What is an adjuvant ?
Substance added to vaccine to boost or modifie immune response; makes more effective
What do adjuvants do ?
Adjuvants help:
-Immune system produce stronger and more durable response to the vaccine’s antigens.
-Reduce amount of vaccine needed
-May reduce minor, temporary reactions e.g. small lump/redness
What is a common example of an adjuvant and what does it do ?
Aluminium salts are most widely used adjuvant in human immunisation
-Acts as a depot, prolonging exposure
-Activates inflammasome in macrophage
-Induces cell damage and danger signal leading to dendritic cell activation and migration
Depot = aluminium stays at injection site, antigen clings to aluminium, antigen slowly released
What is the ultra mega goal of vaccines ?
To make long lived plasma cells in the bone marrow
Describe how administration of a vaccine leads to immunit
1) Vaccine target and adjuvant is injected into upper arm
2) Local immature dendritic cells are activated via adjuvant and take up vaccine protein
3) They migrate to local lymph nodes where the process and present peptide from the vaccine to T cells (both CD4+, MHC Class II and CD8+ T cells, MHC Class I )
4) CD4+ T cells that are peptide specific are activated and differentiate to become helper T cells helping both B cells and CD8+ T cells
5) Antibody and CTL are produced that are specific for the vaccine
6) Immune memory is also produced both long lasting memory B cells and T cell memory
Think of it as a numbers game- the more often you see the antigen the better the response
What is attenuation ?
Some vaccines use a live attenuated virus which has been weakened
-Nasal vaccines always use live attenuated pathogens
-e.g. flu and old polio vaccine
What is a conjugated vaccine ?
Some bacteria have polysaccharides on their surface which make for bad antigens as stimulate T cell independent response
-Polysaccharides attached to a carrier protein which is strongly antigenic; immune system now cares about polysaccharide
-Protein causes T-cell-dependent response; stronger, longer lasting immunity
Exclusive against bacteria
What are examples of bacteria which conjugated vaccines are used against ?
Young children are very susceptable to (invasive) pneumococcal infection when <4yo
-Make very poor immune responses to polysaccharides as their
splenic immune response is not mature
-Conjugated vaccines for pneumococcus, Hib and Meni
What is a nucleic acid vaccine ?
They provide genetic material (DNA or RNA) that instructs the body’s cells to produce the vaccine antigen.
What are the advantages of a nucleic acid vaccine ?
-They are safe because there is no risk of infection or integrating into host DNA
-Trigger strong T and B cell immune responses because they are manufactured by your own cells
-Are easily manufactured
What are the disadvantages of a nucleic acid vaccine ?
-Ultra Cold storage
-Boosters are required
-Regulatory hurdles
What disease needs only a single dose of vaccine to be permanantly and full-on imunised against ?
Yellow fever
What determines if immune memory can protect against infection ?
1) Incubation time of pathogen
2) Then quality of the memory response
3) The level of antibodies induced by memory B cells
Antibody levels in the circulation wane after primary immunization, often to below protective levels
Describe the impact of incubation period on vaccine possibility
Long incubation period
-Allows the days required for an adaptive secondary antibody response to develop
-Vaccine can be given after expore
-e.g. hep B
Short incubation period
-If we relied on a single vaccine dose (after exposure) it would not produce antibody levels sufficient to be protective
-Preexposure boosters are necessary
-e.g. Haemophilus influenzae
What are preventative cancer vaccines ?
sstop infections which cuase cancer, e.g;
-Human Papillomavirus HPV; cervical, anal and throat cancers
-Hepatitis B virus; liver cancer
What are therapeutic cancer vaccines ?
Stimulate the immune response to attack cancer cells through antigen recognition
What are examples of theraputic cancer vaccines ?
-Personalised neoantigen vaccines; personalized to that patients cancer
-Cell based vaccines; Whole cancer cells or dendritic cells - prostate cancer
-Peptides and Viral vector vaccines - melanoma
-BCG (bacillus tuberculosis Guerin) - early bladder cancer, also preexposure in TB