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.     

Effect of a live enteral dysentery vaccine from spontaneous Flexner mutant 2a 516m on the immunoglobulin-producing cell count in the large intestine mucosa in dysentery

The influence of vaccinal therapy with live oral dysentery vaccine prepared from S. flexneri 2a 516M on the content of immunoglobulin-producing cells in the mucous membrane of the large intestine was studied. A considerable increase in the number of IgA- and IgM-synthetizing cells was shown to occur in the course of the infectious process in acute dysentery. In chronic dysentery the content of IgA- and IgM-synthetizing cells in patients was considerably lower than in a smooth course of acute dysentery. The use of the vaccine for the therapy of patients with chronic and especially acute dysentery resulted in a considerable rise in the number of plasma cells synthetizing IgA, IgM and IgG.     

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.     

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.     

Immunoglobulin and antibody content in the blood serum, coprofiltrate and saliva of patients with Sonne dysentery]

The authors studied the immunoglobulin and specific antibodies content of various classes in the serum, coprofiltrates and the saliva of 68 patients suffering from Sonne dysentery and in 48 healthy adult persons. Mancini's test demonstrated a significant elevation of IgG and IgM content in the blood of dysentery patients in comparison with that in healthy persons, and the absence of any changes in the IgA content. The titres of specific IgG-, IgA- and IgM-antibodies in determination in the modified Coombs' test increased consideerably during dysentery infection and were found in high titres during the first week of the disease; they reached the maximum during the second week and persisted at this level for 3 weeks. The greatest antibody elevation was in the IgA-class. Antibodies revealed in the coprofiltrates and the saliva of dysentery patients belonged to IgA- and IgG-class. There proved to be a correlation of the antibody changes in these two secretions.     

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.     

Results of the research on the preparation and testing of live oral smallpox vaccine in tablet form]

The authors sum up the results of decade of investigations on the elaboration and trial of live oral smallpox vaccine in tablet form. A conclusion was made that due to mild reactogenic properties, satisfactory immunogenicity and weak allergy producing properties, the mentioned preparation, along with a possibility of express and mass use, can posses future prospects under conditions of final smallpox eradication.     

Serological method of detecting the antigens of the causative agent of Sonne dysentery in lysates of the fecal inoculates from patients]

Serological method of detection of Sh. sonnei antigens in the lysates of the patients, fecal cultures is suggested and approved. In the majority of cases of the results of bacteriological and serological methods of study of the feces coincided. Data confirming the specificity of the antibody neutralization test (ANT) in Sonne dysentery are presented. In connection with detection of the screening action of the Vi-antigen of typhoid bacilli there were elaborated additional methods for verifying the specificity of the ANT results. It is recommended to keep agar plates after selection of suspicious colonies during the bacteriological test; the lysate of the microbial crop should be additionally subjected to the ANT, this considerably increasing the percentage of laboratory confirmations of dysentery caused by Sh. sonnei.     

Reactogenicity and immunological effectiveness of an oral cholera chemical vaccine in a limited controlled experiment with human revaccination]

Oral cholera chemical vaccine in the doses tested (2 and 3 tablets) proved to be areactogenic, harmless and immunologically effective in a controlled limited trial in 150 volunteers. By the results of titration of specific antitoxins and vibriocidal antibodies in the blood serum, as well as of coproantibodies a dose of 2 tablets was chosen as the optimal one.     

Safety and immunogenicity following administration of a live, attenuated monovalent 2009 H1N1 influenza vaccine to children and adults in two randomized controlled trials

Background

The safety, tolerability, and immunogenicity of a monovalent intranasal 2009 A/H1N1 live attenuated influenza vaccine (LAIV) were evaluated in children and adults.

