L20: Vaccines

Question 1

Passive immunity

Answer 1

when the antibodies produced by one organism are transferred to and protect another.

Question 2

Sources of passive immunity

Answer 2

1) mothers antibodies across placenta
2) maternal antibodies in colostrum/breast milk
3) serum from other organism introduced into body

Question 3

Clinical scenarios where antibody therapy (passive immunity) is useful

Answer 3

a. Patient is immunodeficient or otherwise vulnerable (has leukemia and gets exposed)
b. Patient is exposed and could experience complications before traditional treatments are effective (tetanus exposure in someone with up-to-date vaccine, anthrax infection to remove the toxin).
c. Individual bitten by venomous snake or insect – horse antibodies tie it up

Question 4

Problems with passive immune therapy

Answer 4

a. Short term and no memory developed to pathogen, toxin or venom.
b. Serum sickness – may develop antibodies to the foreign antibodies: type III hypersensitivity.
c. Engineered monoclonal “humanized” antibodies make this less of a problem.

Question 5

What’s considered Active immunity?

Answer 5

Vaccines

Question 6

Who is responsible for the anti-vacc movement and what did he do?

Answer 6

In 1998, Andrew Wakefield reported a correlation between symptoms and autism in 12 children and proposed a correlation improved vaccination the rise of autism diagnoses in California, suggesting that thiomersal, a mercury-based preservative,
was the cause.

Question 7

Methods for making live attenuated vaccines

Answer 7

a. Select for growth in culture medium, e.g. Mycobacterium bovis grown on medium with increasing amounts of bile for TB vaccine.
b. Grow virus on another species and they become better at infecting that one than they are at infecting us: Sabine in monkey kidney epithelial cells, rubella on duck embryo cells.
c. Select for growth under non-physiological conditions. FluMist selected at cold temperatures, and can only infect the cooler parts of the upper respiratory tract.

Question 8

advantages of live attenuated vaccines

Answer 8

a. Mount a full immune response, including class switching and memory cell production and activation of TC cells.
b. Need for fewer (or no) boosters – Sabin oral vaccine requires three exposures because it has three different viruses, and each time only one mounts enough of an infection to produce immunity, but once you’ve got it, you’ve got it.

Question 9

Disadvantages of live attenuated vaccines

Answer 9

a. They may revert to virulent form which then gets passed on.
b. They may produce a serious infection in an immune compromised recipient, even when fully attenuated.
c. They may be contaminated with other viruses

Question 10

“Killed” Vaccines

Answer 10

from dead bacteria or completely inactivated viruses.

Question 11

Advantages of killed vaccines

Answer 11

Once they’re dead, they’re dead. They’re not going to infect the immune compromised. - Salk polio and current pertussis.

Question 12

Disadvantages of killed vaccines

Answer 12

a. Must be careful not to denature the proteins needed to provide B cells with epitopes.
b. mainly humoral response
c. need repeated boosters
d. some viruses may get through “alive”
e. can still get bad reactions to multiple agents in whole bacteria (pertussis)

Question 13

Examples of killed vaccines

Answer 13

a. injectable flu (both seasonal and H1N1)
b. hepatitis A
c. cholera

Question 14

Vaccines from Specific Macromolecules

Answer 14

purifying macromolecules is a way to get
around the problems of injecting uncharacterized mixtures of molecules into people
    -bacterial lipids and LPS
    -bacterial toxoids
    -pathogen proteins

Question 15

vaccines from bacterial lipids and LPS

Answer 15

remember that strep is virulent because its
capsule presents neutrophils from killing it before the body can tag it with antibodies. Well, you can vaccinate with just the capsule.

Question 16

vaccines from bacterial toxoids

Answer 16

A toxoid is a toxin that has been inactivated enough to be safe, yet will still promote and immune response that will knock out the real toxin used for diphtheria and tetanus toxins, but you have to be careful to inactivate without denaturing.

Question 17

vaccines from pathogen proteins

Answer 17

Engineer bacteria, yeast or mammalian tissue culture cells
with the gene for a pathogenic protein. You can then harvest the protein in quantity and inject it as a vaccine. Such vaccines require adjuvants, as the proteins by itself (unlike bacterial lipids and polysaccharides) will not provide a danger signal.

Question 18

Adjuvants

Answer 18

a substance that enhances the body’s immune response to an antigen.

Question 19

conjugate vaccines

Answer 19

is created by covalently attaching a poor (polysaccharide) antigen to a carrier protein (preferably from the same microorganism), thereby conferring the immunological attributes of the carrier to the attached antigen.

Question 20

example of conjugate vaccine

Answer 20

Hib vaccine to Haemophilus influenzai has polysaccharideconjugated to tetanus toxoid.

Question 21

SMAA (solid matrix antibody antigen complex)

Answer 21

You can hook both T- and B-cell epitopes to antibodies held on a solid matrix.

Question 22

ISCOM (Immunostimulating complex)

Answer 22

activates a TC cell (and possibly TH during cross presentation) – placing the antigens at the center of a detergent complexed with Quil A, a glycoside that can interact with membrane components. This will actually feed the antigen directly into the cell where they can be hydrolyzed in a proteasome and fed into the MHC I complex

Question 23

DNA vaccines

Answer 23

is a technique for protecting an animal against disease by injecting it with genetically engineered DNA so cells directly produce an antigen, resulting in a protective immunological response.

Question 24

Method of DNA vaccines

Answer 24

a. Grow up a batch of plasmid DNA coding for pathogenic antigens.
b. Inject the DNA into the muscle of the recipient.
c. The DNA is taken up and expressed by the muscles, producing a batch of foreign antigen.
d. The DNA may also be taken up by local dendritic cells, which may in fact do the actual stimulating.
e. The antigens stimulate both humoral and cell-mediated immunity, activating both T and B memory cells.

Question 25

Advantages of DNA vaccines

Answer 25

a. need not refrigerate
b. can engineer the same plasmid against more than one pathogen
c. can deliver on particle with gene gun ( no messy needles)
d. can engineer the gene with unmethylated CpG sequences, which will serve as adjuvants, activating TLR9

Question 26

Disadvantages of DNA vaccines

Answer 26

a. only works for protein antigens
b. Must be i.m.- can’t use with oral or nasal spray versions.
c. Early version didn’t work very well in humans (great for mice and chickens)

Question 27

Recombinant vector vaccines

Answer 27

This is a way of using existing vaccines to confer

immunity on a new and/or especially virulent pathogen.