Microbiology Final-Vaccination lecutre
ODU PA Program: Professor Powell
Terms in this set (35)
The development of antibodies in response to antigenic stimulation.
Transferred protection through preformed antibodies produced by another individual.
-Longer duration of protection
Preformed antibodies (anti-tetanus serum):
-Shorter duration of protection
Disadvantages: no long term protection. serum sickness, risk of infection (Hepatitis or HIV), graft vs. host disease (cell graft only)
What are some natural examples of passive immunity?
-placental transfer of IgG
-Colostral transfer of IgA
What are some artificial examples of passive immunity?
-anitbodies or immunoglobulins
Describe the timeline of newborn and maternal immunity
-Maternal IgG peaks at birth then decreases
-newborn IgG and IgA begin at birth
-newborn IgM begins 3 months before birth
-A process of induction of immunity to a pathogen by deliberate injection of a weakened, modified or related form of the pathogen which is no longer pathogenic.
-One of the two most important contributions to public health in last 100 years.
-Some infectious diseases have been eradicated as result of vaccination.
-Principle of vaccination was established by Edward Jenner who used a cow virus, vaccinia to provide protection to humans against smallpox.
_____ antibodies are capable of binding to and neutralizing the smallpox virus.
Cowpox. This is the principle behind the smallpox vaccine.
Live, attenuated vaccines
Contain a version of the living microbe that has been weakened in the lab so it can't cause disease.
-closest thing to a natural infection (evokes local and systemic response)
-Induce robust immune responses
-Strong cellular responses (CD4 and CD8)
-Strong antibody responses (long-lived memory B cells)
-often confer lifelong immunity with only one or two doses
-can be given mucosal route
What are some disadvantages of a live, attenuated vaccine?
-Possibility of reversion to a virulent form, and contamination
-Contraindications in very young/old, people with damaged or weakened immune systems (chemotherapy patients, or HIV)
-Must be refrigerated...shipping/storage complications in developing countries. Can become inactivated in certain climates
-can cause disease in an immunocompromised host
Are live, attenuated vaccines easy to create?
Relatively easy to create (for certain) viruses due to small number of genes. It is easier to control their characteristics.
In live attenuated viruses, how do scientists "weaken" the virus?
-Viruses are attenuated in cells in which they do not reproduce very well. This hostile environment takes the "fight" out of viruses.
-When they evolve to adapt to the new environment, they become weaker with respect to their natural host, human beings.
Live, attenuated vaccines are more difficult to create for bacteria than viruses. Why?
-Bacteria have thousands of genes and thus are much harder to control
-recombinant DNA technology to remove several key genes in various bacteria is one approach. Vibrio cholerae is a live cholera vaccine and has not been licensed in the United States
What are some examples of live attenuated vaccines?
Vaccines against measles, mumps, and chickenpox, for example, are made by this method.
-flu shot (injection) of trivalent (three strains; usually A/H1N1, A/H3N2, and B) inactivated (killed) vaccine
-nasal spray (mist) of live attenuated influenza vaccine
How are viruses inactivated to create inactivated vaccines?
What are the advantages of inactivated vaccines?
-More stable and safer than live vaccines
-Microbes can't mutate back to their disease-causing state (revert and multiply)
-Don't require refrigeration and can be easily stored and transported in a freeze-dried form. This makes them accessible to people in developing countries.
What are the disadvantages of inactivated vaccines?
-Stimulate a weaker immune system response than do live vaccines, especially weak CMI response
-Usually takes several additional doses, or booster shots, to maintain a person's immunity.
-Unnatural route (injection)
-High Ag concentration needed
Instead of the entire microbe, subunit vaccines include only the antigens that best stimulate the immune system with an immunodominant epitope.
Chances of adverse reactions to the vaccine are lower because there are no live microbes and less microbial particles.
Subunit vaccines can contain anywhere from 1 to 20 or more antigens. Identifying which antigens best stimulate the immune system is a tricky, time-consuming process.
Subunit vaccines are formed in which two ways?
