Vaccine - Introduction, Live Attenuated, Inactivated, Live Recombinant, Virion Subunit Vaccine
Introduction to Vaccine
Vaccines are materials/substances that when introduced into the body induce an immunological response against the virus involved. Both humoral and cell-mediated immunity may be induced.
The purpose of a vaccine is to induce an immune response and establish long-term immunological memory which protects if the virus ever invades the body.
The two criteria of viruses are
Viruses antigen must be similar/identical to that of the wild type so that immunological response against vaccine virus provides protection against wild type
Vaccine virulence must be attended to by suitable procedures
Vaccine Types | Examples |
|---|---|
Live attenuated virus vaccine | Sabin – Polio |
Inactivated virus vaccine | Salk – Polio |
Virion subunit vaccine | Influenza (Haemagglution and Neurammide) |
Live recombinant virus vaccine | Rabies (for wildlife) |
Virus-like particle vaccine | Hepatitis B |
DNA particle | SARS coronavirus (experimental) |
Live attenuated virus vaccine
Live attenuated virus vaccine contains a mutated strain of virus derived from a wild-type virulent strain. This type of vaccine is usually obtained by repeated culturing. A small dose is administered.
To produce an immune response, a live attenuated virus must replicate in a vaccinated person. Live attenuated vaccines replicate but do not cause disease such as with wild form. If/When live attenuated vaccine does cause ‘disease’ they are much milder than the wild strain.
Development approaches
Hit and miss
It is done by the repeated passage of wild-type viruses in cells unrelated to the normal host.
Eg: 3 serotypes of poliovirus derived from wide-type strains are attenuated by a passage in monkey kidney cell lines resulting in loss of ability to infect neurons
Other attenuated vaccines by this approach include mumps, measles, rubella, yellow fever, canine parvovirus, and canine distemper.
Cold-adapted virus strains
These vaccines are derived by incubating virus-infected cell cultures at a temperature below the optimum for viral replication.
Eg: Influenza, the respiratory syncytial virus vaccine
Reassortments
Developed with some genes derived from the human virus and some genes from an animal virus.
Eg: Rotavirus vaccine
Reverse genetics
Developed by engineering mutations into virus genome that attenuated vaccine.
Disadvantages
It may cause severe/fatal reactions as a result of uncontrolled replication of the vaccine virus in an immunodeficient person.
During virus replication, nucleotide substitution may occur resulting in reversion to virulence.
Inactivated virus vaccine
This type of vaccine is prepared by mass-producing virulent viruses and then inactivating them ineffectively usually by treatment with a chemical such as formaldehyde.
The inactivation process completely inactivates the virus bit and leaves antigens unchanged so that they can still stimulate a protective immune response. They are not alive, and cannot replicate so does not cause disease even in an immunodeficient person.
Eg: Salk Vaccine is made by treatment of virion in formalin (formaldehyde solution) at 37°C for 10 days. Other eg include the Influenza vaccine, Hepatitis A vaccine, Foot and mother disease vaccine.
They always require multiple doses:
The 1st dose: does not produce protective immunity but “primes” the immune system
2nd/3rd dose: protective immune response develops
Mostly humoral immunity is involved with little or no antibody-mediated Humoral Immunity (AMI). Antibody titer diminishes with time so booster doses must be given to increase antibody titer.
Virulent strains used for production procedures and 100% infectivity, and virulence must be destroyed.
Virion subunit vaccine
Virion subunit vaccine contains purified components of virions. It induces poor immune response so two doses are necessary to provide adequate immunity.
Eg: The influenza vaccine contains Haemagglutination (H) and Neuraminidase (N) surface glycoprotein.
Steps
Influenza virion is inactivated by formaldehyde or β-propiolactone
Virion envelope removed with detergent (eg: Triton ᵞ-100)
Glycoprotein removed – H ‘cartwheels’ and N ‘rosettes’ are aggregated
These structures are purified by centrifugation in a sucrose gradient
Materials from 3 influenza virus strains are combined
The vaccine is formed/produced
Live recombinant virus vaccine/recombinant vaccine
They are produced by genetic engineering technology. Eg: vaccines for HBV, HPV, Influenza virus
The desired segment of the viral gene is inserted into a modified yeast cell or virus. The modified yeast cell/virus produces pure HBV surface Ag, HPV capsid protein, and Influenza haemagglutination. Thus, the respective vaccine is produced.