Vaccine 2 Flashcards
subunit vaccines are
isolated components of microorganisms e.g. individual proteins or polysaccharides
Subunit vaccine primarily provoke which response
antibody response
antibody response (6)
1) agglutination
2) opsonisation
3) neutralisation
4) activation of complement
5) inflammation
6) antibody-dependent cell-mediated cytotoxicity
protein processing pathways
CD5 T response- MHC2
CD8 T response-MHC I
CD4 T cell response
proteins processed via endosomal pathway, which causes inflammation, macrophage activation and antibody production
CD8 T cell response
proteins processes via cytosolic pathways
- kills infected cell
- cytotoxic T cell
polysaccharide sub-unit vaccines are based on the fact
that all bacteria are coated in sugar
- different bacteria have very specific sugars- which makes them good vaccines
the different combinations of polysaccharides make up
unique cell surface structures
- antibodies can be are again
the different combinations give arise to
immunologically distinct polysaccharides
Streptococcal pneumoniae is the
Major cause worldwide of community acquired pneumonia, bacterial meningitis, bacteraemia and otitis media
- causes systemic infections which are hard to treat due to the time of diagnosis being to late
Streptococcal pneumoniae is a bacteria
that had an abundance of polysaccharide on its outer layer
how are antibodies protective against streptococcal pneumoniae
opsonising- mostly
complement fixing
issues with developing streptococcal polysaccharide vaccines
different strains have different polysaccharides on their surgave
how many serotypes of pstreptococcal polysaccharide
90
how do you develop a vaccine which has a potential of 90 different strains
o focus on the most abundant serotypes (the ones most likely to cause disease)
o especially meningitis and bacteraemia
currently how many serotypes in vaccines against streptococcal pneumoniae
23
Although the very group we want to protect against are the you and elderly do not respond well to polysaccharide vaccine
no memory, weak immune system
- adaptive immune system is weak
why do polysaccharides provide weak immunity in the young and elderly?
polysaccharides are not processed i the same way as proteins e.g. - through the CD4/CD8 pathways- so don’t get protective responses such as cytokines, which cause inflammation, antibody production, macrophage activation
- cannot stimulate CD4/CD8
- immature antibody response
immature antibody response with Streptococcal pneumonia vaccines
very few IgG- dominated by IgM- directly interact with b cells
- clonal proliferation of B cells
how can we get around the issues surrounding streptococcal polysaccharide infections
- link the polysaccharide to a protein carrier
- means that it behaves more similarly to proteins
- turning o T cell activation
- MHC class 2 see the peptide and polysaccharide fragment
- more IgG
example of a protein that can be tagged to the strecptoccal vaccine
diphtheria CRM197 toxin ( which is genetically modified- activate site region mutated to abolish toxicity)
conjugate vaccines
are predominately used against streptococcal disease mix between polysaccharides linked to a protein carrier)
streptococcal disease is a massive killer
in developing countries
23-valent vaccine
¥ Pick the serotypes most likely to cause disease.
¥ Isolate polysaccharides from these serotypes (1, 2, 3, 4, 5, 6b, 7F, 8,9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F)
what type of antigen are polysaccharides
T cell independent antigens
Polysaccharides are t cel idnepdnent antigens
no involvement of antigens presenting cell, CD4+/8+ T cells.
- polysaccharides interact directly with B-cells
Polysaccharides interact directly with
B cells
- clonal proliferation of B cell
- production of IgM antibody
- poor antibody response in children and elderly
- no memory
conjugate vaccine
chemically couple protein- polysaccharide vaccine
example of polysaccharide vaccines
¥ Streptococcus pneumoniae - pneumonia ¥ Haemophilus influenzae - pneumonia ¥ Neisseria meningitidis - meningitis ¥ Salmonella typhi – typhoid fever ¥ Burkholderia pseudomallei - melioidosis
mechanisms of T-cell activation by glyconjugate vaccine
1) glycoconjugate vaccine is internalised into an endosome of theB cell and processed into glycansaccharides and glycanpeptides
2) MHC II presentation of glycol peptide by MHC II to the ab receptor of CD4+ T cells
4) activation of the T cell by the carbohydrate/MHCII results in T-cell production o cytokines which mature the b cell to become a memory B cell
vaccines which induce CD8+ T cell responses
- subunit vaccines evoke CD4= endosome
- we need a vaccine which gets into the cytosol
which diseases required CD8+T cell response to clear infections
TB Salmonellosis Meliondosis Viral infection- yellow fever, influenza, measles Cancer vaccines
CD8 T cell response is required anytime
where killing of host cell is required
pathogens which growth within infected cell
require a response where the whole cell is destroyed
it is difficult to develop vaccines
which induce CD8+ T cell responses
CD8 T cells
kill via cytotoxicity
approaches which induce a CD8 T cell response from vaccines
1) use live attenuated microbes
2) using naked DNA vaccines
Using live attenuated microbes to induce a CD8 T cell response
capable of replicating inside the cytosol- presenting protein antigens to the immune system via CD8 T cell responses
- can survive long enough to establish an immune response
- balance between over and under attenuation
issues with live vaccines
may not be able to control infection by attenuated strain
Using naked DNA vaccines to evoke a CD8 T cell response
- identify and produce gene coding for vaccine compoenent- protein
- DNA is taken up into cytoplasm (muscle cells( and transcribed and translated
- generate specific antigenic proteins
- an immune response develops
- cytosol response stimulates CD8 T cell responses
issues with DNA vaccines
- difficult to control duration of exposure- how long the DNA will survive
- works well in animals but not humans
in theory DNA vaccines
combine the advantage of live and sub-unit vaccines
e.g. West Nile Fever vaccine licensed for use in hordes – vaccines encode coat proteins
e.g. Infectious hematopoietic necrosis vaccine licensed for use in fish- vaccine encode surface glycoprotein
summary
- polysaccharides are often included in vaccines
- to improve the response to the vaccine they are linked to a protein
- developing vaccines which induce CD8 T cell responses is difficult