1. Microbes can be broken down into multiple antigenic components
2. Antigen molecules from the microbe can be manufactured using recombinant DNA technology.
Vaccines produced this way are called "recombinant subunit vaccines." An ex. is hepatitis B virus.
For bacteria that secrete toxins, or harmful chemicals, a toxoid vaccine might be the answer.
Used when a bacterial toxin is the main cause of illness. Toxins can be inactivated by treating them with formalin, a solution of formaldehyde and sterilized water. "Detoxified" toxins, called toxoids, are safe for use in vaccines.
Vaccines against diphtheria and tetanus are examples of toxoid vaccines
the ability to induce a humoral and/or cell-mediated immune response
the ability to combine specifically with Ab and/or cell-surface Ig/TCR
any agent capable of binding specifically to components of the immune response
any agent capable of inducing an immune response
**All immunogens are antigens, but not all Ags are immunogens
-Encapsulated bacteria may be more difficult for the immune system to detect.
-Polysaccharides (the outer coating of sugar molecules) can help such bacteria evade immune detection.
-A conjugate vaccine links antigens or toxoids from a microbe to the outer polysaccharides which helps the immature immune system react to polysaccharide coatings and defend against the disease-causing bacterium
Example: the vaccine that protects against Haemophilus influenzae type B (Hib) is a conjugate vaccine
Once the genes from a microbe have been analyzed, scientists could attempt to create a DNA vaccine against it. Still in the experimental stages, these vaccines show great promise, and several types are being tested in humans.
DNA vaccines use the genes that code for the immunodominant epitopes and antigens that confer pathogenicity and can inject the DNA directly. DNA is taken up by cells (usually DCs). DNA instructs those cells to make antigenic molecules. Cells will either secrete or display Ag on their surface and a specific immune response is induced against the antigen.
The body's own cells become "vaccine-making factories" creating the antigens necessary to stimulate the immune system.
Vaccines for infectious diseases
...balance the importance of antibody and CD8 T cell responses with the mode of protection and side effects of inflammation.
*Safety is a major concern that prevents the use of most adjuvants and limits the use of certain types of vaccines, such as attenuated microbes
What are the major limitations of cancer vaccines?
Major limitations involve the identification of robust antigens the elicit a strong, high affinity T cell response. Other barriers include the problem of chemotherapy induced immunosuppression and mutational escape of immune recognition by the tumors.
Recombinant vector vaccines
These use an attenuated virus or bacterium to introduce microbial DNA to cells of the body. Attenuated bacteria also can be used as vectors
Inserted genetic material causes the bacteria to display the antigens of other microbes on its surface
the harmless bacterium mimics a harmful microbe, provoking an immune response.
Researchers are working on both bacterial and viral-based recombinant vector vaccines for HIV, rabies, and measles.
Immunologic Adjuvants--what are they and what do they do?
Substance when mixed with an immunogen enhances the immune response.
-Prolongs antigen persistence leading to slower release of antigen at the injection site
-Enhances co-stimulatory signals: increased expression of MHC & B7 molecules and secretion of cytokines leads to increased antigen-presenting ability and maximal activation of TH cells
-Induces germinal center formation
-Stimulates lymphocyte proliferation
What are example of immunologic adjuvants?
Animal: complete Freund'sadjuvant (CFA, oil-in water emulsion)
Human: Alum (aluminum hydroxide) only adjuvant used for human vaccines in the US
Modern Adjuvants: TLR agonists (CpG), Cytokines (GM-CSF, IL2)
What are the general steps of vaccine development?
1. Laboratory tests
2. Animal tests
3. Human clinical trials
a. Phase I
b. Phase II
c. Phase III
4. Limited sample
5. Restricted sample
What is herd immunity?
Vaccination programs rely on herd immunity
ensure optimal protection of a community from communicable disease transmission.
The more people that are vaccinated, the fewer susceptible individuals will be exposed and the less likely person-to-person transmission will occur or be sustained.
*In most cases vaccination of 95% of a population is considered optimal.
What are some problems with herd immunity?
-Under vaccination in children