Content of A-, G- and M-class immunoglobulins in adults perorally immunized with a liver Sonne dysentery vaccine]

The authors studied the immunological shifts in the blood and saliva of 357 adults immunized with live enteral dysentery Sonne vaccine from a spontaneous mutant according to different schemes (1, 2, 3, 4 injections at 2--3-day intervals. The general level of IgA, IgG, and IgM increased during the immunization; there was also an elevation of the specific antibodies level of these classes in the blood of the persons vaccinated. Accretion was the greatest of IgA both in the blood and in saliva of the immunized persons; this pointed to a marked, chiefly local, immunological activity of the vaccine. As shown, during the immunization the rise and the changes in the antibody level of various immunoglobulin classes differed from such in dysentery infection; in the latter case, along with the IgA-antibodies there was a marked elevation of the IgG- and IgM-antibodies level. It is supposed that there was a possibility of a changed of a 4-time immunization scheme to-3-time one, with increase of intervals between the vaccine administration.     

Reactogenicity and immunologic activity of live enteric Sonne dysentery vaccine from a spontaneous mutant]

Live dysentery Sonne vaccine from a spontaneous mutant proved to be practically areactogenic and specifically harmless in oral immunization of children aged from 7 to 13 years, in doses of from 3 to 25 milliard live microbial cells and in single and triple immunization schemes. Weak reactions of the gastro-intestinal tract were noted with the same frequency (1.7%) in children immunized with the vaccine and in children given placebo (2.2%). There proved to be a significant increase in the serum of the immunized persons of the level of specific hemagglutinins, and also of the IgA-and IgM-titers in 82% of the persons vaccinated; they persisted at a high level for 2 months. The appearance of IgA-antibodies in high titres in the persons vaccinated orally pointed to a marked local and general immunological activity of the live dysentery Sonne vaccine from the spontaneous mutant processing the capacity to survive in the intestine of children for a long time.     

Immunologic properties of soluble shigella antigens]

Of the live Sh. Flexner 2a and Sonne soluble antigens containing glucide-lipoid-protein complex, characterized by low toxicity, a high yield of dry substances, and the capacity to induce immunity production in mice after subcutaneous and oral immunization, were obtained by salt extraction and physical disintegration. Local antigen application into eye mucosa of guinea pigs produced local resistance against homologous causative agents and also stimulated production of the highest level of specific antibodies at the site of administration in oral and conjunctival vaccination. A marked antigenic-immunological activity of soluble shigella antigens in local administration permits to refer them to the group of protective ones and to recommend their further study in the capacity of preparations for enteral vaccination against dysentery.     

Immunoglobulins and antibodies of various classes in children immunized with live oral Shigella sonnei vaccine from the spontaneous mutant]

The authors determined the immunoglobulin and specific antibodies level in the blood serum of 17 children aged from 7 to 10 years during the immunization with live dysentery Some vaccine. Mancini's test demonstrated the absence of any differences in the amount of IgA and IgG in children of the given age group and in adults before the immunization; in comparison with adults, IgM was increased in children. 14 to 20 days after the immunization in children there was a significant elevation of the IgG only, whereas in adults the immunoglobulin level of all the 3 classes increased significantly. The titres of specific antibodies of the IgA-, IgG-classes and of hemagglutinins before the immunization detected by Coombs' test failed to differ in children from the titres of antibodies of these classes in adults; the level of IgM antibodies was much greater in children than in adults. The changes and accumulation of antibodies of various classes in children and adults during the enteral immunization with live dysentery vaccine differed significantly: in children the vaccine stimulated the IgA- and the IgM-antibody synthesis, whereas adults responded to the immunization by increased production of all the 3 antibody classes. On the basis of the noted immunological shifts a conclusions was drawn on a marked local immunization activity of the live enteral Sonne dysentery vaccine from the spontaneous mutant in children.     

Study of the immunological effectiveness of the enteral vaccination of volunteers with detergent Sonne dysentery monovaccine]

The authors evaluated the immunological results of enteral and subcutaneous injection of detergent Sonne dysentery vaccine to volunteers (changes in homo- and heterologous antibodies in the blood and saliva recorded by means of common indirect hemagglutination test and that modified according to Coombs' test, and IgG, IgM, and IgA concentration recording. Both immunization methods induced specific antibody formation: enteral vaccination caused chiefly the accumulation of secretory antibodies of IgA class, and subcutaneous -- of serum antibodies belonging to IgG class. The supposed mechanisms determining the capacity of enteral administration of the antigen to provoke an immune response different from that caused by its subcutaneous injection are discussed.     

