Immunological response of three mouse strains to typhoid vaccine and Vi antigen

Vi-agglutinin, active cutaneous anaphylaxis and protective responses (ed(50)) of three mouse strains (CFW, NIH, and Balb/cAnN) to acetone-inactivated typhoid vaccine and soluble Vi antigen were compared. Seven days after immunization with either typhoid vaccine or Vi antigen the three strains of mice differed with respect to Vi-antibody titers. Significant differences were observed in the protective responses. Each mouse strain was significantly better protected by the intraperitoneal than by subcutaneous route of immunization. Active cutaneous anaphylaxis was more pronounced in showing strain differences in response to Vi antigen. The serological responses to Vi antigen of the strains of mice did not correlate with their protective response.     

Increasing the radioprotective therapeutic efficacy of typhoid vaccine using sexta-anatoxin in combination with the antimetabolite methotrexate]

A typhoid vaccine with sexta-anatoxin delivered to mice 4.5-5 h after gamma-irradiation has a pronounced therapeutic effect: survival rate is 42% with radiation dose of 8.2 Gy (LD85/30) and 19% with radiation dose of 8.7 Gy (LD95/30). The vaccine of 2.5 and 5 mg/kg combined with methotrexate has a more pronounced therapeutic effect increasing the survival rate up to 65% (LD85/30) and up to 35-40% (LD95/30).     

Change in the plasmocytic reaction of immunized animals during the use of antibiotics]

The effect of tetracycline and tetraolean on the shifts in the plasma-cell elements was studied experimentally on male albino rats of Wister line and rabbits immunized with foreign erythrocytes and typhoid fever vaccine respectively. It was noted that prolonged use of the antibiotics for 10 to 12 days inhibited proliferation of the plasmic cells, the inhibitory effect of tetracycline being more pronounced. At the same time an inhibitory effect of the antibiotics on the antibody formation in the animals was found in the experiments.     

伤寒Vi多糖菌苗多糖含量及分子大小测定试验

伤寒Ｖｉ多糖菌苗是我国新近研制成功的一种多糖菌苗。为了严格控制该制品的质量,经反复试验,建立了多糖含量和分子大小的测定方法。本文报导了（１）用火箭电泳法测定伤寒Ｖｉ多糖菌苗多糖含量。经对不同实验条件进行比较,选择出较为理想的条件。用该法测定８批样品。结果均符合规程要求。对其中５批样品进行６次重复试验表明,该法的重复性好,操作简单,是测定多糖含量较为理想的方法。（２）用琼脂糖柱层析法对２８批伤寒Ｖｉ多糖菌苗的分子大小进行测定。对用该法所得柱层析收集液分别用Ｈｅｓｔｒｉｎ法和２０６ｎｍ扫描法测定其多糖回收率,对测定结果进行比较。结果表明,两种方法的测定结果无显著性差异（Ｐ＞０．０１）,而且重复性均好。可根据实验室条件选择测定方法。     

Measles encephalitis; a successful method of treatment with typhoid vaccine

During a 12-year period 50 patients with measles encephalitis were treated with typhoid vaccine-45 of them not until they were in a vegetative state. There were no deaths in the treated cases. All except one were clinically normal after treatment was ended. Late in the series it became apparent that after the clinical normal is attained and the electroencephalogram becomes normal, treatment should still be continued until the cortex has been "challenged" repeatedly and the electroencephalogram shown to remain normal. The "shock" element in the treatment with typhoid vaccine was prevented by anticipating and circumventing the unfavorable reactions to the vaccine. It may take 20 to 50 treatments or more with typhoid vaccine to return a patient to normality. Each individual is different and responds in a different period of time.     

Further research on an experimental justification for the emergency prophylaxis of typhoid]

Experiments were conducted on mice. A possibility was demonstrated of express prophylaxis of typhoid fever by subcutanoues injection of the vaccine and by oral administration of sodium nucleinate, of lowering the dose by half and replacement of revaccination by sodium nucleinate alone. An increase in the titre of typhoid agglutinins and of preventive activity of the blood serum was revealed on volunteers.     

MEASLES ENCEPHALITIS—A Successful Method of Treatment with Typhoid Vaccine

During a 12-year period 50 patients with measles encephalitis were treated with typhoid vaccine—45 of them not until they were in a vegetative state. There were no deaths in the treated cases. All except one were clinically normal after treatment was ended. Late in the series it became apparent that after the clinical normal is attained and the electroencephalogram becomes normal, treatment should still be continued until the cortex has been “challenged” repeatedly and the electroencephalogram shown to remain normal.The “shock” element in the treatment with typhoid vaccine was prevented by anticipating and circumventing the unfavorable reactions to the vaccine.It may take 20 to 50 treatments or more with typhoid vaccine to return a patient to normality. Each individual is different and responds in a different period of time.     

Assessment of effectivity of oral killed typhoid and paratyphoid B vaccines and aerosol chemical typhoid vaccine in controlled field trials.

