Treatment of chronic herpes infection based vaccines IFN - induced dendritic cell - Causes, Symptoms and Treatment .MF .
One of the important problems of modern infectology is a chronic relapsing form of herpes infection, herpes simplex virus types 1 and 2.From the frequency of relapses, and this depends directly on the quality characteristics of the patient's life.However, recurrence rate 6 and more times a year, with all seemingly "harmless" infection has a significant impact on the overall health of the patient.According to the WHO Regional Office for Europe herpes infection identified in a group of diseases that define the future of infectious disease in this century.
As you know, the manifestations of chronic herpes infection are quite specific and are manifested by single or grouped bubble elements with serous contents inside (vesicles) that appear in the background of the "prodrome" - the itching and discomfort at the site of future bubbles.Rash has its dynamic development: education in the dynamics on the ground crusts bubble and subsequent hyperpigmentation.The frequency of exacerbations of chronic infection and
manifestations of herpes simplex
developed regimens herpes infection include antiviral (acyclovir, valacyclovir, famciclovir, and others) and immunomodulating (interferons, inducers of endogenous interferon, Immunopreparat other groups) therapy, which effectively at some stage of the disease.Most regimens focused on subsidence of the acute illness, but did not aim at a long-term effect.Such treatment is not always sufficient to achieve the desired result - reduce recurrence to a minimum.A particular problem is the development of resistance (stability) viruses to antiviral drugs, especially used uncontrollably and without a prescription.In this regard, research and development went on.Develop drugs and vaccine therapy scheme chronic herpes infection.But these methods proved insufficient maximum activity.The turn to the latest research-based treatments using specific dendritic cells.
Dendritic cells (dendrocytes or DC) are cells of the immune system and are a special kind of white blood cells, which have branching structure (dendron-tree, Gr.).Dendritic cells have a relatively large size - up to 15-20 m and are located in almost all organs and tissues.Dendritic cells play an important role in the immune system - an antigen presentation function.In other words, in contact with microorganisms (viruses, bacteria, fungi, etc) in our body Dendritic cells absorb it with the help of phagocytosis process, and then use it antigens for "representation" specific immunocompetent cells to produce antibody (antigen-specific immune response).Dendritic cells are able to activate the high power immunocompetent cells such as CD4 T-lymphocytes iCD8.However, many research studies have shown a significant reduction of the dendritic cells in patients with chronic viral diseases, which is considered as one of the causes of long-term persistence of the virus in humans.
One of the modern methods of treatment of chronic recurrent form of herpes infection is based precisely on the presentation by dendritic antigen herpes virus cells in the presence of interferon-alpha and other components [ "Method for immunotherapy of chronic often recurrent herpes virus infection" patent RU2485962 on the basis of State Organization "Scientific Research Institute of clinical Immunology", Siberian Branch of the Russian Academy of medical Sciences (FGBU "NIIKI" SB RAMS) Ostanin AA, Starostin NM, Chernykh ER].
The aim of this method is to provide a dendritic cell of a new generation of vaccines that could solve one simple problem - reducing the clinical manifestations of herpes infection and reduce the frequency of relapses to a minimum by using cost-effective method of immunotherapy of chronic recurrent herpetic infection.Achieving this object is achieved by generation from peripheral blood monocytes of the patient autologous interferon-alpha induced dendritic cells loaded with recombinant antigen of herpes simplex virus in culture invitro, that the patient receives 2mya courses in conjunction with the preparation of recombinant interleukin-2 as an adjuvant (drug enhancing immuneanswer).It is due to IL-2 is a T-cell activation, are prevented apoptosis (cell death) lymphocytes, synthesis of long-lived cytotoxic T lymphocytes.
expected outcome of therapy is to develop a solid antigen-specific immune response to a high level for a long period of time.
Indications for treatment
indication for DC vaccination is a chronic herpes infection, often relapsing form at relapse rate of more than 6 times a year, and since the last recurrence interval of at least 2 weeks (ie, in remission).
How is the treatment of dendritic cells
Technical implementation of the method is as follows: The patient is hospitalized in a hospital, where held dendrokletok generation from peripheral blood of a patient.In the morning 200 ml of blood is taken into a vial with heparin (1000 U), to which is added zhelatinol solution (40 ml) and incubation carried out at 370 for 45 minutes.Formed leukocyte suspension which was centrifuged for 20 minutes at 1000 rev / min.The precipitated cells were washed by phosphate-zabufernym saline (PBS), layered over a density gradient fikkola-verografin and centrifuged again for 20 minutes, but at 3000 rev / min.The collected mononuclear cells (MNC) are subjected to an additional treatment (twice washed, resuspended) to the allocation of MNCs in a concentration of 3 x 106 / ml, which was incubated at 370 for 2 hours (it nezrelyedendrokletki).Subsequently, cells were again tested additional processing load of interferon-alpha of 1000 U / ml (Roferon-A, Roche, Shvetsarii), re-cultivating during 3 hours.Then, in the presence of drug polioksidony (NGO PetrovaksFarm, Russia) in a dose of 2 ng / ml, and the final maturation of dendritic occurs cells.
DK cells this way and received the IFN-DCs (interferon induced dendritic cells), which are subsequently loaded by the specific recombinant (artificially established in the laboratory) antigen of herpes simplex virus (HSV 1 gD, NGO"Diagnostic system" Lower Novgorod) at a dosage of 5 mg / ml by incubation for 1 hour at 370.
resulting preparation (specific IFN-DCs) at a concentration of 6.0 x 106 / ml cryopreserve for later use.The entire manufacturing process takes 4 days.
Technique of DC vaccination
Technique of DC vaccination using this drug consists of 2 courses of vaccine:
1) "inductor-rate" includes 4-6 subcutaneous injections in the upper third of the shoulder at a dose of 5.0 x 106 / mlat intervals of 2 weeks.Vaccinations are conducted against the background of the simultaneous administration of the interleukin-2 - drug "Ronkoleykin®" (LLC "Biotech", St. Petersburg) at a dose of 0.25 mg, which is administered subcutaneously as an adjuvant.
2) "Supportive Course" consists of 3-6 subcutaneous injections of IFN-DCs at a dose of 5 * 106 \ 1 ml at intervals once a month at the same time also with an adjuvant.
Monitoring the effectiveness of DC vaccination is carried out by determining the level of the proliferative response to stimulation MNCs vaccinal antigen of the herpes virus (HSV 1gD) and mitogen (Con A).The patient is taken 10 ml of venous blood, which is processed and evaluated within 72 hours and the level of other components proliferation studies.The result is given as the average account (imp / min) of the three identical cultures.Monitoring is carried out 4 times: before treatment, after 1 year, after the 2nd year and 6 months after the end of treatment (a recent study 15 months after the start of treatment).
Using this method of DC vaccination using IFN-DC vaccine showed 75% efficacy tion in patients with frequently recurrent form of herpes infection.Thus, the frequency of relapses in patients was reduced by 3 times, and the total area decreased and losses during exacerbations, duration of remission (interrecurrent periods) is extended up to 3 months or more.It was also noted improvements in the specific antigen-induced immune response after the second course of vaccination and 6 months after the end of treatment.
Thus, we can talk about a new effective method for DC-vaccine capable of stimulating production of an antigen-specific immune response not only in the period of vaccine, and 6 months after completion of treatment, which will undoubtedly affect the relapse rate for this disease and the quality ofof life in patients with chronic recurrent herpetic infection often.
infectious disease doctor Bykov NI