Jet method of administration of live brucella vaccine]

A good survival of brucellae in the organism with the development of a stable and prolonged immunity was noted in vaccination of guinea pigs with live brucella vaccine prepared from the Br. abortus strain 19-BA. Local reactions were weak, and no general reactions were observed. In using the jet method of vaccination with the injectors bpi-4 and bi-2 on a limited group of persons (194) the local and general untoward response was weak, but in immunological respect this method proved to be effective when the vaccine was administered in a dose of 2.5 x 10(8) of microbial cells. Jet method can be recommended for express vaccination against brucellosis.     

Evaluation of the immunological activity and safety of group B meningococcal vaccine prepared from a natural complex of specific polysaccharide and outer membrane proteins

Immunological activity and safety of group B meningococcal vaccine prepared from a natural complex of specific polysaccharide and outer membrane proteins were under study. The immunological safety of the vaccine was evaluated by the absence of antibodies to denaturated and native DNA (d-DNA and n-DNA). As shown with the use of the enzyme immunoassay (EIA), the administration of the vaccine did not induce antibody formation to d-DNA and n-DNA during the observation period. The titer of bactericidal antibodies in the immune bacteriolysis assay (IBA) to the vaccine strain B:2b:P1.2 after immunization increased four-fold and greater in 80% of the vaccinated persons. The significant increase of bactericidal antibodies to heterologous strains B:2a:P1.2 and B:15:P1.7 was registered in 20-30% of the vaccinees, respectively. A month after the repeated vaccination an increase in specific IgG antibodies to the complex antigen was found to occur according to EIA results. The use of RIB made it possible to evaluate the preventive activity of group B meningococcal vaccine as a whole and to suppose that the vaccine induced mainly type-specific response.     

Development of new types of chemical vaccine for prevention of intestinal infections and problems of their qualitative evaluation. III. Comparative study of immunologic characteristics of experimental antigenic preparations]

As a result of comparative study of the immunological properties and antigenic activity of thyphoid, paratyphoid A and B and Sonne and Flexner dysentery antigenic preparations obtained by various methods there was revealed a decreased toxicity of the experimental preparations of the Tashkent and Leningrad Institute of Vaccines and Sera (in comparison with the tryptic antigens) and a considerable advantages of the experimental thyphoid and paratyphoid antigenic preparations by their capacity to induce the H-antibody formation in the presence of the O-antigenic activity. The preparations of the Moscow Institute of Vaccines and Sera had increased toxicity. The detected advantages of the experimental antigenic preparations of the Tashkent and Leningrad Institute of Vaccines and Sera permitted to recommend the method used in their making to obtain new chemical vaccines against the intestinal infections.     

Live enteric typhoid vaccine consisting of a Vi-negative double-dependent mutant of S. typhi and a Vi-positive strain of Citrobacter]

The authors present experimental data on the study of the living enteral vaccine against the typhoid infection from the Vi-negative strain of salmonella with a double-dependence by streptomycin and purine, and from the Vi-positive strain -- citrobacter 5396/38. The method of immunoelectrophoretic analysis showed an indenticity of the O- and H-antigens of the doubledependent mutant with the O- and H-antigens of the typhoid strains of bacteria (Ty2-4446 and 5501). A sufficiently marked immunological reaction was revealed in the tests of antibody formation and in the study of the preventive activity of the sera of the immunized rabbits. The efficacy of the enteral immunization with the associated vaccine consisting of a doubledependent mutant of typhoid bacilli and the citrobacter strain in the doses tested (a 6-fold immunization) was demonstrated in experiments on albino mice. Association in one preparation of the cultures under study did not lead to any changes in the immunogenic properties of these strains. The cells of the mutant strain administered per os gave a positive culture (from the mouse organism) only in the course of the first 24 hours, in difference from the citrobacter strain which gave a positive culture in the course of 14 days.     

The immunization of adults against respiratory syncytial virus infection

The results of the comparative study of the immunological effectiveness of experimental samples of respiratory syncytial (RS) viral vaccine, prepared from a live attenuated strain and introduced in a single administration to young adults by the intranasal, intradermal and combined intranasal-intradermal) routes, are presented. The effectiveness of intranasal immunization was inversely related to the level of previously existing humoral (serum, secretory) antibodies. Intradermal immunization enhanced the frequency of the formation of serum antibodies in persons having had such antibodies before the introduction of RS vaccine. The most active formation of serum and secretory antibodies was ensured by the combined (intranasal-intradermal) method of the administration of live RS vaccine which proved to be particularly effective in persons having had antibodies in the blood and secretions prior to immunization.     