A total of 3 controlled field trials were carried out. One of them (1963) showed that aerosol chemical typhoid vaccine did not protect vaccinated subjects from the disease. Two other tests (1964 and 1965) assessing the effectivity of killed orally administered typhoid vaccine revealed a short term (up to 3 months) protective effect expressed by an effectivity coefficient of 45%, fiducial limits being 8-70%. In the assessment of oral paratyphoid B vaccine, the difference in morbidity in the experimental and control groups was statistically insignificant due to a small number of cases of disease.     

伤寒Vi多糖菌苗接种反应观察

本文报告了对我国首次成功的伤寒Ｖｉ多糖菌苗进行人体接种反应观察结果,接种对象为２０至５４岁无伤寒病史,近年无伤寒菌苗接种史的健康人,共６０名,以完全随机的方法分为两组,实验组注射３０μｇＶｉ多糖菌苗,对照组注射Ｖｉ多糖菌苗的稀释液。其结果３０名Ｖｉ多糖菌苗接种者注射后体温无中重反应发生,局部红肿仅有１例中反应。注射后对血压、心律没有影响。红细胞计数,白细胞计数均在正常范围,与接种前相比,无显著差异     

25 Years after Vi Typhoid Vaccine Efficacy Study,Typhoid Affects Significant Number of Population in Nepal

Salmonella Typhi, first isolated in 1884, results in infection of the intestines and can end in death and disability. Due to serious adverse events post vaccination, whole cell killed vaccines have been replaced with new generation vaccines. The efficacy of Vi polysaccharide (ViPS) vaccine, a new generation, single-dose intramuscular typhoid vaccine was assessed in Nepal in 1987. However, despite the availability of ViPS vaccine for more than 25 years, Nepal has one of the highest incidence of typhoid fever. Therefore we collected information from hospitals in the Kathmandu Valley from over the past five years. There were 9901 enteric fever cases between January 2008 and July 2012. 1,881 of these were confirmed typhoid cases from five hospitals in the Kathmandu district. Approximately 70% of the cases involved children under 15 years old. 1281 cases were confirmed as S. Paratyphi. Vaccines should be prioritized for control of typhoid in conjunction with improved water and sanitation conditions in Nepal and in endemic countries of Asia and Africa.     

Genomics of immune response to typhoid and cholera vaccines

Considerable variation in antibody response (AR) was observed among recipients of an injectable typhoid vaccine and an oral cholera vaccine. We sought to find whether polymorphisms in genes of the immune system, both innate and adaptive, were associated with the observed variation in response. For both vaccines, we were able to discover and validate several polymorphisms that were significantly associated with immune response. For the typhoid vaccines, these polymorphisms were on genes that belonged to pathways of polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and eventual production of antimicrobial peptides. For the cholera vaccine, the pathways included epithelial barrier integrity, intestinal homeostasis and leucocyte recruitment. Even though traditional wisdom indicates that both vaccines should act as T-cell-independent antigens, our findings reveal that the vaccines induce AR using different pathways.     

Unsaturated vitamin B12 binding capacity and serum lysozyme activity during the marrow granulocytes reserve tests.

Unsaturated vitamin B12 binding capacity (UBBC) and serum lysozyme activity (LZM) were estimated durinng the endotoxin, prednisone and hydrocortisone marrow granulocyte reserve (MGR) pool tests. Our results showed, that no additional mechanism except the shift of MGR from marrow caused granulocytosis after typhoid vaccine administration. While the prednisone, when given orally diminished additionally the number of the physiologically destroyed neutrophils. The hydrocortisone, however, showed the results very similar to those obtained after typhoid vaccine adminstration. Thus the hydrocortisone test seems to be most useful. It gives as good information as typhoid vaccine test but does not show its side-effects.     

Intradermal antityphoid-antitetanus vaccination by jet injection.

A lyophilized, heat-killed, phenol preserved typhoid vaccine (5 x 10(8) cells) suspended in 0.1 ml unadsorbed concentrated tetanus vaccine (10 Lf) was administered in man by intradermal route. This association of the two vaccines resulted in milder postvaccinal reactions: moreover, the immunological properties of typhoid vaccine, as certified by the passive protection test of the mouse with sera of the vaccines and the H and O agglutinin titres found in these immune sera, were perfectly conserved. Consequently, the mixed typhoid-tetanus vaccination in man by intradermal route is possible and advantageous for practical and economical reasons.     

