
80 to 85%, for smallpox, 93 to 95% for measles.
No vaccine is 100% effective : level of immunity is not equal to
the no of people vaccinated.
Non responders to vaccination: implication for vaccine success.
Vaccine basics contd
Practical issues like stability, ease of administration,
cost plays an important role.
Public acceptance and complacency are very important
issues in the overall vaccine success.
Challenges to vaccine efficacy
1. Poverty and economic challenge
2. Societal view of health care
3. Lack of trust in the government
4. Poor local health care system infrastructure
How to make vaccines
SCIENCE AND ART OF MAKING VACCINE
Different technologies: main requirements include
Isolation/ Construction of an immunogenic agent with
low pathogenic potential, able to induce a lasting,
protective immune response. Serial passages in unnatural host
Growth at non physiologic temp
SAVE
Live attenuated vaccine Mixing infectious with non- infectious
virus or using RecDNA Tech
Problems
◦ pathogen shedding
◦ Reversion
◦ Atypical infections
◦ Contamination
SCIENCE AND ART OF MAKING VACCINE Contd
Chemical e.g Formalin
Killed /Inactivated Vaccines
Physical e.g Heat
Treatment eliminates infectivity
but does not compromise Problems
antigenicity. May not induce T cell response which
is critical in virus clearance.
Using chemical (formaldehyde, non-
ionic detergents) or growth in an Incomplete or excessive inactivation.
unnatural host etc
These vaccines are safe as the
treated organisms cannot
reproduce or revert.
However, often requires the
administration of multiple doses
Non-recombinant Purified Subunit Vaccines
Vaccines formulated with purified components of
pathogens, rather than the intact organisms , are called
subunit vaccines. Eg HBV vaccine, split influenza vaccines.
Use protein that are recognized by the immune system.
Safe in principle, thus forming basis for safe vaccine.
Determining which proteins to include in a vaccine is
accomplished by selecting those that are recognized by
Abs and Tc Cells.
This selection can be determined by assessing the
immune responses of individuals who have recovered
from the disease.
Pitfall
Peptide vaccines have had little success, mainly due to
cost: synthetic peptides are expensive to make in
sufficient quantity.
Antibody response is often weak and short lived.
Given the likely simplicity of the host-anti peptide
response (usually a single epitope is contained within
the peptide)might select for IEM.
Recombinant subunit vaccine(adjuvant required)
Synthetic peptide produced in the lab & expressed
using expression system.
VLPs : structural proteins are expressed, and they self
assemble. immunogenic but not infectious.
Nucleic vaccines: (viral protein made de novo)
pathogen DNA/ mRNA are engineered to initiate the
expression of a protein specific to the disease.
Inject the NA, the host cells take up the NA and is
translated within the host cell.
rec DNA Approaches to Subunit Vaccines
Allows cloning of selected genes into nonpathogenic
viruses, bacteria, yeasts, insect cells, or plant cells to
produce the immunogenic protein(s).
As only a portion of the desired genome is required for
such production, there can be no contamination of the
resulting vaccine with the original pathogen.
Eg Flublok, large qtys of the HA protein of 3 most
prominent influenza Viruses are synthesized from
baculovirus Vectors in a preservative- and egg-free cell
culture system.
Virus-Like Particles
The capsid proteins of non-enveloped and of some enveloped virus
particles may self-assemble into virus-like particles.
These particles have capsid-like structures that are virtually identical to
those in virus particles.
Unlike viral particles, these capsids are empty: they contain no genetic
material and cannot propagate.
VLP vaccines often induce durable neutralizing antibodies and other
protective responses.
The particles are completely noninfectious, inactivation with formalin
or other agents is not required.
Immunogenicity therefore is not compromised and concerns about
efficiency of inactivation are avoided.
DNA Vaccine
plasmid DNA encoding antigenic proteins is injected
directly into the muscle of the recipient.
Muscle cells take up the DNA and the encoded protein
antigen is expressed, leading to both a humoral
antibody response and a cell-mediated response.
The DNA appears either to integrate into the
chromosomal DNA or to be maintained for long periods
in an episomal form.
Comparison of attenuated (live),
inactivated (killed), and DNA vaccines
Adjuvants
Inactivated vaccine or purified proteins often do not induce
the same immune response live organisms.
Substance(Adjuvants) that stimulates the early inflammatory
response can help in boosting immunogenecity.
They act by stimulating early intrinsic and innate defense
signals, which then shape subsequent adaptive responses.
They act by presenting antigens as particles, by
sequestering antigen at the site of inoculation, and by
directly stimulating the intrinsic and innate immune
responses.
Eg complete Freund’s adjuvant, aluminum salts, alum etc
Delivery and formulation
Delivery by injection has many disadvantages, and
therefore improvement of the administration of
vaccines is an important goal of manufacturers.
At present, vaccines are delivered by a limited number
of methods, including :
the traditional hypodermic needle injection
oral administration
air gun injection of liquid vaccines under high pressure
Nasal sprays etc
SARS CoV 2 Vaccine Approaches
In the context of SARS CoV 2
In the context of SARS CoV 2
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