Protective activity of a cell-free Klebsiella vaccine in infection in mice caused by Streptococcus pneumoniae serotypes

The capacity of dried Klebsiella cell-free vaccine, obtained from strain No. 204 by the disintegration of microbial mass with hydroxylamine, for protecting mice from pneumococcal infection caused by S. pneumoniae, serotypes 3, 4 and 9N, has been studied. Klebsiella vaccine has been found to possess immunostimulating potency with respect to the S. pneumoniae serotypes under study. On day 5 this potency is manifested to a greater extent than 24 hours after immunization. The combination of Klebsiella vaccine with Proteus vulgaris, Staphylococcus aureus and Escherichia coli K-100 antigens enhances the stimulation of nonspecific resistance.     

Possible use of a concentrated vaccine against tick-borne encephalitis for immunizing donors to obtain specific immunoglobulin

The immunization of donors with dried, purified, inactivated and concentrated cell-culture tick-borne encephalitis vaccine, produced at the Institute of Poliomyelitis and Viral Encephalitides in Moscow, has been carried out with the aim of obtaining immune raw material for the production of specific donor immunoglobulin. The high immunogenic potency and low reactogenicity of the vaccine, introduced in 2 injections at an interval of 6 months, have been confirmed. Immunization in 2 injections has proved to be as effective as that achieved by 3 injections. The expediency of the immunization of regularly bled donors has been established: hemagglutinin titers in these donors have been found to be significantly higher than in a group of persons never bled before. The optimum time for taking blood has been determined: 3 weeks for regularly bled donors and 2 weeks for donors bled for the first time. Blood may be taken again 2 months after the first bleeding without booster immunization and 2 weeks after the third injection of the vaccine.     

Production and study of the properties of a polyvalent corpuscular Pseudomonas aeruginosa vaccine. IV. The effect of immunization with Pseudomonas aeruginosa vaccine on the immune status of volunteer donors

The influence of immunization with P. aeruginosa vaccine on the immune status of volunteer donors has been studied. Immunization with P. aeruginosa vaccine in doses of 0.5-0.5-1.0 ml at intervals of 7 days has been found to lead to the 13-fold increase of the titer of specific antibodies, lasting for 3-4 months, which ensures the possibility of obtaining anti-P. aeruginosa hyperimmune plasma with standard titers. The injection of P. aeruginosa vaccine to donors leads to the activation of humoral immunity simultaneously with the increase of the absolute and relative number of rosette-forming B-lymphocytes without essential changes in the amount of rosette-forming T-lymphocytes.     

Protective effect of the aerosol immunization of mice with the polycomponent vaccine Immunovac VP-4 after the challenge of the animals with Klebsiella pneumoniae virulent strain

Used four schemes of the administration of the preparation with different time of the exposition of the animals in an aerosol chamber were tested with their subsequent intraperitoneal challenge with K. pneumoniae virulent strain K16. Irrespective of the number of immunization courses, the administration of the preparation made at intervals of 1 day, or daily, did not ensure any protective effect, but only led to an insignificant increase in their survival time in comparison with nonimmunized animals. After intervals between immunizations were increased to 3 days the protective effect of aerosol immumization was obtained (the survival rate was 65-80 % and considerably differed from that of the controls). The protective effect of aerosol immunization thus obtained was comparable with the effectiveness immunization made in a single subcutaneous injection. Aerosol immunization resulted in low antibody titers to the antigens contained in the vaccine, while after a single subcutaneous injection high antibody titers to Klebsiella and Proteus antigens were detected. The antigen-stimulated blast transformation of spleen lymphocytes in mice subjected to aerosol immunizations in 5 exposures was high. After subcutaneous immunization significant changes in such characteristics were detected on day 15. The data thus obtained were indicative of good prospects in the development Immunovac VP-4 as the medicinal form intended for use in aerosols.     

Immunomorphologic study of experimental enteric anc combined vaccination against cholera]

As a result of the enteral and combined subcutaneous-enteral immunization of adult rabbits with cholerogen toxoid and the specific fraction of chemical cholera vaccine in tablets immunological transformation occurred in the organism and a "protective" barrier consisting of antibody-containing cells was formed in the intestine on days 3-5. The combined method of immunization with cholera vaccine proved to be essentially as effective as enteral immunization in 2 administrations.     

