1. Vaccines Surbhi Tak

2. Immunization-Immunity to infectious microorganisms can be achieved by active or passive immunization.
Active
Killed live or attenuated organism injected which can induce immune response
Long term
Immune system plays role
Ex-Hepatitis B vaccine
Diphtheria-pertussis(acellular)-tetanus (DPaT)
Inactivated (Salk) polio vaccine (IPV)
Measles-mumps-rubella (MMR) combined vaccine
Haemophilus influenzae (Hib) vaccine
Passive
Transfer of performed antibodies
Short term
No role of immune system
Ex- diptheria
Hepatitis A &B
Measles
Rabies

3. A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins.
Vaccine is a form of Active immunization

4. History
Edward Jenner-The term vaccine derives from Edward Jenner’s 1796 use of the term cow pox (Latin variolæ vaccinæ, adapted from the Latin vaccīn-us, from vacca cow), which, when administered to humans, provided them protection against smallpox.
Louis Pasteur- generalized Jenner's idea by developing a rabies vaccine, and in the nineteenth century vaccines were considered a matter of national prestige, and compulsory vaccination laws were passed.

5. The Mechanism of a Vaccine
In an ideal scenario, whenever a vaccine is first administered, it is phagocytized by an antigen presenting cell (APC).
Recent research suggest that it is particularly important that the vaccine be taken up by a dendritic cell.
This is because dendritic cells play a key role in activating T cells, which become helper T cells (Th cells).

6. From there, the activated Th cells goes on to activate mature B-cells.
These activated B-cells divides into two cell types, antibody-producing plasma cells and, most importantly, memory B cells.
Memory T-cells are also established, however, they usually have a shorter half-life than memory B cells, thus, they play only a minor role in long-term immunity.
Usually, there are no cytotoxic T-cells formed whenever the body responds to a vaccine.

7. Potential Shortcomings of Vaccines
In some rare cases, a vaccine may directly activate a B cell, without stimulation from Th cells.
Such antigens are known as T-independent (TI) antigens.
The problem with such a response is that only Ig-M antibodies are produced and there are no memory cells established.
Thus, such a vaccine will be useless against establishing immunity.

8. TYPES Killed Attenuated Toxoid Surface molecule
Recombinant vector vaccine
DNA Vaccine
Multivalent subunit Complex
Chimeric vaccine

9. Killed/Inactivated
Some vaccines contain killed, but previously virulent, micro-organisms that have been destroyed with chemicals, heat, radioactivity or antibiotics.
Examples are the influenza vaccine, cholera vaccine, bubonic plague vaccine, polio vaccine, hepatitis A vaccine, and rabies vaccine

10. Heat inactivated Chemical inactivated
Heat inactivation is generally unsatisfactory because it causes extensive denaturation of proteins; thus, any epitopes that depend on higher orders of protein structure are likely to be altered significantly.
Chemical inactivation with formaldehyde or various alkylating agents has been successful. E.g.-Salk Polio vaccine

11. Attenuated
Microorganisms can be attenuated so that they lose their ability to cause significant disease (pathogenicity) but retain their capacity for transient growth within an inoculated host.
Attenuation often can be achieved by growing a
pathogenic bacterium or virus for prolonged periods under abnormal culture conditions. This procedure selects mutants that are better suited to growth in the abnormal culture conditions and are therefore less capable of growth in the natural host.

12. Preparation of Attenuated vaccine
pathogenic bacteria and virus mutants are sel
are grown in abnormal culture ected

13. Toxoid Some species of bacterial produce what is known as exotoxins.
Toxoid are vaccines which consist of exotoxins that have been inactivated, either by heat or chemicals.
These vaccines are intended to build an immunity against the toxins, but not necessarily the bacteria that produce the toxins.
Some examples are botulinum antitoxin and diphtheria antitoxin

14. Recombinant vaccines/Surface molecule
Clone the gene for major surface antigen of hepatitis virus(HBsAg)
Express in yeast cell
Recombinant yeast cells are grown in large fermenters
Yeast cell harvested, disrupted by high pressure
Recombinant HBsAg released& purified
Produce Ab’s
The gene encoding any immunogenic protein can be cloned and expressed in bacterial, yeast, or mammalian cells using Recombinant DNA technology
Example- HepatitisB vaccine