Evolution of poliovirus since introduction of attenuated vaccine.

Genetic marker tests were performed on 997 strains of poliovirus isolated from patients with neurological disease and from healthy people in England and Wales. Before the introduction of live attenuated vaccine most strains could multiply at raised temperatures. Now, however, many strains isolated from cases of poliomyelitis or from healthy persons with no known contact with vaccine cannot grow above 37 degrees C, and in this respect resemble the vaccine strains. The three serotypes are also much more evenly represented. Hence probably to a limited extent the vaccine-like strains have established themselves in the community.     

Comparative study of the safety, reactogenicity and antigenic activity of chemical and live brucellosis vaccines in a controlled epidemiological trial

The complex evaluation of the reactogenicity characteristics revealed that after immunization with chemical brucellosis vaccine systemic reactions observed in most of the vaccinees were mildly pronounced and local reactions, mildly and moderately pronounced, their duration not exceeding 48-72 hours. During 4 months after immunization the antigenic and immunogenic potency of chemical brucellosis vaccine was no different from that of live brucellosis vaccine; seropositive persons immunized with chemical and live brucellosis vaccines showed no statistically significant differences in the geometric mean of their antibody titers, as determined in a number of serological tests, for a year after immunization. The examination of the vaccinees 4 and 12 months after immunization revealed that the sensitizing activity of chemical brucellosis vaccine was, respectively, 12.2 and 2.5 times lower than the allergenic action of live brucellosis vaccine.     

Immune response following administration of multicomponent vaccine VP-4 in elderly patients

The dynamics of immunological characteristics after the administration of polycomponent vaccine B[symbol: see text]-4 to elderly persons, constituting a risk group with respect to acute respiratory diseases and exacerbations of chronic inflammatory diseases of respiratory organs, was studied. The nasal-oral administration of the vaccine induced immunological shifts in the systems of local and systemic immunity. The content of the populations of lymphocytes with markers CD3, CD4, CD16, CD20 was found to have positive dynamics. Considerable shifts in the system of local immunity were registered: the content of sIgA and IgA in the saliva greatly increased; in addition, an increase in the titers of antibodies to Staphylococcus aureus, Klebsiella pneumoniae and Escherichia coli was observed in persons with initially low titers.     

Enterotoxic activity of live cultures of Sonne dysentery microbes and formation of enterotoxin in vivo]

The great majority of virulent Sonne dysentery bacillus cultures caused an accumulation of the fluid in the lumen of the isolated segment of the rabbit small intestine containing a great amount of mucus and sometimes of the blood as well; the segment mucosa was hyperemic and had punctate hemorrhages. Avirulent microbial cultures as a rule caused no exudation in the intestinal lumen. Sterile and concentrated contents of the intestinal loops responding to the centrated contents of the intestinal loops responding to the administration of the virulent culture of Sonne bacillus or a toxigenic strain of Grigoriev-Shiga dysentery bacillus caused a positive response in other rabbits. The character of the exudate and the changes in the mucosa failed to differ from such following the administration of live cultures.     

Lactic acid bacteria — promising vaccine vectors: possibilities,limitations, doubts

Gram‐positive, nonpathogenic lactic acid bacteria (LAB) are considered to be promising candidates for the development of novel, safe production and delivery systems of heterologous proteins. Recombinant LAB strains were shown to elicit specific systemic and mucosal immune responses against selected antigens. For this reason, this group of bacteria is considered as a potential replacement of classical, often pathogenic, attenuated microbial carriers. Mucosal administration of recombinant LAB, especially via the best explored and universal oral route, offers many advantages in comparison to systemic inoculation, and is attractive from the immunological and practical point of view. Research aimed at designing efficient, mucosally applied vaccines in combination with improved immunization efficiency, monitoring of in vivo antigen production, determination of optimal dose for vaccination, strain selection and characterization is a priority in modern vaccinology. This paper summarizes and organizes the available knowledge on the application of LAB as live oral vaccine vectors. It constitutes a valuable source of general information for researchers interested in mucosal vaccine development and constructing LAB strains with vaccine potential.     

