Bacterial, Viral, Polysaccharides, Recombinant and DNA Vaccines

Bacterial Vaccines

Suspensions of attenuated or killed bacteria, or their antigenic derivatives administered to induce an immune response for the prevention or treatment of bacterial disease 1-Capsular polysaccharide vaccines 2-Toxoid vaccines 3-Purified protein vaccines 4-Live attenuated bacterial vaccines 5-Killed bacterial vaccines

Vaccine Preventable Bacterial Diseases

Diphtheria Pertussis (Whooping Cough) Tetanus (Lockjaw) Pneumococcal disease Hib disease Meningococcal meningitis Typhoid Cholera Anthrax Plague

DTP vaccine against Diphtheria (Corynebacterium diphtheriae) Tetanus (Clostridium tetani) and Pertusis (Bordetella pertussis) Hib against meningitis caused by
Haemophilus influenzae

Meningococcal Vaccine against bacterial meningitis caused by Neisseria meningitidis BCG vaccine against pulmonary TB caused by Mycobacterium tuberculosis

Viral Vaccines

The development of antiviral vaccines is highly dependent upon the infection cycle of the viral pathogen itself.

Viruses that have an extracellular, viremic stage in the infection cycle are accessible to soluble humoral components are susceptible to antibodies.
Viruses that are highly cell associated, either through their ability to transport directly from one infected cell to an adjacent susceptible host cell, or have a cell-associated viremic stage, are not accessible to humoral components require direct recognition of infected cells implicates T cell responses. There are many different methods that can be used to vaccinate susceptible individuals live attenuated viruses, inactivated or killed viruses, virus-like particles, individual viral components, recombinant virus, pseudo virus, replicon each approach has its advantages and disadvantages Immunization can still result in immune escape variants.

Live attenuated vaccines:

Advantages: -The attenuated viruses replicate to some extent in the host -The attenuated viruses have a reduced capacity to spread from the site of replication -The attenuated viruses cause mild or in apparent disease

Disadvantages:
-Virus shedding and infection of unvaccinated individuals -Arisal of revertants due to compensatory mutations

Delivery of live attenuated viruses: Injection (e.g. measles-mumps-rubella vaccine) Oral (e.g. poliovirus, rotavirus, adenovirus vaccines) Nasal spray (respiratory viruses)

Recombinant DNA approaches to attenuation

Inactivated (killed) Virus Vaccines

Chemical inactivation: formalin - traditionally used; now being supplanted by: b-propiolactone, ethylenimines nonionic detergent-disruption Advantages: non-infectious relatively uncomplicated and inexpensive to produce killed virus more easily stored than live-virus vaccines Disadvantages: Injection of large amounts necessary to elicit antibody response Vaccine must be injected (no oral delivery) Multiple rounds of immunization required Vaccination does not result in complete immunity

Polysaccharide vaccines
Many bacteria are surrounded by a polysaccharide capsule- provides the antigens against which antibodies can act & protects the main bacterial cell from the bodies defense systems It is relatively easy to create polysaccharide vaccines against the molecules in the capsule; but these molecules are often small, and not very immunogenic. As a consequence they:

tend not to be effective in infants and young children (under 18-24 months) induce only short-term immunity - there is a slow immune response, with antibody levels rising slowly, with no immune memory. (The lack of immune memory means that on subsequent challenge there is no rapid response - it is as if the person being challenged had not encountered the antigens before.)

Frequent re-vaccination with any plain polysaccharide vaccine is generally avoided because of a poorlyunderstood phenomenon called immune tolerance which occurs with polysaccharide vaccines with each successive dose of a vaccine, there is a poorer immune response to it. In contrast to conjugate vaccines, polysaccharide vaccines induce antibody production, but do not induce a T-cell response. this means that they: -Do not induce immune memory; indeed, there is some evidence that some of them induce immune tolerance, a phenomenon whereby subsequent doses of vaccine induce poorer antibody response. -May not prevent colonization, e.g. of the nasopharynx by meningococci. This means that, while they provide personal protection, they may not provide herd immunity - a person can still be colonized (infected but not ill), and pass a potentially pathogenic bug on to somebody else.

Because they are relatively simple to produce, they are also relatively cheap and uncomplicated. For these reasons they are not generally suitable for universal use. Examples of polysaccharide vaccines which are, or have recently been used, include vaccines against: Meningococcal disease caused by Neisseria meningitidis Pneumococcal vaccine

Recombinant Vaccines
Recombinant vaccines are those in which genes for desired antigens are inserted into a vector, usually a virus, that has a very low virulence.

The vector expressing the antigen may be used as the vaccine, or the antigen may be purified and injected as a subunit vaccine. The only recombinant vaccine currently in use in humans is the Hepatitis B Virus (HBV) vaccine, which is a recombinant subunit vaccine Hepatitis B surface antigen is produced from a gene transfected into yeast cells and purified for injection as a subunit vaccine. This is much safer than using attenuated HBV, which could cause lethal hepatitis or liver cancer if it reverted to its virulent phenotype.

Another recombinant vaccine that has been successfully trialed for human use is the recombinant influenza vaccine, although it has not yet been produced on a commercial basis.