Ribosomal Vaccine Research Articles

Immunoprophylaxis of infections of the upper respiratory tract in the frequently ill children

The review of the clinical studies designed to evaluate the prophylactic effectiveness of ribosomal immunization is presented. It is shown that the application of the ribosomal vaccine ribomunyl causes a significant reduction in the occurrence of acute respiratory infections in the frequently ill children, lowers the frequency of exacerbation of chronic diseases of the upper respiratory tract, and allows to decrease the use of antibiotics. The authors emphasize the high therapeutic effectiveness and safety of preventive measures against respiratory infections in the frequently ill children with the use of the anti-influenza vaccine in combination with ribosomal immunization.

Differences in Chemical Composition and Antigenicity between Two Ribosomal Vaccines Prepared from Pasteurella piscicida

Differences in Chemical Composition and Antigenicity between Two Ribosomal Vaccines Prepared from Pasteurella piscicida

BALB/c Mice Vaccinated withLeishmania majorRibosomal Proteins Extracts Combined with CpG Oligodeoxynucleotides Become Resistant to Disease Caused by a Secondary Parasite Challenge

Leishmaniasis is an increasing public health problem and effective vaccines are not currently available. We have previously demonstrated that vaccination with ribosomal proteins extracts administered in combination of CpG oligodeoxynucleotides protects susceptible BALB/c mice against primary Leishmania major infection. Here, we evaluate the long-term immunity to secondary infection conferred by this vaccine. We show that vaccinated and infected BALB/c mice were able to control a secondary Leishmania major challenge, since no inflammation and very low number of parasites were observed in the site of reinfection. In addition, although an increment in the parasite burden was observed in the draining lymph nodes of the primary site of infection we did not detected inflammatory lesions at that site. Resistance against reinfection correlated to a predominant Th1 response against parasite antigens. Thus, cell cultures established from spleens and the draining lymph node of the secondary site of infection produced high levels of parasite specific IFN-γ in the absence of IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high IgG2a/IgG1 ratio for anti-Leishmania antibodies. Our results suggest that ribosomal vaccine, which prevents pathology in a primary challenge, in combination with parasite persistence might be effective for long-term maintenance of immunity.

Cost effective analysis of ribosome-component immune modulation

In childhood, recurrent airway infections are the most common cause for medical visits and hospitalizations. Their economic impact is considerable and their treatment accounts for a substantial quota of the health care budget. Despite documented efficacy and safety, ribosomal bacterial vaccine and membrane fraction use is still limited by being prevalently considered for prevention rather than treatment. The objective of this study was to analyze the economic benefit achieved with ribosomal immunotherapy. A review was performed of available literature data on economic parameters. Pharmacoeconomic studies published during the past few years showed how the use of ribosome component immune modulator is capable of reducing expenditure associated with treatment of recurrent respiratory infection and allows achievement of substantial savings in terms of cost, time, and loss of productivity. The initial cost of prevention in patients suffering from chronic respiratory infections is offset by a subsequent saving arising from less recurrence of disease. Direct management costs such as therapy courses, medical visits, medical exams, hospitalizations, etc., and indirect costs such as absence from school and work are not routinely considered by primary care physicians.

Ribosomal immunotherapy for recurrent respiratory tract infections in children.

Recurrent respiratory tract infections are common in children. They reflect the immaturity of the immune system in its encounter with environmental antigens. Little or no specific protective immune response has yet been established. These infections represent an important public health problem in terms of both treatment (anti-inflammatory or antibacterial drugs for children) and economy. Immunotherapy has been proposed as a means of preventing these recurrent infections by providing children with small doses of inactive bacterial antigens liable to trigger specific and protective immune responses. Among such drugs, ribosomal preparations (to which this review is limited) appear to be not only well tolerated, but also ideally targeted to induce mucosal responses. One preparation of ribosomal mucosal vaccine is commercially available in several countries. Numerous clinical trials in the world have confirmed the positive role of this mucosal ribosomal bacterial vaccine in significantly reducing the number of infections, courses of antibacterials, and absenteeism. In vitro and ex vivo investigations have confirmed that such vaccines indeed trigger protective specific immune responses.

