This document discusses various types of vaccines, their production methods, and new strategies. It describes several types of vaccines including live, killed, subunit, toxoid, recombinant, synthetic peptide, anti-idiotype, and DNA vaccines. Production methods like egg-based, cell culture-based, and modern recombinant techniques are outlined. New strategies to enhance vaccines like epitope enhancement, prime boost approaches, and various ways to increase CTL avidity are also summarized. Adjuvants and vaccines still under development for respiratory infections, HIV/AIDS, HPV, and meningococcal meningitis are briefly mentioned.

1. Done by,
P. MEENALOKSHINI
VACCINES– TYPES , PRINCIPLE OF
PRODUCTION, CONVENTIONAL AND
MODERN PRODUCTION, NEW STRATEGIES
VACCINES, UNDER DEVELOPED VACCINES,
ADJUVANTS
Done by,
P. MEENALOKSHINI
II MSc Biochemistry

2. INTRODUCTION
1. A vaccine – preparation-killed or weakened microorganism –
immunize people when given orally or injected- to prevent
diseases.
2. Edward jenner- developed principle of vaccination (1796)–
invention on- vaccine against small pox.
3. The process of producing state of immunity- individuals-
immunization. It is of two type:
Active immunization
Passive immunization

3. TYPES OF VACCINES
1. Live
vaccines
2. Killed
whole
organism
vaccines
3. Subunit vaccines
4. Toxoids
vaccines
5. Recombinant
virus vaccines
6. Synthetic peptide vaccines
7. Anti idiotype
vaccines
8. DNA vaccines

4. LIVE VACCINES
1. Attenuated vaccines – bacteria/ virus- abnormal culture condition-
long periods- avirulent.
2. Example- BCG vaccines from Mycobacterium bovis – medium
with increased concentration of bile -2 weeks incubation- loss
virulence.
3. Similarly, typhoid, MMR vaccines are prepared.
4. Advantage
a. 1 initial dose- rarely additional
b. Local immunity
c. Less expensive
d. Provides - protection
Disadvantage
Mutate- virulent form
Risk- abortion/ transient infertility
Exacerbate- immuno suppressed
animals .

6. KILLED VACCINES
1. Growing- killing / inactivating –heat/chemicals.
2. Example- salk vaccines and whooping cough – formaldehyde
inactivation.
3. Rabies vaccines- grown-human fibroblasts.
4. Advantage
a. Wide varieties of diseases
b. No risk- reverting
c. Little-abortion
d. Stable-storage
e. Stimulant- colostrums
Disadvantage
Allergic reactions
2 initial doses- 10days apart
Slower immunity
Expensive than live

8. SUBUNIT VACCINES
1. Purified one or 2 proteins/ polysaccharides coat of
organism- vaccines.
2. Example- purified heamagglutinins- influenza vaccines.
Multivalent subunit vaccines
3. Multiple copies of any peptides/ mixture of peptide.
Solid matrix antibody-antigen
Detergent
Micelles

10. TOXOID VACCINES
1. Purifying- bacteria exotoxin( diptheria and tetanus toxins) -
inactivate-formaldehyde –toxoid vaccines.
2. Vaccination- induce- antibody- against toxoid- binding-
toxin- neutralize.
3. Example- Tetanus Toxoid

11. RECOMBINANT VIRUS VACCINES
1. Gene encodes antigen of pathogens- introduced into- attenuated
bacteria/viruses. These –vectors-replicate-express gene product of
pathogen.
2. Genetic engineering-gene coding for immunogenic protein from
one-another genome.
3. Example- Vaccinia virus vaccines
4. Genes- Hepatitis B, Herpes simplex virus, Influenza viruses-
vaccinia virus.
5. Induces antibody and cell mediated immunity.

13. SYNTHETIC PEPTIDE VACCINES
1. DNA –encodes protein antigen-pathogen-inserted-plasmid-
amplified-vaccines.
2. Injected- subjects
3. Cells of subject accept DNA – transcribe- translate- proteins.
These proteins moves to cell membrane surface- stimulate-
Immune response- humoral & cell mediated immunity.
Example – bacteria- diptheria & cholera
4. Advantage
a. Stable-cheap
b. Less-quality assurance
Disadvantage
Side effects
Poorly immunogenic

15. ANTI IDIOTYPE ANTIBODY
1. Variable region – number of antigen like segments-idiotype-
trigger complementary antibody- anti idiotype.

16. DNA VACCINES
Gene coding target antigen-transcriptional control of promoter-
cell mediated & antibody mediated response.
Cell mediated response
1. Plasmid-taken up by APC- dentritic cells.
2. Genes-transcribed-translated.
3. Products-degraded-peptides
4. Exposed-cell surface
Antibody mediated response
1. Plasmid taken up- muscle cells.
2. Protein-synthesized- released- engulfed- APC.
3. Proteins-degraded in class II & presented to Th cells-
lymphokines- aid B cells – antibodies.

17. PRINCIPLES OF VACCINES
PRODUCTION
1. Live attenuated vaccines- organisms- laboratory condition-
lose its virulence.
2. Attenuation- heat/passage of virus in foreign host-
embryonated eggs/ culture cells.
Example- Sabin polio vaccines-attenuation- high inocula-
passage in primary monkey kidney cells.
1. Inactivated vaccines- kill organisms-chemical/heat.
2. Current approach- gene techniques- instead bacteria/ virus,
single gene- expressed- foreign host- cloning- induces-vector-
produce antigen purified + adjuvants- safe & effective.
Example- Gardasil.

