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Aim: Evaluate safety of prophylaxis of viral hemorrhagic fevers by specific heterologous immunoglobulins., Materials and Methods: Clinical-laboratory examination of 24 individuals after intramuscular administration of heterologous Ebola immunoglobulin was carried out. Anaphylactogenicity of the immunoglobulins was studied by WD 42-28-8-89 in guinea pigs compared with commercial preparations., Results: Immediate type reactions were not observed. In individuals with normal anamnesis the number of local reactions was 31%, general in the form of lung serum disease - 13%. In individuals with unfavorable anamnesis against the background of desensitization therapy there were almost no reactions; without it local reactions were present in 50%, mild severity serum lung disease - in 17%, medium - in 33%. Immunoglobulins against especially dangerous viral agents by anaphylactogenic properties did not differ from commercial heterologous preparations., Conclusion: Application of specific immunoglobulins from horse blood sera (the main means of protection from dangerous and especially dangerous exotic viral infections) with compliance by desensitization principles is relatively safe. Safe level of sensitization properties is characterized by anaphylaxis index up to 3.7 for guinea pigs.

Clinical trials of oral live recombinant embryonic variola and hepatitis B bivaccine as tablets (Revax-BT) were performed. When volunteers were prevaccinated with oral variola vaccine first in a small dose and, 7, 14, 30, 90, and 180 days later, in a larger dose, a slight reactoginicity was sometimes observed after the first vaccination (with a small dose) whereas revaccination with a larger dose did not give rise to any clinical manifestations. A month after vaccination, a protective level of virus-neutralizing antibodies to vaccinia virus (VV) was observed in 90-100% of the volunteers twice immunized with the bivaccine (in a small dose and in a larger one at an administration intervals of 1-2 weeks under remote revaccination while 6-9 months following vaccination, this level was recorded in 80% of the volunteers. A month following vaccination, 50-55% seroconversion to VV was observed in the volunteers twice immunized with the bivaccine (at an interval of 1 or 3-6 months). Cellular immunity to VV was low (0-20%). Double immunization of volunteers with the oral bivaccine under remote vaccination failed to produce the significant levels of humoral and cellular immune responses to hepatitis B markers. Recombinant VV was not recorded in any blood, saliva, and urine samples taken in the volunteers twice immunized with the bivaccine.

Nowadays there are certain facts which evidence the necessity of return to smallpox vaccination in Russia, especially concerning people who will be engaged in the liquidation of the nidi of this infection, should such appear. Smallpox virus is kept in laboratories of some countries; there is a real threat of biological terrorism; population immunity to smallpox infection is virtually absent. Considering the present situation in development and production of smallpox vaccines and remedies against vaccine-related complications, the tactics of population vaccination in Russia may vary. The main problems concerning return to smallpox vaccination in Russia are the following: there are no modern schemes (schedules) of smallpox immunization; there are no currently available and safe vaccines for primary immunization of adults; there are no preparations for prevention and treatment of vaccine-related complications. Thus, the priority areas are: development of effective and safe oral adult vaccines for primary immunization; production of human and heterologous immune globulins and their storage.

In the clinical trials of vaccine TEOVac in lower and reglamented doses under the conditions of remote vaccination, carried out on 11 volunteers, local reactions in the form of hyperemia, gingival edema (1 vaccinee), faucial hyperemia, enlargement of submaxillary lymph nodes (2 vaccinees) were registered in some of the vaccines; in one vaccinee systemic postvaccinal reaction of medium gravity was observed. Revaccination produced no negative effect on the hematological and biochemical characteristics of the blood, as well as on the urine characteristics. The study of the sensitizing vaccine to the antigens of the accumulation substrate (chick embryo), as well as its influence on the development of autoimmune reactions, revealed the absence of the allergic action of the preparation and its influence on autoimmune processes in the vaccines. The trial of the smallpox vaccine in tablets under the conditions of the primary immunization of adults was the topical and most promising trend in the improvement of smallpox vaccination, as the preparation TEOVac proved to be safe, in contrast to the traditional smallpox vaccine introduced by the scarification method, for both vaccines and nonimmunized persons having contacts with them.

On the basis of comparative experimental evaluation of specific features in the course of the vaccinal process after the immunization of laboratory animals with live smallpox vaccines, intended for oral use (in tablets) and for skin scarification was proposed. In experiments on rabbits, made with the use of virological and immunological methods, the counteraction of the elements constituting the vaccinal process was analyzed, the integral evaluation of its course was given, the greater safety of the oral preparation in comparison with the traditional vaccine for immunization by skin-scarification method were established. The conclusion was made that oral immunization was the safest immunization method under modern conditions and promising one for using live vaccines with population immunity being at a low level or absent.

