Immunity-L11- Vaccines II

what type of virus vaccines are available? (8) in COVID

1. attenuated- weakened virus that is live and less pathogenic

2. inactivated virus- formadelhyde and heat

1. replicating virus vector- virus delivers antigen and replicates in host

2. non replicating viral vector- virus delivers the antigen and doesn’t replicated

1. protein based- purified viral protein and adjuvant- such as the spike protein(NOVAVAX)

2. virus like particles- mimic viral structures without genome- empty COVID-19(Johnson and Johnson)

3. DNA/RNA vaccine- DNA- creates pores in membrane to uptake viral DNA spike protein gene. RNA vaccine- encased in lipid coat to enter cell(moderna, pfizer)

what are the main vaccinations for pertussis vaccines?

1. whole cell vaccine- highly protective, reactogenic(pain, fever) and induced th1 and Th17- pro inflammatory

2. acellular vaccine- 2-4 purifed adhesion proteins and adjuvant- moderately protective and minimal side effects. Th2 and Th17 response and less pro-inflammatory

in mice challenging- what T cell responses are needed for protection. experimental evidence and what knockout were used, what response etc

1. whole cell vaccination- Th1/Th17- clears bacteria

2. IFN gamma kick out mice- delayed clearance as Th1 is essential

3. IL-17A knockout- less neutrophils recruited- slower clearance- need Th17

4. acellular vaccine- induces Th2 and th17 and less ifn-GAMMA- LESS EFFECTIVE

TH1 RESPONSE IS MOST IMPORTANT!! Th2 is not sufficient!!!!

how can acellular pertussis vaccine be more effective?

add adjuvants that activate innate immune cells and DCs to make IL-12 for Th1 to make IFN-gamma for macrophages and B cells making opsonins and complement

and Th17 response for neutrophil recruitment

by adding adjuvant CpG- binds to TLR9 ligand which drives a Th1, but reduced Th17

what are the main roles of vaccine adjuvants?

• increase antibody titres

• drive Ab class switching

• direct differential of T cell populations

• tailor the immune response to the pathogen type ie CD8 for viruses

how do glycoconjugate vaccines work and why is the adjuvant important? for what bacteria/viruses?

to make a strong antibody response against bacterial sugar capsule like for bacteria that are capsulated like S.pneumoniae , H.influenzae and N.meningtidis

why are polysaccharides poor antigens?

• are T cell independent antigens and produce IgM and switch to IgG only

• T cells cant recognise polysaccharides so there’s no T cell help for class switching and poorly immunogenic

what is conjugate in the context in vaccines?

molecule made by liking/conjugating a weak antigen such as a polysaccharide to a strong antigen to a protein

how does conjugate improve the immunogenicity of a bacterial polysaccharide?

polysaccharides which aren’t very immunogenetics are conjugated to proteins

B cells recognise the sugar polysaccharide and T cell cells recognise the protein

• T cells allow class switching to IgG and memory formation

what are the issues with the MenB and creating vaccines for it?

• MenB sugars look like our sugars- so cannot use that and polysaccharides alone is poorly immunogenic