DIFFERENT TYPES OF VACCINES

The technique that is being tested in humans involves the direct injection of plasmids – loops of DNA that contain genes for proteins produced by the organism being targeted for immunity. Once injected into the host’s muscle tissue, the DNA is taken up by host cells, which then start expressing the foreign protein. The protein serves as an antigen that stimulate an immune responses and protective immunological memory.

Enthusiasm for DNA vaccination in humans is tempered by the fact that delivery of the DNA to cells is still not optimal, particularly in larger animals. Another concern is the possibility, which exists with all gene therapy, that the vaccine’s DNA will be integrated into host chromosomes and will turn on oncogenes or turn off tumor suppressor genes. Another potential downside is that extended immunostimulation by the foreign antigen could in theory provoke chronic inflammation or autoantibody production  

Presentation of immunogenic proteins and peptides

Proteins separated from virus particles are generally much less immunogenic than the intact particles. This difference in activity is usually attributed to the change in configuration of a protein when it is released from the structural requirements of the virus particle. Many attempts have been made to enhance the immunogenic activity of separated proteins.  

Adjuvants
Used to potentiate the immune response
  1. Functions to localize and slowly release antigen at or near the site of administration.
  2. Functions to activate APCs to achieve effective antigen processing or presentation
Materials that have been used include;-
  1. Aluminum salts
  2. Mineral oils
  3. Mycobacterial products, eg. Freud’s adjuvants
Immunostimulating complexes (ISCOMS)
  1. An alternative vaccine vehicle
  2. The antigen is presented in an accessible, multimeric, physically well defined complex
  3. Composed of adjuvant (Quil A) and antigen held in a cage like structure
  4. Adjuvant is held to the antigen by lipids
  5. Can stimulate CMI
  6. Mean diameter 35nm

In the most successful procedure, a mixture of the plant glycoside saponin, cholesterol and phosphatidylcholine provides a vehicle for presentation of several copies of the protein on a cage-like structure. Such a multimeric presentation mimics the natural situation of antigens on microorganisms. These immunostimulating complexes have activities equivalent to those of the virus particles from which the proteins are derived, thus holding out great promise for the presentation of genetically engineered proteins.

Similar considerations apply to the presentation of peptides. It has been shown that by building the peptide into a framework of lysine residues so that 8 copies instead of 1 copy are present, the immune response induced was of a much greater magnitude. A novel approach involves the presentation of the peptide in a polymeric form combined with T cell epitopes. The sequence coding for the foot and mouth disease virus peptide was expressed as part of a fusion protein with the gene coding for the Hepatitis B core protein. The hybrid protein, which forms spherical particles 22nm in diameter, elicited levels of neutralizing antibodies against foot and mouth disease virus that were at least a hundred times greater than those produced by the monomeric peptide.  

Immunization and Herd Immunity  

The following questions should be asked when a vaccination policy against a particular virus is being developed.

  1. What proportion of the population should be immunized to achieve eradication.
  2. What is the best age to immunize?
  3. How is this affected by birth rates and other factors
  4. How does immunization affect the age distribution of susceptible individuals, particularly those in age-classes most at risk of serious disease?
  5. How significant are genetic, social, or spatial heterogeneities in susceptibility to infection?
  6. Hoe does this affect herd immunity?

A basic concept is that of the basic rate of the infection R0. for most viral infections, R0 is the average number of secondary cases produced by a primary case in a wholly susceptible population. Clearly, an infection cannot maintain itself or spread if R0 is less than 1. R0 can be estimated from as B/(A-D);B = life expectancy, A = average age at which infection is acquired, D = the characteristic duration of maternal antibodies.

The larger the value of R0, the harder it is to eradicate the infection from the community in question. A rough estimate of the level of immunization coverage required can be estimated in the following manner: eradication will be achieved if the proportion immunized exceeds a critical value pinc = 1-1/R0. Thus the larger the R0, the higher the coverage is required to eliminate the infection. Thus the global eradication of measles, with its R0 of 10 to 20 or more, is almost sure to be more difficult to eradicate than smallpox, with its estimated R0 of 2 to 4. Another example is rubella and measles immunization in the US. Rubella (A = 9 years) has an Ro roughly half that of measles (A = 5 years) and indeed rubella has been effectively eradicated in the US while the incidence of measles have declined more slowly.

Why do we not require 100% coverage to eradicate an infection? Immunization has both a direct and indirect effect. The susceptible host population is reduced by mass immunization so that the transmission of infection has become correspondingly less efficient and eventually, the infection will be unable to maintain itself.

 

Average age
of infection

Epidemic
period

R0

Critical
coverage

Measles 
4-5   
2       
15-17   
92-95
Pertussis  
4-5    
3-4     
15-17   
92-95
Mumps
6-7  
3
10-12 
90-92
Rubella  
9-10 
3-5 
7-8 
85-87
Diptheria 
11-14 
4-6
5-6 
80-85
Polio   
12-15 
3-5 
5-6
80-85
 

 

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