I would like to know if proteins expressed in higher quantities, such as DNA polymerase, would be better vaccine candidates for a T-cell based vaccine.


To find candidate proteins which can be used as peptide vaccine, these need to fulfill some criteria:

  • The most important is that the peptide (or protein) used for
    vaccination shall not have a closely relate sequence in the organism in which the vaccination shall occur. Otherwise either no reaction (due to immunologic tolerance to self) or an autoimmune reaction might happen.
  • The peptide/protein need to be expressed on the surface of the microbe (either virus or bacteria) since otherwise it will not be recognized by the immune system. Also domains of a potential vaccine candidate which are inside of membrane are not useful.
  • The epitope needs to be stable enough to be used as a vaccine and also be present on the microbe (otherwise there is no immune reaction).

If you want to read further on this topic, there is an interesting Paper from the WHO available, which gives a nice introduction:

To answer your question: No, these proteins cannot be used for this purpose, as they are relatively closely related to the same proteins in the human body. This will probably lead to no immunologic reaction at all. Additionally, these proteins are located inside of cells and thus not exposed to the immune system.

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    $\begingroup$ I have doubts about the second statement. If virus replicates inside the cell, virus will let some proteins located inside cells to proteasome degradation and thus will be exposed via MHC, thus revealing to CD8+ cells that has been infected. $\endgroup$ – biotech Oct 24 '14 at 20:53
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    $\begingroup$ @Bernardo When a virus infects a cell it basically takes over. In most cases the cell is lost and destroyed when the viruses are set free. Additionally you want to find and inhibit the virus when it enters the body, not when it already had time to replicate. This is something you will achieve only when you recognize the virus. $\endgroup$ – Chris Oct 24 '14 at 21:04
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    $\begingroup$ I agree that neutralizing antibodies are a good strategy to prevent a new cell infection. But, why are T cell-based epitops have that hype? ncbi.nlm.nih.gov/pubmed/22044118 ncbi.nlm.nih.gov/pubmed/24358361 $\endgroup$ – biotech Oct 24 '14 at 22:55
  • $\begingroup$ I don't understand this either - this approach always needs the professional antigen presenting cells which present the antigen on their MHC-molecules. So T cells do not stand alone. $\endgroup$ – Chris Oct 25 '14 at 10:18
  • $\begingroup$ @Bernardo Chris is right, you are not able to activate CD8+ T-cells without APC. So you need a badly infected APC or an APC presenting your protein on MHC1/MHC2 and a CD4+ T-cell which verifies that it is really a pathogen. I am not certain whether it is possible to achieve T-cell response by vaccination, but it is certainly harder than to achieve B-cell response... $\endgroup$ – inf3rno Oct 26 '14 at 7:21

The original question asks about vaccine development against a virus. Most effective anti-viral vaccines elicit antibody responses that presumably protect via neutralization of viruses as they enter the body. Bob Seder has a good review on this - you may find a discussion relevant to this topic in the section titled "Viral targets for the induction of humoral immunity". These vaccines would not necessarily be leading to the destruction of infected cells as this is a CTL function.

I think the hype that biotech is referring to is in relation to therapeutic vaccines against cancer, etc. that elicit CTL responses capable of destroying cancer cells. However, it is also important to keep in mind that both CTLs and B Cells need CD4 T Cell help in order to develop - nothing stands alone in the immune system.


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