The reactogenicity of the embryonic live recombinant variola and hepatitis B bivaccine as tablets (Revax-BT) as well as its safety and immunogenicity were evaluated in clinical trials made in volunteers who had previously immunized or not with variola vaccine. A preliminary conclusion was made on a lack of side effects and drug safety in primary vaccination and been revaccination with low and high doses. Primary immunization of volunteers and as bivaccination with high doses stimulated the most pronounced immune response to the vaccine virus versus such effect observed in immunization of volunteers with low vaccine doses. Humoral immune response to HBs was observed in 75% of volunteers of both groups after as bivaccination. Such response was most pronounced in examinees immunized with low vaccine doses versus those who received high bivaccine doses. At the same time, no protective levels of humoral immunity response to HBs Ag were observed in volunteers first vaccinated.

Results of comparative studies of tableted and epicutaneous live smallpox vaccines are presented. In experiments on rabbits by using histological, immunofluorescent, immunological and virological methods, higher safety and efficiency of the tableted vaccine than that of traditional smallpox epicutaneous vaccine were determined. The natural and physiological character of oral immunization was shown. The oral immunization was concluded to be a safe method of inoculation now and perspective for the use of recombinant vaccines based on vaccine virus in the absence of population immunity against smallpox.

The results of fundamental and applied investigations on the development and trial of the oral administration of smallpox vaccine and live recombinant smallpox-hepatitis vaccine (Revax VT) in tablets are summarized. In comparative experiments on animals (rabbits, monkeys and guinea pigs) and human immunization the oral smallpox vaccine in tablets was shown to ensure equal effectiveness and greater safety in comparison with traditional smallpox vaccine for skin application. The study confirmed the natural and physiological character of oral immunization as a result of direct contact of immunogen with the mucous membrane of the digestive tract--an essential immunocompetent organ of the lymphoid system. The conclusion was made that oral immunization was the safe and most promising method of immunization against smallpox under modern conditions.

Residual virulence of three vaccinia strains: Neurovaccine, L-IVP, and its recombinant Revacs-B expressing HBs and preS2 antigens of hepatitis B virus is compared. Insertion of HBs and preS2 antigens of hepatitis B virus in the genome of vaccinia virus strain L-IVP decreases its residual virulence and leads to a benign course of vaccinal reaction involving no deaths of rabbits, cotton rats, or guinea pigs. We may expect that recombinant vaccine Revacs B based on L-IVP strain will cause no postvaccinal complications under conditions of an appreciable decrease in population immunity to vaccinia virus.

Presents the methods of oral and enteral administration of vaccines in tablets. Describes the method of oral administration with a sponge and the technique of administering large and small tablets in the intestinal tract. Describes the specific features of administering tablets to mice, guinea pigs, rabbits, and monkeys.

High effectiveness of C.burnetii strain M-44 was confirmed in experimental studies on subcutaneously immunized guinea pigs ¿correction of pig] after their intratracheal infection with the virulent culture of the infective agent. The study revealed that the dose necessary for the enteral immunization of guinea pigs and monkeys was 10(4.8) -- 10(5.0) times less than that needed for the oral immunization of the animals. Live enteral vaccine obtained on the basis of this strain possessed sufficiently pronounced immunogenic and protective properties, protecting 75% of immunized monkeys from subcutaneous infection with C.burnetii virulent culture.

Oral and dermal administrations of vaccinia virus into rabbits, guinea pigs, and monkeys demonstrated a milder (without homeostasis disturbance) course of the vaccinal process with oral immunization, intensive immunity forming in minimal sensitization of the body was compared with dermal one. The results of revaccination in adults with oral smallpox vaccine and primary immunization in Ethiopia showed that oral immunization with vaccinia virus was safe, effective and lowly reactogenic. The comparative study of the preparation in remote revaccination (5 or more years later) proved its advantage over dermal vaccine. It consists in ecological safety (vaccinia virus excretion into the environment during 1 and 11 days, respectively, by 10-fold concentration reduction), reactogenicity (5 and 33% of common reactions, respectively) in the same immunogenicity.

The authors studied the penetration of variolo-vaccine virus through the mucosa of the small intestine of Macacus rhesus in enteral immunization, by immunofluorescent and virological methods. Fifteen minutes after the immunization the variolo-vaccine virus was revealed at the surface of the mucosal prismatic epithelium and in the t. mucosa propria within the cytoplasm of cells of the macrophage type. Dissemination of the process with detection of the variolo-vaccine virus in the blood, the lymph nodes, spleen and liver was determined within the range of 1 to 3 hours.