Vaccines Flashcards
variolation:
term for delivery of initial smallpox vaccine either intranasally or intradermally (scratch on the arm)
vaccinia:
another name for the virus used to vaccinate against smallpox (vaccinia virus)
vaccination:
any deliberate immunization that induces immune responses (if successful, protective acquired immune responses);
the word vaccination was derived for the latin word for cow (vaccus) because the first successful vaccine used the cowpox virus to immunize against smallpox
immunization:
the deliberate prevocation of an acquired immune response by introducing antigen into the body
killed or inactivated vaccines:
any vaccine that employs killed pathogens as the antigen; the pathogens can be killed either by
chemical treatment, heat, or irradiation
attenuated vaccines:
any vaccine protocol that employs “weakened” pathogens as the immunogen;
pathogens can be weakened by several methods, and the result is that the attenuated pathogen’s ability to cause disease is either weakened or destroyed
subunit vaccine:
vaccines that employ only part of the pathogen as the vaccine immunogen
toxoid:
an inactivated toxin used as a vaccine immunogen whose toxic activity has been destroyed (usually by chemical treatment)
How was the first vaccination done?
a small amount of this material was administered to healthy people thru variolation
How did the cowpox vaccine from Jenner work against smallpox?
shared many antigens;
immune responses to cowpox were cross-reactive with smallpox virus and these responses were protective
What type of vaccine is Diphtheria-tetanus pertussis (DTP/DTaP)?
killed subunits/toxoids
What type of vaccine is inactivated polio vaccine?
whole killed virions
What type of vaccine is Measles/mumps/rubella (MMR)?
live attenuated viruses
What type of vaccine is pneumococcal conjugate?
heptavalent / diptheria
What type of vaccine is Haemophilus B conjugate (HBC)?
Diptheria rotein conjugate
What type of vaccine is hepatitis B?
subunit
What type of vaccine is varicella (chickenpox virus)?
live attenuated
What type of vaccine is rotavirus?
live attenuated
What type of vaccine is influenza?
killed or live attenuated
What type of vaccine is meningococcus C?
conjugated capsule subunit
What type of vaccine is human papillomavirus?
Gardasil: virus-like particles
the most widely used whole live bacterial vaccine is what?
BCG vaccine
How are subunit vaccines made and what bacteria are responsible for this?
bacterial toxins that have been inactivated (toxoids) can also be used as vaccine immunogens
toxins can be purified and deactivated by treating them with formalin and used as a subunit vaccine
- Corynebacterium diphtheriae
- Clostridium tetani
both produce a toxin that causes disease
DTP combination vaccine is a vaccine that is routinely administered to children in the U.S. What is the combination?
diphtheria and tetanus toxoids have been combined with a killed preparation of Bordetella pertussis
Viral vaccines use what forms of the virus as the vaccine immunogen?
either 1) killed, 2) subunit, or 3) attenuated forms of the virus as the vaccine immunogens
What do killed virus vaccines consist of? what are they used for?
consist of virus particles that have been killed by chemical treatment or irradiation
currently used vaccine for influenza and the Salk polio vaccine
What is an attenuated virus? How does it work? How commonly is it used?
an attenuated virus particle is one whose ability to cause disease has been reduced or eliminated, but it is still able to replicate in the host so that it mimics a real infection
most anti-viral vaccines are live-attenuated vaccines, including the measles, mumps, Sabin polio, and yellow fever vaccines
Production of strong immune responses to an antigen almost always requires that the antigen be mixed with an adjuvant prior to administration. What is an adjuvant?
is any substance that enhances the immunogenicity of an antigen.
An adjuvant can be added to an immunogen prior to immunization (vaccination)
What are the 3 reasons adjuvants promote immune response?
1) increase the length of exposure of the immune system to an antigen by releasing the antigen slowly over an extended period of time (termed depot formation).
2) often cause inflammation, thus promoting uptake of the antigen by macrophages
3) specifically elicit mucosal immune responses (secretory IgA, or sIgA)
How do adjuvants slowly release antigen to increase immune response?
adjuvants turn a soluble protein antigen into a particulate antigen which is more readily ingested by antigen-presenting cells
What is an example of an adjuvant that causes inflammation and depot formation?
Freund’s adjuvant
How does Frued’s adjuvant increase the immune response?
this adjuvant is composed of mineral oil (depot formation) and mycobacterial cell wall components (a source of PAMPs for induction of inflammation).
When an antigen is emulsified in this adjuvant, its immunogenicity can be increased many fold.
