Lec 19 Viral Vaccinations Flashcards
Vaccines: Smallpox
VARIOLATION
The basic strategy consisted of two components: carefully monitored mass vaccination programmes to reach 80% of the population and a new approach to disease prevention — surveillance and containment.
1721 Lady Montaque: VARIOLATION (inoculation of patient with pus from a recovering smallpox victim)
1798 Jenner developed vaccination using cowpox inoculation to protect against smallpox
1885 Pasteur introduced air-dried rabbit spinal cord as a rabies vaccine
Vaccine Strategy
Produce protective immunity without endangering host
Immunogenic but avirulent vaccine needed
A balanced humoral and cell-mediated response desired
Long lasting protection, Few side effects, should not be worse than infection
Options:
Live wild type virus, Live Attenuated Virus, Inactivated Virus, Virus Subunit Vaccines, Chimeric Vaccines, DNA Vaccines
Live wild type Vaccines
Vaccina (Cowpox)
Use viruses from other species
LOW INFECTIVITY in humans but STILL MAINTAIN ANTIGENICITY to produce immune response
Vaccinia (cowpox) vaccine eradicated cold pox.
Live Attenuated viruses
Influenza A
Virus altered by SERIAL PASSAGES in tissue culture cells to lower virulence.
Can grow in Humans and induce immune response
Little disease
Very successful vaccines b/c VIRUS GROWS, Immunity can last 10 years to life
Cold adapted influenza A (Flumist)
Grown at lower temperature than body. Inhale the virus thru nasal path so it grows enough to alert immune response w/o causing systemic infection! Body temp won’t let it grow well.
Edmonston-B: measles vaccine was attenuated via reduced temperatures.
Advantages of Attenuated Vaccines
Agent is infectious, grows in host and induces complete immune response, both HUMORAL and CELL MEDIATED.
HUMORAL response is the PRODUCTION of SPECIFIC Ab that neutralizes virus to inhibit infection.
CELL MEDIATED response is a T-cell response leading to the lyses of cells growing virus.
A cell mediated response is required to completely eradicate virus infection.
Requires only a small amount of antigen
Immune response to a wide range of viral antigens
Typically doesn’t require booster shot
Closest response to natural infection giving high titer Ab and good cell mediated response
Typically produces a good memory response
Humoral and Cell-mediated immune response
Cell mediated: Cytotoxic T cells kill infected cells w/ foreign antigens.
Disadvantages of Attenuated Vaccines
Producing low virulent virus with antigenicity intact is tough! Some too virulent, some not protective, others caused hyper reactive immune response!
REVERSION an issue, vaccine virus activity is dead is heated (not cooled), will it cause disease (Polio) especially if immunocompromised
Unstable and require that a “cold chain” be maintained
developing countries issue
Expensive to produce
Host considerations (immune status)
CONTAMINATION
INACTIVATED VIRAL Vaccines
ADJUVANT
Virus is killed so no infection is possible, but process of inactivation leaves antigenicity intact. Break the viral components!
Because the virus is not replicating, high concentration (mg) of antigen is required and
an adjuvant must typically be added to vaccine
ADJUVANT a substance that enhances the immune response when added with antigens
Advantages of Inactivated Virus Vaccines
Humoral response seen, very small cell mediated response
Advantages of Inactivated Virus Vaccines
Safer for immune compromised
There should be no live virus, therefore no infection or danger of disease to individual or community due to reversion of attenuated virus
Humoral response seen, very small cell mediated response
Immune response to a wide range of viral antigens
MORE STABLE THAN LIVE VACCINE for third world use (don’t need to keep it refrigerated)
Disadvantages of Inactivated Vaccines
Disadvantages of Inactivated Vaccines
Require large amounts of Ag, therefore expensive to produce.
Must make lots of virus and then treat to kill with formaldehyde, organic solvents, detergents, or high temperature etc.
Requires adjuvant that can lead to side effects and typically favors a humoral response
Typically REQUIRES MULTIPLE INJECTIONS and fades with time requiring BOOSTER SHOTS
Subunit Vaccines
Hepatitis
In Subunit Vaccines
Produce virus and isolate proteins from it OR
Put proteins from other viruses into the vaccine
Key protective Ag is identified and molecular biology methods are used to produce Ag
Hepatitis B surface antigen, HPV vaccines
Host is never exposed to infectious agent so viral disease not an issue
Some cell mediated immune response, not as strong as live virus
Advantages of Subunit Vaccine
Advantages of Subunit Vaccine
SIMPLEST and LEAST EXPENSIVE vaccine to produce
Very stable vaccines
No direct virus contact and only exposure to target antigens less chance for side effects
Safe for immunocompromised people
HepB vaccine first licensed subunit vaccine
Disadvantages of Subunit Vaccines
Disadvantages of Subunit Vaccines
Require adjuvants, so increased chance of side effects
Humoral response poor and/or no cell mediated response
Difficulty in identifying target Ag
Best immunogen (protein that elicits immune response) may not be most effective vaccine
Require MULTIPLE INJECTIONS and periodic boosting
Chimeric Vaccines
Rotavirus vaccine
Chimeric Vaccines
Combination of live virus vaccine and subunit vaccine, vector virus is a known safe carrier (often pox) and subunits can be from multiple viruses
Can immunize against a number of viruses without being exposed to any of them
Advantages of Chimeric Vaccines
Advantages of Chimeric Vaccines
Can get a balanced response by using an infectious carrier virus
Immunize against multiple infectious agents or multiple serotypes of a single agent without exposure to pathogens
Will need multiple vectors or we limit usefulness of system as you develop an immune response to vector as well