18. PRODUCTION OF
CONVENTIONAL VACCINES
1. Egg based vaccine production
2. Cell culture based vaccine production.
EGG BASED VACCINE PRODUCTION EX- FLU VACCINES
Strains of flu vaccines- injected- fertilized eggs- incubated-
harvested- purified strains- blended into one vaccine- FDA license-
packaged.
Disadvantage
Large number of chicken eggs required.
Longer time
Not administered to allergens.

20. CELL CULTURE BASED VACINE
PRODUCTION
Mammalian cell culture ex- flu vaccines
1. Carried out – serum free media- intact virus-isolated using
affinity chromatography- purified-blended- license-
packaged.
2. Example- 3 FDA licensed vaccines Flucelvax, Preflued,
celvapan.

22. MODERN VACCINE PRODUCTION
1. Hepatitis B
2. AIDS
3. Vibrio cholera
4. Vaccinia virus
5. Vaccinia virus vector- flu vaccines

23. HEPATITIS B

24. AIDS

25. VIBRIO
CHOLERA

26. RECOMBINANT
VACCINIA VIRUS

27. RECOMBINANT
VACCINIA VECTOR-
FLU VACCINES

28. NEW STRATEGIES VACCINES
EPITOPE
ENHANCEMENT
1. Develop- better
vaccines- making-
antigenic peptide-
immunogenic-
increasing affinity of
a peptide-virus or
tumor- MHC.
2. Example- peptides-
HIV & HCV –binds
– specific class I
HLA molecules-
protection- against
virus & tumors.

29. PRIME BOOST APPROACH
1. Immunization of individual with 2/more doses- prime boost
regime.
2. Vaccine– same formulation- homologous prime boost.
3. Vaccine- different formulation- heterologous prime boost-
administration of same antigen- different ways- purified-
recombinant protein-adjuvant- as live, virus/ bacterial vector.
4. Prime boost strategies- development of vaccines- HIV, TB &
malaria.
VARIOUS PLOYS FOR ENHANCING CTL AVIDITY
1. High-avidity CTL- effective at clearing viruses and
destroying cancer cells than low-avidity CTL.

30. VACCINES UNDER DEVELOPMENT
ACUTE RESPIRATORY INFECTION
1. Both virus& bacterial- causes. Pathogens are RSV
( respiratory Syncytial virus) & Streptococcus pneumoniae.
2. In 2003- emergence of typical pnuemoniae- China-
identified- SARS.
3. Development of vaccines against SARS – global priority-
early clinical stages.
HIV / AIDS
1. HIV – Lentiviral group- retroviridal family.
2. 2 types- HIV1 & HIV2. HIV1 is aggressive – spread rapidly.
3. Highly reactive antiretrovial therapy- reduced progression &
transmission. However, treatment- progresses prevention.

31. 4. Recombinant adenovirus – when combined with recombinant
canary pox- prime boost vaccinations- control in viral replication.
5. The development of safe & effective HIV vaccines –
hampered- tremendous genetic variability of the virus.
HUMAN PAPILLOMA VIRUS (HPA)
1. HPV- cervial cancer. Belongs- Papovaviridae family. 30
types- infect genital mucosa.
2. Cancer gene-HPV DNA with oncogenes. The association of
cervial cancer with sexually transmitted HPV DNA –
substantiated vaccine production.

32. MENINGOCOCCAL MENINGITIS
1. Bacterial meningitis- global threat.
2. Nisseria meningitidis – cause- bacterial meningitis-
spread- airborne liquid droplets of infected persons.
3. Polysaccharide vaccines against N meningitidis –
available. However, poor immunogens- fail to induce
immunological memory.
4. Vaccines – produced- found to be 50% to 80% effective.

33. ADJUVANTS
Substances – administered- specific antigen- enhance immune
response to that antigen- inactivated or purified antigen vaccines-
adjuvants.
Types
Aluminium salts
Used in Hepatitis B , diptheria, polio, rabies & flu vaccines.
Promote- good antibody response- poor cell mediated response.
Advantage- safe & effective
Disadvantage- induction of granulomas at injection site- variation
of alum preparation.

34. Liposomes & immuno stimulating
complexes
Properties
1. Vaccine vehicle
2. Composed- adjuvant-Quail A- antigen in cage like structure.
3. Adjuvant- held to antigen- lipids.
4. Stimulate CMI,DH & CTL response.
5. ISCOMS- multimeric presentation of antigen- strong
adjuvant- effective- mucosal immunization.
6. Preparation – solubilize amphipathic proteins in non-ionic
detergent-addition of quillaia saponins, Cholesterol,
phospholipids .

35. Complete Freund’s adjuvant
(FCA)
Incomplete Freund’s
adjuvant (FIA)
It consists of heat killed
Mycobacterium tuberculosis in
non metabolizable oils (
paraffin oils).
In simple – water in oil
emulsion + M. tuberculosis.
FIA lacks mycobacterial
components. Water in oil
emulsion only.
On injection with FCA induces
Th1 dominant response, in
which cell mediated immunity
is enhanced against viruses &
bacteria.
On injection with FIA induces
Th2 dominant response, in
which humoral mediated
immunity is enhanced against
bacteria, toxins & allergens.

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