Methods/Principal Findings

Two randomized, double-blind, placebo-controlled studies were completed in children (2–17 y) and adults (18–49 y). Subjects were assigned 4∶1 to receive 2 doses of H1N1 LAIV or placebo 28 days apart. The primary safety endpoint was fever ≥38.3°C during days 1–8 after the first dose; the primary immunogenicity endpoint was the proportion of subjects experiencing a postdose seroresponse. Solicited symptoms and adverse events were recorded for 14 days after each dose and safety data were collected for 180 days post-final dose. In total, 326 children (H1N1 LAIV, n = 261; placebo, n = 65) and 300 adults (H1N1 LAIV, n = 240; placebo, n = 60) were enrolled. After dose 1, fever ≥38.3°C occurred in 4 (1.5%) pediatric vaccine recipients and 1 (1.5%) placebo recipient (rate difference, 0%; 95% CI: –6.4%, 3.1%). No adults experienced fever following dose 1. Seroresponse rates in children (H1N1 LAIV vs. placebo) were 11.1% vs. 6.3% after dose 1 (rate difference, 4.8%; 95% CI: –9.6%, 13.8%) and 32.0% vs. 14.5% after dose 2 (rate difference, 17.5%; 95% CI: 5.5%, 27.1%). Seroresponse rates in adults were 6.1% vs. 0% (rate difference, 6.1%; 95% CI: –5.6%, 12.6%) and 14.9% vs. 5.6% (rate difference, 9.3%; 95% CI: –0.8%, 16.3%) after dose 1 and dose 2, respectively. Solicited symptoms after dose 1 (H1N1 LAIV vs. placebo) occurred in 37.5% vs. 32.3% of children and 41.7% vs. 31.7% of adults. Solicited symptoms occurred less frequently after dose 2 in adults and children. No vaccine-related serious adverse events occurred.

Conclusions/Significance

In subjects aged 2 to 49 years, two doses of H1N1 LAIV have a safety and immunogenicity profile similar to other previously studied and efficacious formulations of seasonal trivalent LAIV.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00946101","term_id":"NCT00946101"}}NCT00946101, {"type":"clinical-trial","attrs":{"text":"NCT00945893","term_id":"NCT00945893"}}NCT00945893     

Construction and characterization of a live attenuated Shigella flexneri 2a vaccine strain, sf301 Delta virG and dsbA33G]

Construction and characterization of a live attenuated Shigella flexneria 2a sf301 vaccine strain to prevent the endemic of shigellosis. Using Chinese majority epidemic Shigella flexneri 2a serotype sf301 as the target, p Delta virG, a deletion derivation of the virG gene in the SacB suicide vector pCVD442 and pDsbA33G, an mutant of a disulfide bond catalyst DsbA, replaced its 33 amiano acid Cystine by Glycerin in pCVD442, were used to generate a attenuated mutant strain sf301: Delta virG: DsbA33 G. Its virulence was evaluated by Sereny test, the invasive ability was detected by HeLa cell invasive assay, immunogenicity was detected by immunized Guinea pigs through inoculated guinea pigs' conjunctive sac. Sereny test was negative and HeLa invasive assay showed sf301: Delta virG: DsbA33 G retained partial invasive ability. In contrast to control group, sf301: Delta virG: DsbA33 G could induced significantly high antibody levels of IgA and IgG against sf301 LPS in animal's mucosal lavage fluids and sera in both primary immunization protocol and boosting protocol. The numbers of ASCs in local draining lymph nodes and spleens were significantly higher than control group. The immune response to sf301: Delta virG: DsbA33 G could provide completely protection from the challenge of wild type sf301. sf301: Delta virG: DsbA33 G is a safe and effective oral candidate vaccine to prevent the infection of Shigella strains.     

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.     

