Vaccines work by exposing the immune system to harmless or inactive forms of pathogens to induce protective immunity. First generation vaccines used whole pathogens that were either live-attenuated or killed. While live vaccines induce broad immune responses, there is a risk of reversion; killed vaccines require multiple doses but are safer. Second generation subunit vaccines use isolated protein antigens to generate specific responses without risks of live vaccines. Third generation DNA vaccines contain genetic code for antigens, inducing immune responses through host cell expression without using live pathogens.

1. Vaccinology

2. Vaccine is a biological preparation that tricks our
body to make antibodies against a form of
inactive or harmless form of pathogen so that
when the body encounters the real and
dangerous pathogen the body is now ready to
protect it’s cells.
Vaccine is derived from the word ‘Vacca’

4. History of vaccine
6h century in China
Dried scabs of small pox was blown into nostrils of immunocompromised individuals

5. Variolation
Variolation (10th century) was the method of deliberate
inoculation to immunize healthy individuals against smallpox
(Variola) with dried pus taken from a patient or a recently
variolated individual, in the hope that a mild, but protective,
infection would result.
Variolation is no longer used today. It was replaced by the
smallpox vaccine, a safer alternative. This in turn led to the
development of the many vaccines now available against
other diseases.

6. Lady Montagu advocated and introduced Variolation from Ottoman
empire to England

18. Preparation of Attenuated Vaccines

19. Passive Immunization
• Can occur naturally via transfer of maternal antibodies across placenta to fetus
• Injection with preformed antibodies
– Human or animal antibodies can be used
– Injection of animal Ab’s prevalent before vaccines
• Effects are only temporary

20. Conditions Warranting Passive
Immunization
1. Deficiency in synthesis of Ab as a result of congenital or acquired B-cell
defects
2. Susceptible person is exposed to a disease that will cause immediate
complications (time is the biggest issue)
3. Disease is already present

21. Common Agents For Passive Immunization

22. The Immune System and Passive
Immunization
• The transfer of antibodies will not trigger the immune system
• There is NO presence of memory cells
• Risks are included
• Recognition of the immunoglobulin epitope by self immunoglobluin paratopes
• Some individuals produce IgE molecules specific for passive antibody, leading to
mast cell degranulation
• Some individuals produce IgG or IgM molecules specific for passive antibody,
leading to hypersensitive reactions

23. Active Immunization
• Natural Infection with microorganism
or artificial acquisition (vaccine)
• Both stimulate the proliferation of T
and B cells, resulting in the formation
of effector and memory cells
• The formation of memory cells is the
basis for the relatively permanent
effects of vaccinations

24. Principles Underlying Vaccination
• Concept of Immunity
– Self vs. Non-self
– Antigen specificity
– Indicated by presence of effector cells
– Protection from infectious diseases using above
methods

25. Vaccinations
Boosters (multiple inoculations) are required
Interference of passive maternal antibodies

26. Effectiveness of Vaccinations
• Small percentage of recipients will respond poorly
– Role of genetic determinants
• Herd Immunity
– Majority of population is immune, so chance of susceptible individual
contacting infected individual is low
– Measles Epidemic

27. Herd Immunity
• Factors affecting herd immunity
– Environmental Factors: crowded conditions, seasonal variations
– Strength of Individual’s Immune System
– Infectiousness of Disease: greater the risk of infection, the higher percentage
of people need vaccines to attain herd immunity
• When enough people are vaccinated, chance of germ infecting the non-
immunized population is small
• Can lead to disappearance of diseases (smallpox)
– Vaccination no longer necessary

28. Quantitative Data

29. Further Proof of the Effectiveness of
Vaccines

30. Development of Vaccines
• Common misconception that activation
of the immune system results in protective
immunity
• Multiple factors affect decisions when
making vaccines
1. Activation of specific branch of
immune system
2. Development of
immunological memory

31. Role of Memory Cells
• Depends on incubation period of pathogen
– Short Incubation Periods
• ex. Influenza
• Symptoms already under way by the time memory cells are
activated
• Repeated immunizations with neutralizing antibodies
– Long Incubation Periods
• ex. Poliovirus
• Enough time to allow memory B cells to respond