Efficacy of the per os immunization and reimmunization of man with staphylococcal anatoxin]

By double immunization of 72 persons and single reimmunization of 38 persons per os with tablets containing 100 BU of purified concentrated staphylococcus toxoid (PCST) it was revealed that this immunization was harmless and the immunological response was adequate. The tablets were intended for application through the oral mucosa (oral) or the intestinal tract (enteral); the immunological response depended on the dose of the preparation and the scheme of administration. A high sensitization of healthy persons examined to staphylococcus was found. There was a tendency to reduction of hypersensitivity after the immunization with staphylococcus toxoid (examination in 6 months) and activation of reactions after the antigen administration (examination in 14 days).     

Vaccination activity of live influenza vaccine in different seasons of the year

Reactogenicity, immunogenicity and viability of the vaccine virus were studied during vaccination of adults with live allantoic influenza vaccines of the types A (H1N1), A (H3N2) and B in different seasons of the year. Seasonal oscillations of reactogenicity of the vaccines (minimum in summer, maximum in winter) were demonstrated. A decrease in the re-isolation rate of vaccine viruses and in their content in the secretions of the upper respiratory passages was observed in summer. Seasonal oscillations of immunogenicity of the commercial live allantoic influenza vaccine with a marked reduction in its activity in summer were established. The administration of moderately attenuated influenza vaccine viruses in summer results in the production of antibodies up to the level observed in other seasons of the year. Theoretical problems and practical aspects of seasonal oscillations of vaccination activity of live influenza vaccines were studied in connection with the necessity of investigation new vaccine strains in varying seasons of the year.     

Indicators of spontaneous and stimulated nitroblue tetrazole test of polymorphous-nuclear leucocytes in acute dysentery patients

140 healthy individuals and 93 sick with acute dysentery were subjected to an examination by spontaneous and by bacterial preparations stimulated reaction with nitroblue tetrazole (NBT test). Indicators in healthy persons were normal in the spontaneous, and increased in the NBT test, stimulated by bacterial preparations. Indicators of the spontaneous NBT test in patients with acute dysentery were raised with a maximum in the period of early convalescence. Stimulation by a live shigella culture--the dysentery vaccine--revealed by means of Sonne diagnostic high, and when endotoxin from Serratia marcescens and dysenterin was used as an inductor, mild indicators of NBT test activity. When a polyvalent agglutinating dysentery serum was used as a stimulator, the activity increased considerably, and a simultaneous use of serum and vaccine had an inhibiting effect on the indicators of the stimulated NBT test. The obtained results testify the sufficient high reserve possibilities of leucocytes towards complete phagocytosis and the efficiency of the NBT test, stimulated by bacterial preparations for the study of functional and metabolic activity of leucocytes in the process of acute bacterial dysentery.     

An index of blood neutrophil injury in man and animals immunized with live anthrax vaccine]

The authors present the results of study of the blood neutrophil injury in guinea pigs, rabbits, monkeys, and also humans inoculated subcutaneously with live anthrax vaccine. Along with intradermal test with anthraxin, the mentioned test is suggested to assess the immunological status of persons immunized with anthrax vaccine.     

Efficacy of production of reassortant of epidemic strains and cold-adapted influenza viruses in chicken embryo and MDCK cells

Reassortant strains for modern live influenza vaccines are prepared using growing chicken embryos. It is very important to switch manufacture of influenza vaccines from chicken embryos to cell cultures, especially due to the threat of future pandemic, when there will be need of big quantities of vaccine for immunization of all age groups. Efficacy of production of reassortant strains with 6:2 vaccine formulation of genome (6 internal genes from the donor of attenuation and 2 genes coding external antigens--hemagglutinin and neuraminidase--from epidemic strain) in MDCK cell culture, using standard techniques employed for production of the vaccine in chicken embryos, was studied. It was shown that yield frequency of aforementioned reassortants of influenza A viruses did not exceed 5.7% whereas in chicken embryos vaccine 6:2 reassortants were isolated with frequency of 4%. For influenza B viruses, yield of 6:2 reassortants in growing chicken embryos exceeded 67% whereas in MDCK cell culture we were unable to produce clones with required genome composition. Thus, existing method while effective for production of vaccine reassortants in chicken embryos is low effective for isolation of 6:2 reassortants in MDCK cell culture. Fundamentally new techniques are needed for production of reassortant strains for live influenza vaccine in cell culture.