MVA-Based H5N1 Vaccine Affords Cross-Clade Protection in Mice against Influenza A/H5N1 Viruses at Low Doses and after Single Immunization

Human infections with highly pathogenic avian influenza viruses of the H5N1 subtype, frequently reported since 2003, result in high morbidity and mortality. It is feared that these viruses become pandemic, therefore the development of safe and effective vaccines is desirable. MVA-based H5N1 vaccines already proved to be effective when two immunizations with high doses were used. Dose-sparing strategies would increase the number of people that can be vaccinated when the amount of vaccine preparations that can be produced is limited. Furthermore, protective immunity is induced ideally after a single immunization. Therefore the minimal requirements for induction of protective immunity with a MVA-based H5N1 vaccine were assessed in mice. To this end, mice were vaccinated once or twice with descending doses of a recombinant MVA expressing the HA gene of influenza virus A/Vietnam/1194/04. The protective efficacy was determined after challenge infection with the homologous clade 1 virus and a heterologous virus derived from clade 2.1, A/Indonesia/5/05 by assessing weight loss, virus replication and histopathological changes. It was concluded that MVA-based vaccines allowed significant dose-sparing and afford cross-clade protection, also after a single immunization, which are favorable properties for an H5N1 vaccine candidate.     

Experimentally determined safety and immunological activity of vaccine based on antigens isolated from Pseudomonas aeruginosa in medium K-4

The safety and immunological activity of P. aeruginosa vaccine were experimentally evaluated. The vaccine was prepared on the basis of the antigens of P. aeruginosa extracellular slime which was accumulated in medium K-4, obtained with the use of original technology. The immunization of animals with P. aeruginosa vaccine induced the synthesis of antibodies. The introduction of the vaccine in 2 or 3 injections resulted in a high level of antibody formation, differing with the use of various strains. Hyperimmune sera, obtained by the multiple immunization of rabbits with P. aeruginosa vaccine, ensured high protection of mice from P. aeruginosa infection. The vaccine proved to be safe when evaluated in experiments of acute and chronic toxicity, made on laboratory animals.     

Preventive properties of the blood sera from persons vaccinated with a Proteus vaccine made from soluble antigen complexes

In experiments of the passive protection of mice the protective properties of sera obtained from humans before and after their immunization with Proteus vaccine used as a monopreparation or in combination with staphylococcal toxoid and/or pyoimmunogen were studied. When introduced in a single subcutaneous injection, Proteus vaccine prepared from soluble antigenic complexes ensured an increase in the protective properties of sera. The second injection of the vaccine essentially enhanced the protective potency of the sera of the immunized donors. The therapeutic injection of Proteus vaccine ensured the essential increase of the protective properties of the sera. This increase could be experimentally detected within at least 25-30 days from the beginning of immunization. The immunization of volunteers with Proteus vaccine in combination with pyoimmunogen and adsorbed staphylococcal toxoid ensured the maximum increase of the protective properties of their sera.     

Age at Mycobacterium bovis BCG Priming Has Limited Impact on Anti-Tuberculosis Immunity Boosted by Respiratory Mucosal AdHu5Ag85A Immunization in a Murine Model

Tuberculosis (TB) remains a global pandemic despite the use of Bacillus Calmette-Guérin (BCG) vaccine, partly because BCG fails to effectively control adult pulmonary TB. The introduction of novel boost vaccines such as the human Adenovirus 5-vectored AdHu5Ag85A could improve and prolong the protective immunity of BCG immunization. Age at which BCG immunization is implemented varies greatly worldwide, and research is ongoing to discover the optimal stage during childhood to administer the vaccine, as well as when to boost the immune response with potential novel vaccines. Using a murine model of subcutaneous BCG immunization followed by intranasal AdHu5Ag85A boosting, we investigated the impact of age at BCG immunization on protective efficacy of BCG prime and AdHu5Ag85A boost immunization-mediated protection. Our results showed that age at parenteral BCG priming has limited impact on the efficacy of BCG prime-AdHu5Ag85A respiratory mucosal boost immunization-enhanced protection. However, when BCG immunization was delayed until the maturity of the immune system, longer sustained memory T cells were generated and resulted in enhanced boosting effect on T cells of AdHu5Ag85A respiratory mucosal immunization. Our findings hold implications for the design of new TB immunization protocols for humans.     