风疹减毒活疫苗主种子批毒种(松叶株)的安全性和免疫原性检测

评价兰州生物制品研究所用风疹病毒松叶株主种子批毒种制备的冻干风疹减毒活疫苗的安全性和免疫原性。采用自身对照、开放性的免疫原性临床观察试验,对100名8～10月龄筛选后符合条件的健康易感儿童,皮下接种1剂风疹减毒活疫苗,观察其免疫后的局部和全身反应并采集每个受试者免前和免后35d的血清标本,检测风疹HI抗体,计算阳转率和几何平均滴度。试验中所有受试者在系统观察期内均未观察到注射部位局部的不良反应;总的发热率为5%,且均为轻度发热;有1例在观察期内出现腹泻和咳嗽并持续5d,发生率为1%,属中度全身反应;血清风疹病毒抗体(HI)阳转率为100%,GMT为1:638.7±1.7。该疫苗与国内、外其它种类的风疹疫苗一样具有良好的安全性和免疫原性。     

Safety, efficacy and effectiveness of cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine in adults and children.

Studies in children and adults revealed cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine (CAIV-T) to be well accepted, well tolerated and highly protective against culture-confirmed influenza, and to provide significant health benefits. A 2 year, multicentre, double-blind, placebo-controlled efficacy field trial of CAIV-T in children aged 15-71 months with annual re-immunization revealed the vaccine to be highly protective against culture-confirmed influenza. Vaccine induced serum and secretory antibodies in vaccinated children. Overall, during 2 years of study, vaccine was 92% protective against culture-confirmed influenza. During the second year of study the vaccine was 86% protective against influenza A/Sydney/5/97-like virus, a significantly drifted strain not well matched to the vaccine. Antibody studies on children given CAIV-T revealed that high titres of cross-reacting antibodies to influenza A/Sydney/5/97 were induced with vaccination by live attenuated influenza A/Wuhan/359/95-like vaccine. Effectiveness measures revealed significant reductions in febrile illness (21% reduction in year 1, 19% reduction in year 2), febrile otitis media (33% reduction in year 1, 16% reduction in year 2) and associated antibiotic use among vaccinated children compared with placebo recipients. In adults, vaccination with CAIV-T resulted in protection during experimental challenge with virulent wild-type viruses. An effectiveness trial in adults demonstrated significant benefits of CAIV-T vaccine (28% reduction in days of missed work for febrile upper respiratory illness days with associated 45% reduction in days taking antibiotics). General use of CAIV-T has the potential to significantly reduce the impact of influenza in children and adults.     

Immunogenicity and safety assessment of the Cuban recombinant hepatitis B vaccine in healthy adults.

Manufactures of biotechnological/biological products (including vaccines) frequently make changes to manufacturing processes of products both during development and after approval. In our case, a non-inferiority bridging study was carried out to demonstrate that changes in the production plant facilities of Cuban recombinant hepatitis B vaccine, Heberbiovac HB, did not affect the safety and immunogenicity of the vaccine. This controlled, randomized, doubled-blinded trial included 501 volunteers, aged between 20 and 64, who were given three doses of vaccine (20 microg HBsAg/mL) at month 0, 1, and 2. Four lots were evaluated (three corresponding to the new production facilities and a control one produced in the older facilities). One month after the third dose, were observed protective levels of anti-HBsAg in 97% of the subjects that concluded the study with a geometric mean antibody titer (GMT) of 931.18 IU/L. Normal values of body mass index (BMI), the younger ages, and being a female, were significantly related to a good antibody response. The vaccine was well tolerated. Pain at the injection site was the most commonly reported symptom. We conclude that Heberbiovac HB vaccine maintains its characteristics after the modifications carried out in the production plant facilities and both, lot obtained in previous facilities and in the new ones, are comparable in terms of safety and immunogenicity.     

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.     

Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine

Oral vaccines, whether living or non-living, viral or bacterial, elicit diminished immune responses or have lower efficacy in developing countries than in developed countries. Here I describe studies with a live oral cholera vaccine that include older children no longer deriving immune support from breast milk or maternal antibodies and that identify some of the factors accounting for the lower immunogenicity, as well as suggesting counter-measures that may enhance the effectiveness of oral immunization in developing countries. The fundamental breakthrough is likely to require reversing effects of the 'environmental enteropathy' that is often present in children living in fecally contaminated, impoverished environments.