Preliminary evaluation of mRNA as as versatile vaccination platform against infectious diseases
Infectious diseases kill millions of people every year. Despite quickly evolving technology, vaccination remains the most efficient way to prevent and treat them in most regions of the world. Vaccines are based on the immunological memory of adaptive immune system. For achieving the most effective response of this part of immune system, a prior activation of innate immunity is required. In this process, dendritic cells (DC) represent the main connecting link between the two systems. DCs are professional antigen presenting cells (APCs), capable of antigen acquiring, processing and presenting it to T cells. Because of their important position in the activation of adaptive immune system, DCs represent an important target model for vaccine production. So far, most clinical studies have used these APCs for specific activation of cytotoxic T cells (CTLs), which are the only cells being able to completely eliminate viral infection. Recently, there a growing interest in using mRNA as a vaccine platform to activate DCs has evolved, mainly due to its favorable safety profile and ability to efficiently activate cell-mediated immune responses. Actually, mRNA-vaccines offer a compelling alternative in preventing and treating various infections, as they can be rather quickly produced, are transiently expressed and suitable for encoding different antigens. For these reasons, we set up to evaluate feasibility and efficiency of intranodal immunization of mice with mRNA-based vaccines in evoking antigen-specific T and B cell immune responses. For our experiments we used three mouse-models, HIV-1, LCMV and influenza A virus. Depending on the model, mRNAs were encoded with different viral antigens (HIVACAT, NP, gp and HA) and adjuvants (TriMix: CD40L, CD70 and caTLR4; DiMix: CD40L and caTLR4; and flagellin). We demonstrated that intranodal immunization of mice with mRNA-vaccines can generate strong antigen-specific T-cell and B-cell immune responses. With a concomitant application of the TriMix mRNA we achieved stronger CTL responses following the first and the second, but not after the third immunization. In contrast, flagellin enhanced humoral immune responses to influenza hemagglutinin (HA) but turned to be immunosuppressive in regard of CTL activation. Our preliminary experimental results are only a small contribution to the complex field of mRNA-vaccines development, but they suggest that by continuing research in this direction the efficiency of fighting various types of life-threatening diseases could be improved in future.
2017
2020-09-21 08:33:23
1033
mb22
[Š. Jug]
Špela
Jug
70
Matjaž
Jeras
991
Joeri
Aerts
994
UDK
4
614.47:615.37(043.3)
COBISS_ID
3
4408689
MAG_Jug_Spela_2017.pdf
934392
Izvorna datoteka
2020-09-21 08:48:50