What are examples of adjuvants that specifically elicit mucosal immune responses?
cholera toxin, tetanus toxin, E. coli lymphotoxin
What is a liposome?
a highly stable closed vesicle formed by a single bilayer of phospholipids
How do liposomes promote immune responsiveness?
liposomes enable delivery of immunogens into the cytoplasm of host cells
What type of vaccines are liposomes generally used with? How does this improve immune response?
typically used with subunit vaccines and are used to deliver immunogen into the cytoplasm of antigen-presenting cells;
this promotes processing and presentation of the immunogen through the MHC class I processing and presentation pathway
What are the 4 methods of making attenuated viruses?
- grow a human viral pathogen in cells of non-human origin
- mutation of viruses using recombinant DNA
- Recombinant techniques can also be used to clone a gene(s) from a pathogen into plasmid DNA, and the plasmid can be
administered as a vaccine - can sometimes be isolated from an infected individual
How is an attenuating virus grown on a non-human origin chosen to become the virus of choice within the vaccine?
- as the virus replicates in the non-human cells, mutant viruses that grow better/faster in these cells are selected for
- a virus that has been adapted for growth in non-human cells is typically attenuated in its ability to replicate in human cells
What is the premise of using recombinanat DNA for attenuating viral vaccines?
the virulence gene(s) of a particular virus can be deleted or mutated, rendering the virus unable to cause disease
For recombinant DNA to be effective, What is the critical point?
a virulence gene that does not play a role in the ability of the virus to infect cells or replicate within host cells must be identified
How can recombinant DNA be used to prepare a subunit vaccine
used to clone viral or bacterial genes, and to express these genes in non-pathogenic bacteria (or virus) to generate protein for a subunit vaccine
What other 2 ways could recombinant DNA be used to promote immune responsiveness and increase a vaccines ability to recognize a different pathogen?
recombinant techniques can also be used to insert genes from a pathogen into a currently used bacterial or viral vaccine strain; this recombinant vaccine strain could then be used as a vaccine against a different pathogen
it is also possible to insert genes encoding proteins that have adjuvant properties into a vaccine strain; the adjuvant could then promote immune responsiveness to the vaccine
Recombinant techniques can also be used to clone a gene(s) from a pathogen into plasmid DNA, and the plasmid can be administered as a vaccine. How does this work and how are they administered?
DNA vaccines are usually administered either intramuscularly, or intranasally
the DNA is taken up by cells and the encoded recombinant protein is expressed by the host cell
Describe how attenuated viruses can sometimes be isolated from an infected individual
sometimes during replication, viruses with natural- occurring mutations that increase their ability to replicate, but reduce their pathogenicity become the predominant strain of virus growing in that host
Why are Attenuated vaccines are not always 100% safe?
because of their similarity to the pathogen, an attenuated vaccine can revert to becoming a pathogenic strain
What is an example of recombinant attenuated viral vaccine that is efficacious?
rotovirus vaccines
How is a rotovirus similar to the influenza virus?
1) it has a segmented genome (11 dsRNA molecules),
2) antibody responses directed against surface proteins of the virus are protective via neutralization
What gives rise to the distinct serotypes of the rotovirus?
the two coat proteins that are important immunological targets are the VP4 and VP7 proteins;
these envelope **glycoproteins are variable due to frequent mutation, **
Why is the reassortment of genome segments in cells infected with two distinct rotovirus serotypes important?
can give rise to immunologically distinct viruses
What is the rotarix vaccine?
consists of an attenuated human virus with common VP4 and VP7 variants
What is the RotaTeq vaccine?
consists of a mixture of 5 cattle rotovirus strains that do not cause disease in humans;
each has been engineered to express a different common VD4 and VD7 glycoprotein of the 5 most virulent human strains
CYTOKINES CAN BE USED TO MODULATE IMMUNE RESPONSE TO PATHOGENS AND VACCINE IMMUNOGENS in what 4 ways?
- helps to shape developing acquired immune responses due to the different roles the two types of effector CD4 T cells perform in the development of acquired immunity
- administered therapeutically to alter the outcome of infection
- Removal or inhibition of cytokines can also alter outcome of infection
- shown to have powerful adjuvant properties when co- administered with antigen as a vaccine component
Describe the difference of the effector CD4 T cells in the development of acquired immunity
the cytokines produced by TH1 cells promote the development of immune responses that are effective for clearance of intracellular pathogens; these cytokines also inhibit the development of TH2 cells
the cytokines produced by TH2 effector cells promote the development of immune responses that are best for clearance of extracellular pathogens; these cytokines also inhibit the development of TH1 effector cells
What cytokines produce a Th1 response?
IL-12, TNF-a
What cytokines produce a Th2 response?
IL-4, IL-5, IL-6
Describe how removal or inhibition of cytokines can also alter outcome of infection.
If an intracellular parasite infection occurs, and the host is given anti-IL-4-Abs (IL-4 promotes Th2) then the host will be able to form an effective Th1 response because the cytokine was effectively inhibited
How should a toxoid be delivered?
extracellularly
