Evaluation of the vaccinal process in skin-scarification and oral immunization of rabbits with live smallpox vaccines

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.     

Results of basic and applied investigations on oral immunization 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.     

Immunogenesis and nonspecific factors of natural resistance. XI. Further study of the depression mechanism of humoral reactions of natural immunity during the vaccinal process]

The mechanisms of depression of humoral reactions of natural immunity under the effect of vaccination were studied further. Experiments were carried out on albino rats tolerant to the horse serum protein. Administration of the antigen to the tolerant animals failed to cause formation of antibodies or to influence humoral factors of natural immunity. As to rats not immunized earlier, complement-fixing antibodies were revealed from the 7th to the 21st days after the administration of horse serum; simultaneously there was seen depression of the humoral mechanisms of natural resistance. The results obtained confirmed the hypothesis stating that there existed competitive relations between the specific and nonspecific immunological reaction in the fight for plastic provision of the corresponding reactions.     

Immunocytochemical indices of the measles vaccinal process

To study the immune responsiveness of children in the measles vaccinal process, the cytochemical methods for the identification of immunocompetent cells have been used. The investigations have been made in children aged 1.5-4 years, immunized with live measles vaccine prepared from strain l-16. The results of these investigations indicate that the development of specific antiviral postvaccinal immunity is characterized by transitory changes in the populations of T-, B- and O-lymphocytes; such changes are accompanied by not only quantitative, but also qualitative changes of individual populations.     

The dynamics of antibody formation to a vaccinal strain of Francisella tularensis in different immunization regimens

The use of different schemes of albino mice immunization either by living or by killed preparations of the vaccine strain of Francisella tularensis when obtaining monoclonal antibodies to the tularemia microbe made it possible to reveal definite regularities in the dynamics of antibody formation. The highest titres of antibodies in sera of animals-donors of splenocytes were obtained during the daily (for 3 days) intraperitoneal immunization of mice with living vaccine or with its thrice administration to the spleen thrice with the interval of 10 days. Revaccination against a background of high titres of antibodies decreased their quantity in blood serum of mice, while that against a background of low titres increased them.     

Protective immunization against group B meningococci using anti-idiotypic mimics of the capsular polysaccharide

Use of the serogroup B meningococcal capsular polysaccharide (MenB CP) as a vaccine is hampered by the presence of epitopes that cross-react with human polysialic acid. As non-cross-reactive, protective capsular epitopes have also been described, we set out to develop protein mimics of one of such epitopes using as a template a highly protective mAb (mAb Seam 3) raised against a chemically modified form of the MenB CP (N-Pr MenB CP). Using phage display, anti-idiotypic single-chain Ab fragments (scFvs) were obtained from spleen cells of mice immunized with the Seam 3 mAb. Two Seam 3-specific scFvs competed with N-Pr MenB CP for binding to either mAb Seam 3 or rabbit Abs present in typing sera. Moreover, in mice and rabbits the scFvs elicited the production of Abs reacting with both N-Pr MenB CP and whole meningococci, but not with human polysialic acid. These scFv-induced Ab responses were boostable and of the Th1 type, as shown by a predominance of IgG2a. In addition, passive immunization with sera from scFv-immunized animals partially protected neonatal mice from experimental infection with group B meningococci. In conclusion, we have produced anti-idiotypic scFvs that mimic a protective MenB CP epitope and may be useful in the development of an alternative group B meningococcal vaccine.     

The natural silk spinning process. A nucleation-dependent aggregation mechanism?

The spinning mechanism of natural silk has been an open issue. In this study, both the conformation transition from random coil to beta sheet and the beta sheet aggregation growth of silk fibroin are identified in the B. mori regenerated silk fibroin aqueous solution by circular dichroism (CD) spectroscopy. A nucleation-dependent aggregation mechanism, similar to that found in prion protein, amyloid beta (Abeta) protein, and alpha-synuclein protein with the conformation transition from a soluble protein to a neurotoxic, insoluble beta sheet containing aggregate, is a novel suggestion for the silk spinning process. We present evidence that two steps are involved in this mechanism: (a) nucleation, a rate-limiting step involving the conversion of the soluble random coil to insoluble beta sheet and subsequently a series of thermodynamically unfavorable association of beta sheet unit, i.e. the formation of a nucleus or seed; (b) once the nucleus forms, further growth of the beta sheet unit becomes thermodynamically favorable, resulting a rapid extension of beta sheet aggregation. The aggregation growth follows a first order kinetic process with respect to the random coil fibroin concentration. The increase of temperature accelerates the beta sheet aggregation growth if the beta sheet seed is introduced into the random coil fibroin solution. This work enhances our understanding of the natural silk spinning process in vivo.     

The role of delayed hypersensitivity in the development of an experimental dysentery infection and vaccinal process

The results of experiments, indicating the development of cell-mediated delayed hypersensitivity (DH) skin reaction, its dependence on the virulence of Shigella flexneri 2a, the dose and the character of the antigen used for testing the reaction, are presented. One of the immunologically active components of S. flexneri virulent strain 2a No. 516 is a biologically active thermolabile factor detected in filtrate and supernatant fluid. These data suggest that the immunosuppressive action of the virulent strain is probably linked with the function of T-suppressors affecting the reaction at the period of its development (the induction phase). S. flexneri avirulent strain produced no such effect, developing DH being seemingly sufficient for activating T-cell-mediated immune response.     

Immunologic reactivity of children with allergic diseases during the measles vaccinal process

Children immunized with live measles vaccine, especially those immunized at the period of short-term remission and having had systemic or allergic reactions after the administration of the vaccine, have been found to develop more pronounced changes in the content of IgE. A high concentration of IgE is supposed to inhibit phasic changes in the content of IgM and IgG, which negatively affects the intensity of the formation of specific immunity.     

Specific features of diphtheria vaccinal process in children with rheumatic diseases

Clinical and immunological examination of 55 children aged 6-15 years with rheumatic diseases, immunized against diphtheria, was carried out. All children were immunized at the stage of clinical and laboratory remission and in some cases while undergoing a prolonged course of cytostatic therapy or therapy with nonsteroid anti-inflammatory remedies. This examination demonstrated that in the overwhelming majority of children with rheumatic diseases the diphtheria vaccinal process took an asymptomatic course and had no influence on the course of the main disease. Specific features, characteristic of the immune status of this group of children, were established. In the course of the vaccinal process the restoration of the initially inhibited characteristics (the production of TNF-alpha and IL-2) to normal values were shown to occur, which was indicative of the fact that the reserve capacities of immunocompetent cells were retained in these patients. This study also revealed that immunization of children with rheumatic diseases with adsorbed DT and D toxoids with reduced antigen content was not excessive antigenic stimulation for such children, as it did not lead to immunopathological shifts, but induced transient phase changes in immunological characteristics, similar to those in healthy children. Protective levels of antibodies to diphtheria were shown to retain for a long time with considerable prolongation of intervals between booster injections. The simultaneous course of immunosuppressive maintenance therapy in the average dosage used for the corresponding age group did not inhibit the production of protective antibodies.