theoretical Cytomegalovirus vaccine

A)     Vaccine formula

The vaccination process passes through two steps.

Vaccine’s first step contains peptides. Peptides can be obtained from, life attenuated zombie virus with adjuvant. Life attenuated zombie virus degradates to peptide in DC and makes the cells to recognize the ZCMVs, and thus making proliferation of CD8+.

The second step of vaccine contains IFN-γ. It is a crucial part of the vaccine since it provides the MHC I to appear on the cell surface. If we did not introduce IFN-γ, there would be no way to recognize the infected cells with ZCMV. It is because the ZCMV downregulates the MHC I.

B)     Regimen

For the proliferation of specific CD8+ cells to the ZCMV it is enough to inject its , life attenuated zombie virus only once. If we inject it in the childhood the memory cells will remain for the whole life.

The remaining part is introducing the IFN-γ. We may inject it to a patient after he/she was exposed to ZCMV.

C)     Route of delivery

Both steps are injected to human intravenously, because it is the most straightforward way to deliver the vaccine and the easiest way to its proliferation.

 d) mechanism of action

“cross-presentation: for viruses that do not infect DCs, virus can be taken up and degraded in the endocytic pathway and then transferred to the cytosolic pathway for presentation on MHC I” (citation from slides).

First we decided to infect intravenously, life attenuated zombie virus with adjuvant, such as oxidation-sensitive polymersome + gardiquimod as payload. This adjuvant help to activate CD8+ by inducing production of IL-6 and Il-12 in DC. [1]

For antigen presenting cell such as DC to present molecule on the MHC-I following steps take place. Virus first engulfed and put into phagosome. Then, Phagosome (with virus inside) fuses with lysosome, and virus broke to smaller pieces. During the degradation some of the protein part escape from phagolysosome and goes to cytosol. Those peptide particles now called endogenous antigens. Endogenous antigens degradate to smaller peptides by proteasome. After that, TAP proteins then transport peptide to ER. In ER peptides bind to MHC-I. ER transport MHC-I (with peptide) molecule to Golgi complex. Golgi complex transports MHC-I to membrane, where it display it.  DC then present MHC-I to CD8 cell and activate it. After that person has activated CD8 T cell. Another problem is downregulation of HLA in infected cell. It can be solved by INFy. INF-y can increase expression of MHC I and II.

Reference:

1.      Scott EA, Stano A, Gillard M, Maio-Liu AC, Swartz MA, Hubbell JA. Dendritic cell activation and T cell priming with adjuvant- and antigen-loaded oxidation-sensitive polymersomes. Elsevier, 2012.