Vol 62, No 5 (2017)

The review presents the results of the analysis of domestic and foreign scientific literature on the interchangeability of hepatitis A, B and influenza vaccines. The WHO materials, regulatory documents, data from scientific literature of foreign countries and Russia about the vaccine interchangeability are summarized. The problem of objective assessment of interchangeability of drugs is relevant worldwide. The definition of an “interchangeable drug” does not draw a clear line between the interoperability criteria for chemical and immunobiological drugs. The official guidance documents on immunization adopted in several countries define “interchangeability” as the practice of transition from a vaccine available from a certain manufacturer to a similar vaccine available from another manufacturer. The term “interchangeable” can be applied to immunobiological drugs if one of the drugs can be replaced with the other in the course of vaccination. The concept of interchangeability applies to vaccines that do not differ in efficacy (immunological, preventive, epidemiological) and safety and are used in an immunization course involving multiple administration of these vaccines. The definition of interchangeability is important in order to address the problem of replacing unidirectional vaccines available from different manufacturers when purchasing vaccines included in the national schedule of preventive vaccinations and in the schedule of preventive vaccination on epidemic indications. One of the most important conditions for “interchangeability” of vaccines is their application in accordance with the recommended schedule of administration and the dosage indicated by the manufacturer. Research data show that vaccines can be interchangeable if used in accordance with the recommended schedule of administration and the dosage specified by the manufacturer. Control agencies of many countries issue recommendations regulating the procedure of vaccine replacement in case of necessity. However, there are no special regulations of vaccine interchangeability in Russia. The concept of vaccine “interchangeability” should be extended to the continuation of a course of vaccinations in a particular person with a vaccine of another manufacturer and the possibility of applying similar vaccines available from different manufacturers.

The combined action of the immunostimulatory drug Stimforte and the basic etiotropic drug acyclovir commonly used to treat herpes infections was studied using the model of lethal experimental infection of mice BALB/c with herpes simplex virus type 1. It was found that the interaction of these drugs is additive. In addition, Stimforte inhibits infection caused by a strain of virus, which is highly resistant to acyclovir. When administered 24 hours prior to HIV-1 infection of human lymphoblastoid cells MT-4, Stimforte exhibited reliable antiretroviral activity best expressed during the early period of infection (the 3rd day). On the 6th day of observation the effect was almost completely lost. Combined use of Stimforte at a dose of 50-100 µg/ml with a subthreshold dose of retrovir (0.03 µg/ml) had a synergistic antiviral effect. Thus, Stimforte, which exhibits, on the one hand, antiviral activity against viruses of different families and, on the other hand, the immunomodulatory properties, could be promising as an etiopathogenic tool in helping to normalize both nonspecific and specific immunity. It may be used simultaneously with etiotropic antiviral chemotherapy in treatment of generalized herpes infection in patients with immunodeficiency. Furthermore, Stimforte can be used in the case of development of drug resistance in HSV, in particular, in HIV-infected patients.

Characteristics of the effect of attenuated rabies virus strain «Moscow 3253» on morphological parameters of transplantable line Vero cells were studied by atomic force microscopy (AFM). Methods based on phase contrast microscopy and immunofluorescence were used to confirm the specificity of interaction and to identify the infectious activity of the rabies virus. Images of intact Vero cells and Vero cells infected with rabies virus were obtained at different periods of cultivation. The character of changes in the cell dimensions (length, width, height) and the cell membrane roughness depending on the rabies virus cultivation time was determined. During the observation period both increases and decreases in the size of the cells were recorded. The size of the infected cells exceeded that of the intact. An increase in the membrane roughness in cells exposed to rabies occurred during the entire period of observation, since the first hours of the interaction of the virus with the cell, while the intact Vero cells exhibited only minor changes in the membrane surface roughness, which were not dependent on the age of the culture. The dependence of the increase in the cell membrane roughness on the infecting dose of the rabies virus was determined. The obtained results open up the prospect of developing a methodological approach to the quantitative in vitro evaluation of the rabies virus using AFM. Changes in the cell membrane roughness appear to be the most indicative parameter for such evaluation.

The immunologic activity (specific activity) is one of the main indicators of quality of vaccines for prophylaxis of hepatitis B, along with their safety. Retrospective analysis of the use of laboratory methods for assessment of specific (immunogenic) activity of modern vaccines against hepatitis B using indicators was carried out: in vitro method based on evaluation of HBsAg content and in vivo method based on evaluation of immunogenic activity in mice. Both methods are standardized and described in normative documents on the vaccines against hepatitis B of domestic production registered in the Russian Federation. Indicators of specific (immunogenic) activity of vaccines against hepatitis B were used to investigate more than 170 vaccine series using the ELISA method in the period from 2013 to 2015. The obtained control results confirmed the expediency and efficiency of enzyme immunoassay for determination of HBsAg content, as well as permissibility of use of ready sets of the Murex HBsAg Version 3 test systems for testing vaccines against hepatitis B by the ELISA method. Analysis of the results of laboratory control of series of vaccines against hepatitis B using a biological method for immunogenicity evaluation based on ED50 analysis confirms persistently high immunogenic activity of the Russian commercial vaccines intended for prophylaxis of hepatitis B. The confirmed comparability of methods allows the number of in vivo tests to be further reduced in favor of the enzyme immunoassay authentically characterizing the produced drug.