MODERN STATE OF VACCINE DEVELOPMENT, DNA VACCINES
1 Riga Stradins University, Riga, Latvia
2 Karolinska Institutet, Stockholm, Sweden
* Corresponding author.
Introduction: DNA is a rapidly developing vaccine platform for cancer, infectious and non-infectious diseases. The objective is to overview the progress in development of DNA vaccines against infectious diseases and cancer, and share experience in development and applications of experimental DNA vaccines.
Objectives: To give overview of methods used in design of DNA immunogens, their delivery, and approaches to screen the immune response induced by DNA immunization, evaluate its efficacy and prognose performance in human applications.Kew words: DNA-immunogen; synthetic genes; targeting of processing; delivery by electroporation; optimization
Plasmids used as immunogens encode proteins to be further synthesized in vaccine recipients. DNAs are mainly synthetic, ensuring enhanced expression. Their introduction into the host induces antibody and cellular responses. The latter are often more pronounced, and mimic the events occurring in infection, especially viral. There are few distinct ways by which the vaccine antigen can be processed and presented, which determine the resulting immune response, and which can be manipulated. Routenly, the antigen synthesized within the host cell is processed by proteasome, then loaded onto, and presented in complex with MHC I molecules. Processing can be re-routed to lysosome, or immunogen can be secreted to be further presented in complex with MHC II. We have tested both approaches, using a panel of signals for retargeting of prosessing, the best were signals from Lysosome Associated Memberane Protein I ensuring MHC class II presentation and induction of a mixed Th1/Th2 type of immune response. Apart from the level of immunogen expression and processing/presentation route, vaccination efficacy depends on DNA delivery. DNA immunogens are generally administered by intramuscular or intradermal injections, usually followed by electroporation, which enhances delivery by 1000-fold. In Vactrain project, we have accummulated vast experience in electroporation of plasmid DNA into rodents, and lately also non-human primates, with successful induction of specific immune response. Other techniques are also used as noninvasive introduction by Biojectors, skin applications with plasters and microneedles/chips, sonication, magnetofection, and even tatooing. An intense debate on the pros and cons of different routes of delivery is ongoing. A number of studies have compared the effect of delivery methods on the level of immunogen expression, and magnitude and specificity of the outcoming immune response. According to some, delivery route determines the immunogenic performance, according to others, it can modulate the level of response, but not its specificity or polarity. Our data obtained in Vactrain project supports the latter option.
Conclusions: Progress of research aiming at optimization of DNA vaccines design, delivery, and immunogenic performance led to marked increase in their efficacy in large species and man. New DNA vaccines to use in treatment of infectious diseases, cancer, allergies and autoimmunity are forthcoming.
Acknowledgments: Horizon2020 project VACTRAIN 692293, and LZP-2018/2-0308.
Bioorganic Chemistry, Chemical Department, Lomonosov Moscow State University, Moscow, USSR
PhD student at the Academy of Medical Sciences USSR;
PhD thesis, University of Fine Chemistry and Technology, Moscow, Russia;
Post Doc, Department of Virology, National Bacteriological Laboratory (SBL), Stockholm, Sweden;
Docent in Immunology at Karolinska Institutet, Stockholm; renewed 2013;
Laboratory Animal Science 4.5 ECTs, Karolinska Institutet, FELASA certificate ID 658.
present, Experienced researcher; Riga Stradins University, Riga, Latvia;
Associated professor, Karolinska Institute, Stockholm, Sweden
Microbiologist, Swedish Institute for Infectious Disease Control (SMI), Stockholm
Research Fellow, Fund for Internationalization of High School Education and Research (STINT) at the Swedish Institute for Infectious Disease Control;
Guest Researcher, Swedish Institute for Infectious Disease Control, Stockholm;
Researcher, D.I. Ivanovsky Institute of Virology, Moscow, Russia
Engineer, Chemical Department, Moscow Lomonosov State University, Moscow