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28 Cards in this Set
- Front
- Back
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What sort of immune response does alum cause? |
Antibody, Th2 skewed Not a very good T-cell response |
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Morphology of aluminum oxyhydroxide/ alhydrogel? |
Poorly crystalline |
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Morphology of aluminum hydroxyphosphate/ AdjuPhos? |
1-20um clusters/ aggregates of 50nm nanoplates Completely amorphous |
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Aluminum oxyhydride binds to ____ charged Ag. |
Negatively |
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Aluminum hydroxyphosphate binds to ___ charged Ag. |
Positively |
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How are antigens adsorbed into aluminum? |
Both alums have hydroxy on the surface that can undergo ligand exchange with phosphate groups on the Ag. Can even work with electrostatic repulsion.
More phosphates = more adsorptive |
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Why is free phosphate added to vaccines? |
Free phosphates compete with antigens and the adjuvent. This decreases strength of interaction between Ag and adjuvent. |
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What happens to alum in vivo? |
AdjuPhos rapidly dissolves Alohydrogel slowly and incompletely dissolves under physiological conditions |
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What is AS04? |
A next generation alum-based adjuvent, basically a non-toxic form of LPS that is adsorbed onto aluminum oxyhydroxide particles. It has improved Th1 response compared to aluminum oxyhydroxide alone, but does not make t-cells. |
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What is Imiquimod? |
A TL47 agonist, and a potent adjuvent for therapeutic vaccines, but diffuses too quickly due to low MW. |
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How can imiquimod be improved? |
Can modify by adding phosphate group, and can be adsorbed via ligand exchange to form an alum depot. Alum holds imiquimod longer at site of administration. |
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What are VLPs? |
Virus like particles - viruses that can't replicate/ non-infectious. These are the same size as normal cells (50-75um) and can be phagocytosed by APCs. |
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What are ISCOMs? |
Immune stimulating complexes. Spherical, cage-like structures that spontaneously form upon mixing cholesterol, saponaria saponins and phospholipids. This allows for insertion of antigens that are amphipathic. - used for influenza membrane antigens -50-70nm |
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What are virosomes? |
"Fancy liposomes" Phospholipid membranes incorporating viral proteins into the surface of the particle and inside the compartment of the virosome. 100-200nm in diameter |
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What is MF59? |
Microfluidized O/W emulsion made of squalene oil and Tween 80 and Span85. Another adjuvent with acceptable safety profile. |
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MOA of MF59? |
Increases local cytokine and chemokines, and increases cell recruitment. Improved antigen uptake by monocytes. |
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What are the benefits of PLGA nanoparticle and microparticle vaccines? |
- can hold and protect antigens - can have continuous or discontinuous release of antigens - able to modify shape and size - ability to modify and functionalize particle surface |
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What are drawbacks to PLGA vaccines? |
- Degrades and releases lactic acid, which can change the protein structure of antigen - Also costs a lot and hard to manufacture consistently |
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How can you improve/ solve the problem with PLGA microspheres? |
1. Use buffer salts to prevent substantial pH drop 2. Use polyphosphazenes instead cuz they degrade to make a neutral microenvironment |
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Does the site of injection matter for a. live attenuated vaccines b. non-live vaccines |
A. No, go stick that needle anywhere yolo B. Yes. Need to stick in a DC rich site. Skin is high in DC, muscle moderate, fat low. |
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How far should needles go to administer non-live vaccines? |
Approximately 1.2mm. Use mantoux method cuz doctors suck. |
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What is poke and patch method of microneedles? |
Uncoated microneedle makes holes in skin Apply vaccine |
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What is poke and release method of microneedles? |
Microneedle is made up of polymeric matrix of with the antigen. Entire needle dissolves. |
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What is coat and poke method of microneedles? |
You coat the microneedle with the antigen with a dry-film and go stabbity stab stab. Antigen released upon application. |
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What are the advantages of hollow microneedles? |
Vaccines can be injected as a liquid, and you can precisely control how much is injected. |
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True or false: 3um and 6um flu vaccine injected ID is equal to 15um flu vaccine injected IM |
True |
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What is intercell TCI patch? |
An abrasive strip disrupts stratum corneum, and then a patch with a vaccine is applied. The antigen are then taken up by langerhan cells. |
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Why do mucosal vaccines require live attenuated viruses? |
Mucosal often creates tolerogenic response (interprets antigen as normal flora/ beneficial) so a live virus creates a stronger response. |