Meta-Analysis of Published Clinical Trials of a Ribosomal Vaccine (Ribomunyl?? *) in Prevention of Respiratory Infections

To perform a meta-analysis using data from all clinical trials and studies of a ribosomal vaccine (Ribomunyl((R))) in order to estimate its overall effect on the number of infections and antibacterial courses used per person. Meta-analysis of studies performed between 1985 and 1999 in 7 European countries and also in Kazakhstan, Tunisia, Morocco and Argentina. Information from 14 213 adults and children. There were 9 randomised, double-blind, placebo-controlled studies, 3 randomised nonblind studies and 16 nonblind studies with no placebo arm in which the response to ribosomal vaccine was compared with historical information. The mean number of infections per person in a study period of 3 months using placebo was found to be 2.39 (standard error +/- 0.50), and in a study period of 6 months was 3.35 (+/-0.41) infections. In both study periods, ribosomal vaccine use was associated with a reduction in the number of infections per person of 1.43 (+/-0.26). In the study period, patients on placebo reported 3.02 (+/-0.44) antibacterial courses, whereas ribosomal vaccine was associated with a reduction of 1.32 (+/-0.42) antibacterial courses. In spite of variability in data quality, and the small sample size in some of the studies, we conclude that in patients with recurrent respiratory infections ribosomal vaccine significantly reduces both the number of infections and the number of antibacterial courses compared with placebo. This study is a strong and objective demonstration of the efficacy of ribosomal vaccine in limiting the number of otorhinolaryngological infections in children and adults.

Ribosomal vaccine favoured in respiratory tract infection

Ribosomal vaccine favoured in respiratory tract infection

Ribosomal vaccine favoured in respiratory tract infection

Ribosomal vaccine favoured in respiratory tract infection

Cost of ribosomal vaccine offset by avoided rhinitis episodes

Cost of ribosomal vaccine offset by avoided rhinitis episodes

Pseudomonas aeruginosa antigens as potential vaccines

Pseudomonas aeruginosa is one of the most important opportunistic bacterial pathogens in humans and animals. This organism is ubiquitous and has high intrinsic resistance to antibiotics due to the low permeability of the outer membrane and the presence of numerous multiple drug efflux pumps. Various cell-associated and secreted antigens of P. aeruginosa have been the subject of vaccine development. Among pseudomonas antigens, the mucoid substance, which is an extracellular slime consisting predominantly of alginate, was found to be heterogeneous in terms of size and immunogenicity. High molecular mass alginate components (30–300 kDa) appear to contain conserved epitopes while lower molecular mass alginate components (10–30 kDa) possess conserved epitopes in addition to unique epitopes. Surface-exposed antigens including O-antigens (O-specific polysaccharide of LPS) or H-antigens (flagellar antigens) have been used for serotyping due to their highly immunogenic nature. Chemical structures of repeating units of O-specific polysaccharides have been elucidated and these data allowed the identification of 31 chemotypes of P. aeruginosa. Conserved epitopes among all serotypes of P. aeruginosa are located in the core oligosaccharide and the lipid A region of LPS and immunogens containing these epitopes induce cross-protective immunity in mice against different P. aeruginosa immunotypes. To examine the protective properties of OM proteins, a vaccine containing P. aeruginosa OM proteins of molecular masses ranging from 20 to 100 kDa has been used in pre-clinical and clinical trials. This vaccine was efficacious in animal models against P. aeruginosa challenge and induced high levels of specific antibodies in human volunteers. Plasma from human volunteers containing anti- P. aeruginosa antibodies provided passive protection and helped the recovery of 87% of patients with severe forms of P. aeruginosa infection. Vaccines prepared from P. aeruginosa ribosomes induced protective immunity in mice, but the efficacy of ribosomal vaccines in humans is not yet known. A number of recent studies indicated the potential of some P. aeruginosa antigens that deserve attention as new vaccine candidates. The outer core of LPS was implicated to be a ligand for binding of P. aeruginosa to airway and ocular epithelial cells of animals. However, heterogeneity exists in this outer core region among different serotypes. Epitopes in the inner core are highly conserved and it has been demonstrated to be surface-accessible, and not masked by O-specific polysaccharide. The use of an in vivo selection/expression technology (IVET) by a group of researchers identified a number of P. aeruginosa proteins that are expressed in vivo and essential for virulence. Two of these in vivo-expressed proteins are FptA (ferripyochelin receptor protein) and a homologue of an LPS biosynthetic enzyme. Our laboratory has identified a highly conserved protein, WbpM, and P. aeruginosa with a deficiency in this protein produces only rough LPS and became serum sensitive. Results from these studies have provided the foundation for a variety of vaccine formulations.

Pseudomonas aeruginosa antigens as potential vaccines.