15. Recombinant vector vaccine
Genes that encode major antigens of especially virulent pathogens can be introduced into attenuated viruses or bacteria.
The attenuated organism serves as a vector, replicating within the host and expressing the gene product of the pathogen.
Example -vaccinia vector vaccine

16. DNA Vaccine
DNA vaccines consist of plasmids that contains genes for certain types of antigens
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 fact that muscle cells express low levels of class I MHC molecules and do not express costimulatory molecules suggests that local dendritic cells maybe crucial to the development of antigenic responses to DNAvaccines
Gene gun can also be used for administration

18. DNA Vaccine Non dna vaccine Artificial form One type of immunity
No memory(only in some cases)
Handling problem
Can’t be reused
encoded protein is expressed in the host in its natural form
induce both humoral and cell-mediated immunity
cause prolonged expression of the antigen, which generates significant immunological memory.
Refrigeration is not required for the handling and storage of the plasmid DNA
same plasmid vector can be used for different vaccines

19. Multivalent Subunit Vaccines
Synthetic peptide vaccines
Contain immunodominant B-cell and T-cell epitopes.
Works intra cellularly therefore effective in CTL response
There are number of innovative techniques are being applied to develop multivalent vaccines that can present multiple copies of a given peptide or a mixture of peptides to the immune system-:

20. Solid matrix–antibody antigen (SMAA) complexes
Monoclonal antibodies are attached to solid matrix
Saturate the antibody with desired antigen.
Complex formed can be used as vaccine
Induce both HIR and CMI
Particulate nature therefore increased immunogenicity facilitating phagocytosis

21. Detergent Detergent +protein antigen ->1,2,3
Mixing protein and detergent and then remove detergent from micelle
The individual proteins orient themselves with their hydrophilic residues toward the aqueous environment and the hydrophobic
residues at the centre so as to exclude their interaction with the aqueous environment.
1.ISCOM-Immunostimulating
complexes (ISCOMs) are lipid carriers prepared by mixing protein with detergent and a glycoside called Quil A.
2.Liposome-Liposomes containing protein antigens are prepared by mixing the proteins with a suspension
of phospholipids under conditions that form vesicles bounded by a bilayer.

22. Examples-influenza virus
-measles virus
-hepatitis B virus
-HIV
fuse with the plasma membrane to deliver the antigen intracellularly, where it can be processed by the cytosolic pathway and thus induce a cell-mediated response

23. Chimeric Vaccines
Chimeric vaccines usually consist of attenuated viruses that have been engineered to carry antigens from multiple types of pathogens.
For example, the yellow fever vaccine YF17D has been engineered to carry antigens from HIV, different types of bacteria, malaria, even cancer.
The main adv.of a Chimeric vaccine is the establishment of immunity against several different diseases with one administration

24. Vaccine Production Methods
There are three main vaccine manufacturing strategies:
In-vivo
In-vitro
Chemical Synthesis
Some vaccines can be produced using any one of the three methods while for other vaccines, only one method will work.

25. In-Vivo
In in-vivo manufacturing, the vaccine is produced inside a living organism.
Embryonated Chicken eggs are commonly used, particularly in producing flu vaccines.
Vaccines, such as anti- idiotype, can also be produced in lab animals, such as mice.
There are even some species of plant, such as bananas, that have been genetically engineered to produce a vaccine.

26. In-Vitro
Here, using recombinant DNA technology, vaccines can be produced in yeast cultures, bacterial cultures, or cell cultures.
Recombinant vaccines, such as chimeric vaccines, are produced in this manor.
Attenuated virus/bacteria vaccines can also be produced this way.

27. Chemical Synthesis
Here, instead of using biological systems to produce a vaccine, a vaccine can be produced in a lab.
Vaccines that utilize synthetic peptides as well as conjugated lipids and polysaccharides are manufactured this way.
Usually, this method is used in combination with either in-vivo or in-vitro production.

28. Risks Associated With Vaccines
The primary risk associated with vaccines, especially vaccines that utilize live organisms, is that the vaccine itself causes illness.
This Happened with the orally administered Sabin vaccine for polio, where some individuals became ill and, in rare cases, even spread the illness to other individuals who were not exposed to the vaccine.
Another risk is that the vaccine may behave as a super antigen and over stimulate the immune system.
Yet a third risk is that some individuals may have an allergic reaction to the vaccine, especially vaccines produced in Embryonated chicken eggs and in transgenic plants.

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