Prophylactic immunization against experimental leishmaniasis. V. Mechanism of the anti-protective blocking effect induced by subcutaneous immunization against Leishmania major infection

The responsiveness of BALB/c mice to protective i.v. immunization with 150,000-rad irradiated or heat-killed Leishmania major promastigotes can be totally suppressed by prior subcutaneous (s.c.) injection of the same "vaccine." Induction of this effect is leishmania specific for although prevention of protection against L. major infection can be obtained with either homologous or Leishmania donovani promastigotes, it does not follow s.c. administration of an immunogenic Trypanosoma cruzi epimastigote preparation. Multiple s.c. injections of irradiated L. major promastigotes do not inhibit the subsequent antibody response of any major isotype to i.v. immunization, but rather induce some priming. The same s.c. injections induced delayed-type hypersensitivity (DTH) reactivity that could be transferred locally or systemically, although it was weaker than in mice with cured infections. Parallel cell-mediated immunity (CMI) responses were also reflected in vitro in specific lymphocyte transformation assays. Despite this evidence of a DTH/helper type of T cell response, transfer of 5 X 10(7) viable T cell-enriched spleen cells from 4 X s.c. immunized donors to normal recipients completely abrogated the protective response to i.v. immunization. Conversely, T cell-depleted (anti-Thy-1.2 + C treated) cells were without effect. The inhibitory T cells were defined by monoclonal antibody pretreatment as possessing an Lyt-1+2-,L3T4+ phenotype. T cells from s.c. immunized donors were also shown, by mixed transfer experiments, to counteract completely the protective effect of T cells from i.v. immunized donors in 550-rad irradiated recipients. They were as potent as suppressor T cells from donors with progressive disease both in this capacity and in abrogating the prophylactic effect of sublethal irradiation itself. The similarities and differences between suppressor and immune effector T cells induced by s.c. or i.v. immunization and those arising in response to leishmanial infection itself are discussed.     

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.     

Single immunization with MF59-adjuvanted inactivated whole-virion H7N9 influenza vaccine provides early protection against H7N9 virus challenge in mice

H7N9 influenza infection in humans would result in severe respiratory illness. Vaccination is the best way to prevent influenza virus. In this paper, we investigated the effect of early protection provided by inactivated whole-virion H7N9 influenza vaccine in a mouse model.Mice were immunized intramuscularly once with different doses of inactivated whole-virion H7N9 influenza vaccine alone or in combination with MF59 adjuvant. Specific IgM and IgG antibody titers in sera of mice were detected by ELISA 3, 5 and 7days after immunization. To evaluate the early protection provided by the vaccine, mice were challenged with lethal dose (40LD₅₀) of homologous virus 3, 5 and 7 days after immunization respectively. The survival rate and body weight change of mice during 21 days after challenge and the residual lung virus titer on 3rd day after challenge were determined. The results demonstrated that mice could obtain effective protection 3 days after immunization with the vaccine at a high dose, and 5–7 days after immunization even at a low dose. Thus early immune responses induced by inactivated whole-virion H7N9 vaccine could provide effective protection.     

The dynamics of the T-lymphocyte subpopulations and the peroxidase activity of the neutrophils in children immunized with a live mumps vaccine

The amount of T-helpers and T-suppressors and the T-helper/T-suppressor ratio were determined in 30 practically healthy children aged 1.5-2 years, immunized with live parotitis vaccine prepared from strain -3. One immunization dose of the vaccine contained 7,950 HADU50. In all children peroxidase activity in the cytoplasm of neutrophils was studied. This investigation revealed that in all examined children the formation of immune response to immunization with live parotitis vaccine was accompanied by the development of an imbalance of immunoregulatory T-cell subpopulations and by functional changes in neutrophils, characterized by the inhibition of peroxidase activity. The changes revealed in this study were most pronounced in children with a high level of antibody formation.     