Pseudomonas aeruginosa is one of the most important opportunistic bacterial pathogens in humans and animals. This organism is ubiquitous and has high intrinsic resistance to antibiotics due to the low permeability of the outer membrane and the presence of numerous multiple drug efflux pumps. Various cell-associated and secreted antigens of P. aeruginosa have been the subject of vaccine development. Among pseudomonas antigens, the mucoid substance, which is an extracellular slime consisting predominantly of alginate, was found to be heterogenous in terms of size and immunogenicity. High molecular mass alginate components (30-300 kDa) appear to contain conserved epitopes while lower molecular mass alginate components (10-30 kDa) possess conserved epitopes in addition to unique epitopes. Surface-exposed antigens including O-antigens (O-specific polysaccharide of LPS) or H-antigens (flagellar antigens) have been used for serotyping due to their highly immunogenic nature. Chemical structures of repeating units of O-specific polysaccharides have been elucidated and these data allowed the identification of 31 chemotypes of P. aeruginosa. Conserved epitopes among all serotypes of P. aeruginosa are located in the core oligosaccharide and the lipid A region of LPS and immunogens containing these epitopes induce cross-protective immunity in mice against different P. aeruginosa immunotypes. To examine the protective properties of OM proteins, a vaccine containing P. aeruginosa OM proteins of molecular masses ranging from 20 to 100 kDa has been used in pre-clinical and clinical trials. This vaccine was efficacious in animal models against P. aeruginosa challenge and induced high levels of specific antibodies in human volunteers. Plasma from human volunteers containing anti-P. aeruginosa antibodies provided passive protection and helped the recovery of 87% of patients with severe forms of P. aeruginosa infection. Vaccines prepared from P. aeruginosa ribosomes induced protective immunity in mice, but the efficacy of ribosomal vaccines in humans is not yet known. A number of recent studies indicated the potential of some P. aeruginosa antigens that deserve attention as new vaccine candidates. The outer core of LPS was implicated to be a ligand for binding of P. aeruginosa to airway and ocular epithelial cells of animals. However, heterogeneity exists in this outer core region among different serotypes. Epitopes in the inner core are highly conserved and it has been demonstrated to be surface-accessible, and not masked by O-specific polysaccharide. The use of an in vivo selection/expression technology (IVET) by a group of researchers identified a number of P. aeruginosa proteins that are expressed in vivo and essential for virulence. Two of these in vivo-expressed proteins are FptA (ferripyochelin receptor protein) and a homologue of an LPS biosynthetic enzyme. Our laboratory has identified a highly conserved protein, WbpM, and P. aeruginosa with a deficiency in this protein produces only rough LPS and became serum sensitive. Results from these studies have provided the foundation for a variety of vaccine formulations.

Identification and nucleotide sequence of Brucella melitensis L7/L12 ribosomal protein

DNA sequencing of the gene encoding a Brucella melitensis 12-kDa protein revealed that this protein was the ribosomal protein L7/L12. The B. melitensis L7/L12 DNA sequence was identical to that of the corresponding B. abortus gene, showing the near identity of these two organisms. When comparing the sequence of this protein to that of other organisms some domains were highly conserved, especially the C-terminus, which contrasted with the lack of conservation of the sequences at the N-terminus. The finding that the ribosomal protein L7/L12 of Brucella is an immunodominant antigen provides a new rationale to explain the activity of ribosomal vaccines.

Identification and nucleotide sequence of Brucella melitensis L7/L12 ribosomal protein.

DNA sequencing of the gene encoding a Brucella melitensis 12-kDa protein revealed that this protein was the ribosomal protein L7/L12. The B. melitensis L7/L12 DNA sequence was identical to that of the corresponding B. abortus gene, showing the near identity of these two organisms. When comparing the sequence of this protein to that of other organisms some domains were highly conserved, especially the C-terminus, which contrasted with the lack of conservation of the sequences at the N-terminus. The finding that the ribosomal protein L7/L12 of Brucella is an immunodominant antigen provides a new rationale to explain the activity of ribosomal vaccines.

Protective ribosomal preparation from Shigella sonnei as a parenteral candidate vaccine

A parenteral Shigella ribosomal vaccine (SRV) was investigated in animals for safety, antibody-inducing capacity, and protective activity. Ribosomal preparations from a Shigella sonnei phase I avirulent strain were obtained and shown to possess chemical, sedimentation, and other properties typical of bacterial ribosomes. No endotoxin contamination was revealed by a ketodeoxyoctonate assay, although the presence of some kind of O antigen was evidenced by serological findings and the high activity of SRV in inducing the O-antibody response and immunological memory in animals. SRV was nontoxic in mice, guinea pigs, and monkeys and induced no local reactions when injected subcutaneously in reasonable doses. Significant protection against a local Shigella infection (Sereny test) was seen in guinea pigs injected with SRV (efficiency index, about 60%) and the specificity of the protection was evident from cross-challenge experiments. The protective efficiency of SRV was especially high in rhesus monkeys challenged orally with virulent Shigella cells (89%, as calculated from the summarized data of several experiments in 71 animals). Protection in monkeys was long lasting and could be demonstrated several months after injection of SRV. An inexpensive technique can be used for the production of SRV on a large scale. The high immunogenicity of SRV is discussed in terms of the amplifying effect of the ribosome, which serves as a delivery system for polysaccharide O antigen. Further study of SRV as a candidate vaccine for humans seems justified by the data obtained.

