RNA based vaccines.
The recognition that CD8(+) T-cell mediated Th1 immune responses were necessary to produce immunity to intracellular and transformed self pathogens led to intense interest in the delivery of nucleic acids, DNA, or RNA encoding candidate antigens, as vaccines. Antigen presenting cells (APC) encounter most protein and vaccine immunogens as extracellular proteins and, thus, present them on major histocompatibility complex (MHC) class II molecules leading to the activation of CD4(+) T cells. Protein antigens encoded by nucleic acids delivered to dendritic cell (DC) are produced inside the cell and, thus, can stimulate MHC class I mediated activation of CD8(+) T-cell immune responses. Unfortunately, DCs are not readily transfected with DNA (Akbari et al., 1999) resulting in the requirement for high concentrations of DNA and repeated immunizations to achieved immune responses. RNA, on the other hand, is readily taken up and expressed by DC, making it an alternative vaccine candidate. In this article, we will discuss immune responses developed, interactions between APC and RNA that activate and dictate DC activation, and preliminary studies using RNA in vivo and in vitro to develop protective immunity.
Cannon
Georgetta
G
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Weissman
Drew
D
D000276:Adjuvants, Immunologic; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005544:Forecasting; D006649:Histocompatibility Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D012313:RNA / Q000276:immunology*; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D014779:Virus Replication
D000276:Adjuvants, Immunologic; D006649:Histocompatibility Antigens; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D012313:RNA