Lec 21 Vaccines

Question 1

What is immunotherapy?

Answer 1

the application of any pharmaceutical or biological agent able to modulate immune responses to treat a disease

Question 2

What is pharmacodynamics

Answer 2

the study of how a medication (biological or chemical) affects the body. The changes caused by the medication on the body.

Question 3

What is pharmacokinetics

Answer 3

• absorption: how the drug enters the body
• distribution: how the drugs spreads through the body
• metabolism: how the drug chemically alters the body
• excretion: how the drug or its metabolites are removed from the body

Question 4

Examples of immunotherapeutic drugs

Answer 4

corticosteroids
cyclophosphamide
cyclosporin A, tacrolimus

Question 5

how do corticosteroids act?

Answer 5

inhibit inflammation, inhibit many targets including cytokine production by macrophages

Question 6

how does cyclophosphamide act?

Answer 6

inhibit proliferation of lymphocytes by interfering with DNA synthesis (the cells that replicate the most)

Question 7

how does cyclosporin A/tacrolimus act?

Answer 7

inhibit calcineurin dependent activation of NFAT; block IL2 production and proliferation by T cells

Question 8

Omab antibodies

Answer 8

fully mouse(not good long term, effect is reduced)

Question 9

Ximab antibodies

Answer 9

chimeric: mouse variable region, human constant region

Question 10

Zumab antibodies

Answer 10

Humanized
V(D)J mouse regions

Question 11

Umab antibodies

Answer 11

fully human

Question 12

What is a vaccine?

Answer 12

any formulation able to elicit antigen specific protective immunological memory

Question 13

with ______ after 1st exposure, the 2nd exposure can elicit a strong _________. Best response is by ______

Answer 13

memory;
adaptive immune response;
live attenuated vaccine

Question 14

Difference in response in vaccination vs unvaccinated person

Answer 14

controls pathogen faster, increased T cell and antibody respoonse, dampens infection, pathogen cleared quickly, low level of pathogen load

Question 15

What are the active principles of a vaccine?

Answer 15

specific components responsible for its biological effects (B/T cell epitope that induces memory)

Question 16

Components of a vaccine

Answer 16

• delivery vehicle (antigen presentation)
• adjuvant (signals danger) starts innate response and shapes adaptive mechanisms
• active principle (immune epitope

Question 17

Classic principle of vaccine induced immunity

Answer 17

protection mediated by exposure of an immunogenic agent to a host followed by the natural immune responses

Question 18

What determines pharmacokinetics and pharmacodynamics of a vaccine?

Answer 18

adjuvant
packaging
tools to get genetic material inside the cell

Question 19

Live vaccines

Answer 19

formulations where antigens are encoded by replicating genetic material (attenuated)
antigens are synthesized in the host

Question 20

Inactive vaccines

Answer 20

formulations where the protein or polysaccharide agents are directly injected into the host or non replicating genetic material

Question 21

Live vaccines are the whole organism and may be

Answer 21

• host attenuated (mutant)
• recombinant mutant

Question 22

Inactive vaccines can be a subunit and may be

Answer 22

• purified fraction from the organism
• recombinant agent

Question 23

inactive vaccines can be the whole organism and may be

Answer 23

• structural antigens (viral particles - supernatant)
• structural and nonstructural antigens (cell extract)

Question 24

Live and inactive vaccines are presented on ____ inducing, ___ response

Answer 24

MHC II
CD4+ response

Question 25

Live and genetic vaccines are presented on ____, inducing ___ response

Answer 25

MHC I; CTL

Question 26

Basic mechanisms of vaccine mediated protection

Answer 26

B cell (antibodies) - neutralization and opsonization
T cell - cytokine secretion and cytolytic activities

Question 27

live attenuated viruses have

Answer 27

infectious agent
natural adjuvant (built in ways to activate PRRs), strong innate inflammatory responses
strong induction of B and T cell response (longer memory)

Question 28

Classic method of viral attenuation

Answer 28

grow in monkey (other animal) cells so it acquires mutations where it no longer grows well in human cells

Question 29

Characteristics of inactive vaccine (proteins)

Answer 29

local antigen deposit and distribution to regional lymph nodes,
requires additional adjuvant;
mainly induce antibody response (weak CD8)

Question 30

Without CD4+ help, a B cell response will find it hard to ______

Answer 30

class switch and induce memory cells

Question 31

Modern vaccine design principle

Answer 31

induce modulation of immunological mechanisms to target specific cognitive and effector responses and to achieve immunity and reduce immune related toxicity. Easier preparation and greater stability

Question 32

How are nucleic acid based vaccines delivered?

Answer 32

• lipid based
• polymer based
• peptide based (protamine - issue with DNA release)
• virus like replicon particle
• cationic nanoemulsion
• naked mRNAs
• DC based mRNA

Question 33

AAV LAMP/Gag vaccine

Answer 33

vector genome, viral vector construct, Rep/Cap construct packaged in AAV capsid

Question 34

Vaccines require high ____ and high _____

Answer 34

safety and efficacy

Question 35

features of effective vaccines

Answer 35

safe
protective
gives sustained protection
induces neutralizing antibodies
induces protective T cells
practical considerations (low cost, few side effects, stable, easy to administer)

Question 36

Herd immunity

Answer 36

enough people have immunity (natural or artificial) to stop the spread of the disease in the population

Question 37

How long do the mother’s antibodies last in the baby transferred via placenta?

Answer 37

18 months

Question 38

Immunological differences in neonates

Answer 38

immature lymphoid organ architecture
Limited secretion of IFN gamma by Th1 (limited CD8 response)
impaired TLR 3 and 9
Limited T cell independent responses
delayed maturation of dendritic cells (limited IL12, limited activation CD4+ cells, delayed and limited induction of GCs - low Ab responses)
Maternal antibodies - epitope specific and does not affect T cell priming
Immunize early and boost

Question 39

Immunological differences in elderly

Answer 39

thymic regression
impaired TCR-MHC
CD8 cellular senescence
deregulation of macrophage function