Comparing the safety and immunogenicity of a candidate TB vaccine MVA85A administered by intramuscular and intradermal delivery Flashcards
Why did the group want to compare intradermal versus intramuscular vaccination against TB?
The researchers hypothesized that the intramuscular route of administration was NOT inferior to the intradermal route.
Ultimately, the researchers wanted to determine if ID administration was just as efficacious as IM administration.
What is the importance of assessing IFN-gamma production as a measure of effectiveness for a TB vaccine?
IFN gamma is a macrophage and NK cell activator and the assy used to measure its release measure a person’s immune reactivity to M. tuberculosis.
In the context of this clinical trial, the stronger the release of IFN gamma, it was infered that the vaccine induced a strong and sustained antigen-specific response.
How did the authors determine whether there was an antigen-specific response due to the vaccination?
The authors determined this by performing an IFN gamma ELISpot assay.
The higher the levels of IFN gamma produced, the stronger the vaccine stimulated an antigen-specific response.
The authors also performed an Area Under Curve (AUC) analysis to measure this effect statistically.
Why did the authors add anti-CD28 to the wells of the microtiter plate for one of the assays?
CD28 is a molecule on the surface of T cells that provides co-stimulatory signals that are required for T cell activation. This activation leads to the production of a variety of interluekins.
The use of anti-CD28 partially mimics stimulation of T cells by antigen-presenting cells.
Why are SEB [Staphylococcus enterotoxin B] and PHA [phytohemagglutinin] used as positive controls (Basically, I want to know what these two compounds are doing in the assay as done in the paper)?
Positive controls are groups where a phenomenon is expected. That is, they ensure that there is an effect when there should be an effect, by using an experimental treatment that is already known to produce that effect (and then comparing this to the treatment that is being investigated in the experiment).
In the context of this experiment, these positive controls are being used to test the validity of the experimental procedure. These two compounds are known to stimulate IFN gamma release.
The authors looked at chemokine receptor expression on peripheral blood mononuclear cells. Why did they do this?
The authors examained chemokine receptor expression on the PBMC’s as a measure of cytokine / interluekin production as well as an overall stimulation of the T cell response.
The upregulation of the chemokine receptor would indicate that there was a positive stimulation of T cells and cytokine / interleukin production.
Much of the paper compared ID versus IM vaccination and the authors stated that there was no significant difference between the two methods. However, there was one immunological ass that was significantly different between the two methods of vaccination. What was this difference and why might this immunological difference have occured?
The only difference between the two methods was that the median antigen-specific IFN gamma response in the ID group exceeded that of the IM group.
On page 1 of the paper, the authors state that the skin plays a significant & special role in the innate and adaptive immune responses. It is highly vascularized, has good lymphatic drainage and contains a good supply of antigen-presenting cells. These cells are able to cross present antigen and this in turn allows for a rapid induction of cell mediated immunity. The authors suggest that the ID route may be the optimal site of injection for the TB vaccine.