Genetic determinants of immune-response to a polysaccharide vaccine for typhoid

Differences in immunological response among vaccine recipients are determined both by their genetic differences and environmental factors. Knowledge of genetic determinants of immunological response to a vaccine can be used to design a vaccine that circumvents immunogenetic restrictions. The currently available vaccine for typhoid is a pure polysaccharide vaccine, immune response to which is T-cell independent. Little is known about whether genetic variation among vaccinees associates with variation in their antibody response to a polysaccharide vaccine. We conducted a study on 1,000 individuals resident in an area at high-risk for typhoid; vaccinated them with the typhoid vaccine, measured their antibody response to the vaccine, assayed >2,000 curated SNPs chosen from 283 genes that are known to participate in immune-response; and analyzed these data using a strategy to (a) minimize the statistical problems associated with testing of multiple hypotheses, and (b) internally cross-validate inferences, using a half-sample design, with little loss of statistical power. The first stage analysis, using the first half-sample, identified 54 SNPs in 43 genes to be significantly associated with immune response. In the second-stage, these inferences were cross-validated using the second half-sample. First-stage results of only 8 SNPs (out of 54) in 7 genes (out of 43) were cross-validated. We tested additional SNPs in these 7 genes, and found 8 more SNPs to be significantly associated. Haplotypes constructed with these SNPs in these 7 genes also showed significant association. These 7 genes are DEFB1, TLR1, IL1RL1, CTLA4, MAPK8, CD86 and IL17D. The overall picture that has emerged from this study is that (a) immune response to polysaccharide antigens is qualitatively different from that to protein antigens, and (b) polymorphisms in genes involved in polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signaling and eventual production of antimicrobial peptides are associated with antibody response to the polysaccharide vaccine for typhoid. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11568-010-9134-1) contains supplementary material, which is available to authorized users.     

Specific antibodies bound to secretory IgA in the sera of patients with intestinal infections]

Specific IgA and sIgA antibodies were studied in the sera of patients suffering from various intestinal diseases (dysentery, salmonellosis, typhoid fever, chronic typhoid carrier state) and in the sera of healthy persons immunized by parenteral route with typhoid alcohol vaccine. The nature of antibodies was identified in Coombs' test, using monospecific antisera to alpha-chain and to the secretory component. IgA and sIgA antibodies were revealed most frequently in the sera of dysentery patients and of chronic typhoid carriers. No sIgA antibodies were found in the sera of subcutaneously immunized persons. The presence of specific sIgA antibodies in the serum reflects the participation of local immune mechanisms in the formation of systemic immunity in the intestinal infections.     

Development of specific cellular immunoreactivity in typhoid fever.

Development of cellular immunoreactivity to Salmonella typhi and Salmonella paratyphi-A was studied by the leukocyte migration inhibition test in 9 patients with typhoid fever and in 2 patients with paratyphoid fever. Cellular reactivity could be demonstrated from the first days of the disease in all the subjects. The most pronounced migration inhibition was observed during the febrile period. It is suggested that specific cellular reactivity may play a pathogenetic role in typhoid fever.     

The effect of immunostimulants on the resistance of white mice to the causative agent of typhoid fever

The influence of prodigiosan, salmosan, polyribonate and levamisole on the body nonspecific and specific resistance to S. typhi strain 4446 has been studied. Prodigiosan and salmosan have proved to be the most effective. The injection of these compounds simultaneously with typhoid vaccine (both chemical adsorbed vaccine and alcohol-treated vaccine, enriched with Vi-antigen) significantly increases the survival rate of immunized animals (by 35-45%), elevates the resistance index (1.5- to 2.3-fold) and the effectiveness index of the vaccine (17- to 32-fold) in comparison with the controls. Besides, prodigiosan and salmosan alone are capable of increasing nonspecific resistance to S. typhi strain 4446, which is manifested by an increase of the survival rate of stimulated animals by 61.87%. Proceeding from the results thus obtained, the possibility of good prospects for prodigiosan and salmosan in the prophylaxis of typhoid fever in humans may be inferred.     

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.     

Stability of cholera and typhoid vaccines

Fluid plain and adsorbed and freeze-dried cholera and tyhpoid vaccines of different composition were examined for thermostability by potency testing (by active mouse protection tests) after exposure to 37 degrees C for 1, 2, 3, 4, 8 and 12 weeks. Loss of potency was evaluated by comparison with samples stored at 4 degrees C. The fluid plain cholera vaccine remained fully potent for 1--3 weeks, the adsorbed vaccine for at least 4 weeks. The fluid typhoid vaccines showed greater thermosensitivity than the fluid plain cholera vaccine. The freeze-dried cholera and typhoid vaccines were both very stable, retaining fully potency after at least 12 weeks' exposure to 37 degrees C. It should be emphasized that the above results apply exclusively to vaccines prepared by the methods used by the authors and formulated to identical compositions.     

A mouse model for the human pathogen Salmonella typhi

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a life-threatening human disease. The lack of animal models due to S. Typhi's strict human host specificity has hindered its study and vaccine development. We find that immunodeficient Rag2(-/-) γc(-/-) mice engrafted with human fetal liver hematopoietic stem and progenitor cells are able to support?S. Typhi replication and persistent infection. A?S. Typhi mutant in a gene required for virulence in humans was unable to replicate in these mice. Another mutant unable to produce typhoid toxin exhibited increased replication, suggesting a role for this toxin in the establishment of persistent infection. Furthermore, infected animals mounted human innate and adaptive immune responses to S. Typhi, resulting in the production of cytokines and pathogen-specific antibodies. We expect that this mouse model will be a useful resource for understanding S.?Typhi pathogenesis and for evaluating potential vaccine candidates against typhoid fever.