32. Immunological Memory vs. Serum
Antibody Levels

33. Types of Vaccines
• Whole-Organism
– Attenuated Viral/Bacterial
– Inactivated Viral/Bacterial
• Purified Macromolecules
– Polysaccharide
– Toxoid
– Recombinant Antigen
– Recombinant-Vector
• DNA
• Synthetic Peptide
• Multivalent Subunit

34. Whole-Organism Vaccines
• Many common vaccines used consist of
inactivated or attenuated bacterial
cells or viral particles
• Includes attenuated and inactivated
vaccines

35. Attenuated Viral or Bacterial Vaccines
• Attenuation – to reduce in force, value, amount, or degree; weaken
– Achieved by growth under abnormal culture conditions
– Bacillus Calmette-Guerin (BCG)
– Act as a double edged sword, as they have distinct advantages and
disadvantages…

36. Advantages of Attenuated Bacterial or Viral
Vaccines
• Advantages stem from their capacity for transient growth
• Prolonged immune-system exposure
• Single immunizations
• Replication within host cells

37. Exception to the Rule…
• Sabin Polio vaccine consists of 3 attenuated strains of poliovirus
• Colonization of intestine results in immunity to all 3 strains
– Production of secretory IgA and induction of IgM and IgG
• Result is the need for boosters
– Individual strains interfere with one another
• First immunization  one strain predominates in growth
• Second Immunization  immunity generated by previous immunization
limits growth of previously predominant strain
• Third Immunization  same principle as second immunization

38. Disadvantages of Attenuated Bacterial or
Viral Vaccines
• MAJOR disadvantage is possible reversion
– ex: Rate of reversion of Sabin Polio vaccine is one case in 4 million doses
• Presence of other viruses as contaminants
• Unforeseen postvaccine complications

39. The Future of Attenuation…
• Genetic engineering techniques provide new methods of attenuation
• Herpes virus vaccine for pigs
• Possible elimination of reversion?

40. Inactivated Viral or Bacterial Vaccines
• Methods of inactivation include heat or chemical agents
– End result…. Loss of replication ability
• Difficult to inactivate due to potential for denaturation of epitopes
– Dependence on higher order levels of protein structure

41. Attenuation vs. Inactivation

42. Attenuation vs. Inactivation
• Attenuation
– Normally require one dosage to induce relatively permanent immunity
– Primarily cell-mediated in nature
– Despite reliance on cell-mediated immunity, increased IgA response
• Inactivation
– Requires multiple boosters
– Emphasis on activating humoral immunity
However, something very important is missing….

43. First Generation Vaccines
First generation vaccines are whole-organism vaccines – either live
and weakened, or killed forms. Live, attenuated vaccines, such as smallpox
and polio vaccines, are able to induce killer T-cell (TC or CTL)
responses, helper T-cell (TH) responses and antibody immunity.
However, attenuated forms of a pathogen can get converted to a
dangerous form and may cause disease in immunocompromised vaccine
recipients (such as those with AIDS).
While killed vaccines do not have this risk, they cannot generate
specific killer T cell responses and may not work at all for some
diseases.
[Attenuated + Killed]

44. Second Generation Vaccines
Subunit vaccines are the Second generation vaccines and were
developed to reduce the risks from live vaccines. These are subunit vaccines,
consisting of specific protein antigens (such as tetanus or diphtheria toxoid)
or recombinant protein components (such as the hepatitis B surface
antigen).
They can generate TH and antibody responses, but not killer T cell
responses.

45. Third Generation Vaccines
DNA vaccines are third generation vaccines. These vaccines contain DNA
that codes for specific proteins (antigens) from a pathogen. The DNA is
injected into the body and taken up by cells, whose normal metabolic processes
synthesize proteins based on the genetic code in the DNA that they have taken up.
Because these proteins contain regions of amino acid sequences that are
characteristic of bacteria or viruses, they are recognized as foreign and when they
are processed by the host cells and displayed on their surface, to triggers
immune responses.
Alternatively, the DNA may be encapsulated in protein to facilitate cell
entry. If the DNA is encapsulated in the capsid protein, the resulting vaccine can
combine the potency of a live vaccine without reversion risks.