Vaccina treatment in some hospital infections.

Phenol-treated vaccine was prepared from the usual hospital strains and patients with colorectal cancer were immunized intramuscularly 7-10 days prior to the operation. The efficiency of the vaccine treatment was judged by the incidence of wound infections. The best results were obtained in patients whose previously estimated immunoreactivity was strong or normal. Immunospecificity could not be detected in the above treatment. The frequent and inappropriate use of antibiotics in hospitals increases the number of resistant hospital bacterial strains. Apart from Staphylococci and Streptococci, different Gram-negatives--such as Klebsiella, Serratia, Pseudomonas, Proteus and E. coli strains--have been found in the hospitals and in the patients. Due to the resistance, it is difficult to find antibiotics against them. This fact puts forward the possibility of immunization especially by vaccination.     

Assessment of the effectiveness of different methoods of immunization with live plague vaccine EB in aerosol infections]

The work deals with the results of the comparative evaluation of the effectiveness of vaccines developed at the Sanitary Research Institute (Zagorsk) and the Mechnikov Research Institute for Vaccines and Sera (Moscow), as well as two methods of immunization against plague, by inhalation and subcutaneous injection, under the conditions of aerosol infection. The immunogenic effectiveness of both vaccines, when evaluated in terms of LD50, was shown to be approximately the same, but the animals immunized by the inhalation method with the vaccine developed at the Sanitary Research Institute proved to be less susceptible to infection than those immunized with the vaccine developed at the Mechnikov Research Institute for Vaccines and Sera in Moscow. After immunization by the inhalation method the vaccine developed at the Sanitary Research Institute rendered more effective protection (3- to 4-fold) against aerosol infection than after immunization by subcutaneous injection. The animals immunized by the inhalation method proved to be capable of surviving plague in the primary pneumonic form.     

Experimental model ofKlebsiella infection in mice for studies on mechanisms of local immunity of the respiratory tract

An experimental model in white mice, infected with a mildly virulent strain ofKlebsiella pneumoniae, was elaboratored for studies on local immunity of the respiratory tract. Instillation of klebsiella into the supralaryngeal space of anaesthetised animals proved to be more suitable than the commonly used method of intranasal infection. The strain administered by the supralaryngeal route, persisted in the lungs of most mice at approximately equal level 1 d after infection, in some animals it could be demonstrated even after 2–3 d. Using this model (based on various rates of lung clearance), one can demonstrate faster elimination of klebsiella after a local (supralaryngeal) than systemic (intraperitoneal) immunization with a heat-inactivated vaccine, prepared from a homologous strain ofK. pneumoniae.     

The improvement of immunobiological preparations against leptospirosis. An experimental study of a new concentrated purified vaccine against icterohemorrhagic leptospirosis for human immunization

The findings of the study of immunological structure of the population in regions endemic for leptospirosis indicate that the immune status of humans makes it impossible to obtain titrated blood sera for the preparation of antileptospirosis immunoglobulin. The data obtained in the study of the immunobiological properties of a new concentrated vaccine against icterohemorrhagic leptospirosis show the possibility of using this vaccine for the immunization of donors with the aim of obtaining blood sera to be used as raw material for the production of immunobiological preparations.     

Characteristics of the clinical and immunologic safety of inactivated influenza vaccines in children undergoing multiple immunizations

In a strictly controlled epidemiological trial on 12,643 school children aged 11-14 years the reactogenic properties and safety of killed influenza chromatographic vaccine under the conditions of multiple immunization were studied. A single immunization dose of the vaccine (0.2 ml) contained the hemagglutinins of influenza viruses A/Philippines/82 (H3N3) and A/Kiev/59/79 (H1N1), 3.5 micrograms each. The preparation was introduced by means of a jet injector. The vaccine was shown to be clinically and immunologically safe under the conditions of the regular multiple immunization of children over the period of 4 years.