Requirement of the conformational stability of aSalmonellaribosomal vaccine for its mouse protection

The 43-kDa non-O antigenic component isolated from the crude ribosomal fraction of Salmonella typhimurium [9] was further purified by affinity chromatography (43-kDa protein: 43-kDp). Immunization with 43-kDp did not induce complete mouse protection in CF1 mice to 500 LD50 of S. typhimurium, although it elicited a substantial IgG antibody response. The 43-kDp exhibited the mitogenicity to splenocytes (CF1 and C3H/HeJ) and B cell-rich populations (CF1). Complexing 43-kDp with the compact ribosomes of Streptococcus pyogenes by formaldehyde (complex vaccine: CV) elicited both IgM and IgG antibodies to 43-kDp. CV induced a boosting effect to enhance IgG antibody response. Moreover, CV generated delayed-type hypersensitivity to salmonella antigens and also conferred complete protection against 500 LD50 challenge of S. typhimurium to CF1 mice. These abilities of CV were reduced or impaired by RNase digestion. CV was able to induce partial or complete protection in inbred mouse strains (C3H/HeN, C3H/HeJ, DBA/2 and A/J). These data, in addition to other reports, suggest that conformational stability between ribosomes and contaminating substances such as 43-kDp or O-antigens might be required for the overall effects of the ribosomal vaccine.

Requirement of the conformational stability of a Salmonella ribosomal vaccine for its mouse protection

Requirement of the conformational stability of a Salmonella ribosomal vaccine for its mouse protection

Polysaccharide nature of O antigen in protective ribosomal preparations from Shigella: Experimental evidence and implications for the ribosomal vaccine concept

Shigella ribosomal vaccine (SRV) was previously shown to be highly active in induction of mucosal and systemic O-antibody response and protection against Shigella infection in guinea pigs and monkeys. In this study, the O-specific component (OSC) was isolated from the SRV by affinity chromatography using rabbit O antibodies coupled to CNBr-Sepharose. The results of the reaction with carbocyanine dye as well as chemical data show that ribosomal OSC is devoid of lipid A and KDO, which are characteristic of classical LPS. The comparison of OSC with various LPS-related substances led to the conclusion that ribosomal OSC is similar to and probably identical with cytoplasmic O polysaccharide (L hapten), an O-side-chain polymer which accumulates in cytoplasm.It is hypothesized that the extremely high immunogenicity of SRV depends on a cooperative action of OSC, representing an epitope-specific part of the vaccine, and a ribosomal particle which serves as a vector, providing amplification of the immunogenic effect. The data obtained indicate the presence of a non-covalent link between the two components of the ribosomal vaccine.

Increase in specific antibody-forming cells in human tonsils after oral stimulation with D-53 a ribosomal vaccine

Thirty subjects who had received an oral ribosomal vaccine to common bacteria of upper respiratory tract infections, and ten controls were tonsillectomized for recurrent infections or rhonchologic pathology. A three-step indirect immunofluorescence technique was used to identify and enumerate specific antibody forming cells (SAFC) in their tonsils. Plasma-cells specific of the four strains being constituents of the oral vaccine ( H. influenzae, K. pneumonieae, S. pyogenes and S. pneumoniae) were observed in all samples. The numbers of SAFC were significantly higher in the subjects who had received the oral vaccine. These results support the efficiency or oral immunization in increasing local defenses, even at distance from the sensitized gut-associated lymphoid tissue. These data provide evidence for the homing phenomenon in human mucosae associated lymphoid tissue (MALT).

Protective Milk O Antibodies Induced in Guinea Pigs by Parenteral <i>Shigella </i>Ribosomal Vaccine

IgG and IgA O antibodies were studied in milk and sera of guinea pigs subcutaneously immunized at various stages of pregnancy with Shigella ribosomal vaccines (SRV) from Shigella sonnei and Shigella flexneri. Both vaccines induced O antibodies in milk, the level of IgA antibodies being significantly higher than that of IgG antibodies. The immune milk provided a clear-cut protection against experimental Shigella-induced keratoconjunctivitis. These results are consistent with the previously shown ability of parenteral SRV to stimulate gut-associated lymphoid tissue and confirm the involvement of secretory IgA O antibodies in the protection induced by the parenteral SRV. The high level of milk antibodies in vaccinated guinea pigs suggests the possibility to use the parenteral SRV for developing lactogenic immunity.

Protective capacity of a ribosomal vaccine against Candida albicans

Protective capacity of a ribosomal vaccine against Candida albicans