30- Scientific Basis of Vaccines

Question 1

what is a vaccine?

Answer 1

a biological substance derived from micro-organism material that, when administered, stimulates the immune system to provide a adaptive immune response with immunological memory that provides protection against future disease

Question 2

what make a good vaccine? - considerations for vaccine development

Answer 2

induces an appropriate response - cell-mediated, antibody-driven? - e.g. intracellular pathogens invade host cells, CD8+ T cell activation is preferred

long or short term protection? - e.g. travelling abroad, short-term vaccines may be sufficient

memory cells? what type - T or B cells?

should the immune response be systemic or localised - e.g. for respiratory infections, a localised response to mucosal surfaces with IgA is induced more with oral vaccines

Question 3

what are the three main reasons for vaccines?

Answer 3

protecting the individual - preventing disease or at least reducing severity

protecting the population - ensuring herd immunity, protect those that aren’t vaccinated

eradicating disease

Question 4

what is the vaccine paradox?

Answer 4

the more we vaccinate = disease rates decrease = less natural boosting = increases importance of vaccination uptake rates

Question 5

what is herd immunity?

Answer 5

indirect protection from an infectious disease through immunity in a threshold proportion of a population by vaccination or prior exposure

Question 6

describe the primary and secondary immune responses to a pathogen

Answer 6

primary response:
- innate immune activity occurs first
- takes 5-7 days for an antibody response
- 2 weeks for a full response with IgM to IgG switching, and forming memory T and B cells

secondary response:
- prior exposure means it takes less than 7 days for a full protective response

Question 7

list the general principles considered when making/ delivering vaccines?

Answer 7

inducing the correct type of response - antibodies, cell-mediated, cytotoxic T cells?

inducing a response in the right place - localised/ systemic?

long-term or short-term immunity? boosters? incubation time of pathogen?

age of vaccination

monotypic or polytypic pathogen

Question 8

what are the general principles considered when making and delivering vaccines?

Answer 8

inducing the correct type of response - e.g. antibody-driven for polio, cell-mediated for intracellular pathogens like TB

induce a response in the right place - e.g. injected vaccines for a more systemic response, oral vaccines better for respiratory infections and a localised mucosal IgA response

duration of protection - long-term for diseases like TB, short-term for going abroad

boosters, type of infection and its incubation time

age of vaccination - maternal IgA bodies from placental transfer and sIgA antibodies from breast milk offer protection to new-born, may interfere with vaccines

monotypic/ polytypic pathogens
- monotypic pathogens = surface antigens remain relatively the same, vaccine gives lifelong immunity along with herd immunity and reduced environmental presence - e.g. measles
- polytypic pathogens = surface antigens change and immunity is easily overcome through antigenic drift/ shift - e.g. influenzas, requires seasonal vaccines

Question 9

what is antigenic drift?

Answer 9

accumulation of small, gradual mutations in genes that code for virus surface proteins with time

Question 10

what is antigenic shift?

Answer 10

recombination of viral strains to produce a different subtype with a mixture of surface antigens from the original strains

Question 11

list the four types of vaccines

Answer 11

live attenuated organisms
killed/ inactivated whole organisms
subunit vaccines - individual components
vaccine adjuvants

Question 12

examples of live attenuated vaccines?

Answer 12

BCG for TB
MMR
yellow fever

Question 13

methods for generating a live attenuated vaccine?

Answer 13

there are three methods:

1. repeated serial culturing of a virus in non-human host until it loses its ability to cause disease
2. chemical exposure inducing mutagenesis in pathogens, then selecting strains with reduced virulence
3. genetic engineering to disrupt/ delete virulence genes and render bacteria unable to cause disease (knock-out virulence genes)

Question 14

advantages of a live attenuated vaccine?

Answer 14

induces a strong, long-lasting immune response, no need for a booster
- effective at producing CD8+ memory cells

Question 15

disadvantage of a live attenuated vaccine?

Answer 15

chance of reverting to virulence and causing vaccine-derived disease instead

requires refrigeration at cold temperatures, adds to the cost

Question 16

examples of killed/ inactivate whole organism vaccines?

Answer 16

pertussis
influenza
polio
cholera
HepA

Question 17

method for generating killed/ inactivated vaccines?

Answer 17

kill pathogen with heat or chemicals - e.g. formalin

Question 18

disadvantages of killed/ inactivated vaccines?

Answer 18

requires booster doses - sometimes the first dose doesn’t take, and second/third doses are needed

live attenuated vaccines only need a single dose as the live vaccine grows and continually presents antigen, continually stimualtes immune system

Question 19

advantages of killed/ inactivated vaccines?

Answer 19

following first dose and booster doses - ensures a robust immune response, increases with every dose

Question 20

components used for subunit vaccines?

Answer 20

proteins from surface antigens
toxoids
synthetic peptides
polysaccharides

Question 21

method for creating subunit toxoid vaccines?

Answer 21

bacterial toxins are isolated and inactivated with formaldehyde - produces a toxoid which maintains the same antigenic peptides, still immunogenic but not toxic

prevent tissue damage and disease, induces B cell antibody response

Question 22

method for creating subunit polysaccharide vaccines?

Answer 22

polysaccharides from bacterial capsules - often poor antigens by themselves as they produce short-term memory, no T cell immunity and not much antibody secretion

polysaccharide components are often conjugated to a protein carrier - e.g. outer membrane protein or diphtheria/ tetanus toxoids
- ensures longer lasting immunity, better immunogenicity

Question 23

how do polysaccharides conjugated to carrier proteins ensure better immunity? - mechanism?

Answer 23

B cell receptor takes up conjugated vaccine and presents it to naïve CD4+ T cells

differentiate and Th cells release cytokines to stimulate a T cell and antibody response - polysaccharide-specific antibodies generated

help T and B cell memory

Question 24

method for creating vaccine adjuvants?

Answer 24

adding/ conjugating additional elements to vaccines to enhance immunity and response - e.g. aluminium salts

aluminium salts are conjugated with the vaccine, form trapped particles and ensure a slow and steady release of antigen for a longer lasting immune response

Question 25

how do vaccine adjuvants improve immunity?

Answer 25

enhance immune response to antigen

promote uptake and antigen presentation

stimulate correct cytokine profiles

e.g. aluminium salts are conjugated with the vaccine, form trapped particles and create a slow and steady release of antigen for longer-lasting immunity

Question 26

why did the smallpox vaccine succeed?

Answer 26

vaccine programmes, case finding/ surveillance and movement control

effective vaccine, slow spread, poor transmission

no carrier states or animal reservoir

Question 27

why did the HIV vaccine fail?

Answer 27

high mutation rate - each HIV virion produced by an infected cell differs by at least one mutation

an effective vaccine would have to induce cytotoxic T lymphocytes - requires a live attenuated vaccine, danger of virulence reversion

Question 28

examples of passive immune treatments?

Answer 28

maternal transfer of antibodies

serum antibodies for prophylactic treatment