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S J Devi

Publications and source records attributed to S J Devi.

15 recordsLinked to original sources
PubMed1997

Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. The Multilaboratory Study Group.

A standardized serum bactericidal assay (SBA) is required to evaluate the functional activity of antibody produced in response to Neisseria meningitidis serogroup A and C vaccines. We evaluated assay parameters (assay buffer, target strains, growth of target cells, target cell number, complement source and concentration, and methods for growth of surviving bacteria) which may affect the reproducibility of SBA titers. The various assay parameters and specificity of anticapsular antibody to five serogroup A strains (A1, ATCC 13077, F8238, F9205, and F7485) and four serogroup C strains (C11, G7880, G8050, and 1002-90) were evaluated with Centers for Disease Control and Prevention meningococcal quality control sera. The critical assay parameters for the reproducible measurement of SBA titers were found to include the target strain, assay incubation time, and complement. The resulting standardized SBA was used by 10 laboratories to measure functional anticapsular antibody against serogroup A strains F8238 and serogroup C strain C11. In the multilaboratory study, SBA titers were measured in duplicate for 14 pairs of sera (seven adults and seven children) before and after immunization with a quadrivalent polysaccharide (A, C, Y, and W-135) vaccine. The standardized SBA was reliable in all laboratories regardless of experience in performing SBAs. For most sera, intralaboratory reproducibility was +/- 1 dilution; interlaboratory reproducibility was +/- 2 dilutions. The correlation between median titers (interlaboratory) and enzyme-linked immunosorbent assay total antibody concentrations was high for both serogroup A (r = 0.86; P < 0.001; slope = 0.5) and serogroup C (n = 0.86; P < 0.001; slope = 0.7). The specified assay, which includes the critical parameters of target strain, incubation time, and complement source, will facilitate interlaboratory comparisons of the functional antibody produced in response to current or developing serogroup A and C meningococcal vaccines.

Adult↗
PubMed1997

Preclinical evaluation of group B Neisseria meningitidis and Escherichia coli K92 capsular polysaccharide-protein conjugate vaccines in juvenile rhesus monkeys.

We reported the first use of group B meningococcal conjugate vaccines in a nonhuman primate model (S. J. N. Devi, C. E. Frasch, W. Zollinger, and P. J. Snoy, p. 427-429, in J. S. Evans, S. E. Yost, M. C. J. Maiden, and I. M. Feavers, ed., Proceedings of the Ninth International Pathogenic Neisseria Conference, 1994). Three different group B Neisseria meningitidis capsular polysaccharide (B PS)-protein conjugate vaccines and an Escherichia coli K92 capsular polysaccharide-tetanus toxoid (K92-TT) conjugate vaccine are here evaluated for safety and relative immunogenicities in juvenile rhesus monkeys with or without adjuvants. Monkeys were immunized intramuscularly with either B PS-cross-reactive material 197 conjugate, B PS-outer membrane vesicle (B-OMV) conjugate, or N-propionylated B PS-outer membrane protein 3 (N-pr. B-OMP3) conjugate vaccine with or without adjuvants at weeks 0, 6, and 14. A control group of monkeys received one injection of the purified B PS alone, and another group received three injections of B PS noncovalently complexed with OMV. Antibody responses as measured by enzyme-linked immunosorbent assay varied among individual monkeys. All vaccines except B PS and the K92-TT conjugate elicited a twofold or greater increase in total B PS antibodies after one immunization. All vaccines, including the K92-TT conjugate, elicited a rise in geometric mean B PS antibody levels of ninefold or more over the preimmune levels following the third immunization. Antibodies elicited by N-pr. B-OMP3 and B-OMV conjugates were directed to the N-propionylated or to the spacer-containing B PS antigens as well as to the native B PS complexed with methylated human serum albumin. None of the vaccines caused discernible safety-related symptoms.

Animals↗
PubMed1997

Bactericidal antibody responses of juvenile rhesus monkeys immunized with group B Neisseria meningitidis capsular polysaccharide-protein conjugate vaccines.

Reports on the bactericidal activities of antibodies to group B Neisseria meningitidis capsular polysaccharide (B PS) are conflicting. Using three different complement sources, we analyzed the bactericidal activities of sera of juvenile rhesus monkeys immunized with five conjugate vaccines of B PS synthesized by different schemes, an Escherichia coli K92 conjugate, and a noncovalent complex of B PS with group B meningococcal outer membrane vesicles (B+OMV) (S. J. N. Devi, W. D. Zollinger, P. J. Snoy, J. Y. Tai, P. Costantini, F. Norelli, R. Rappuoli, and C. E. Frasch, Infect. Immun. 65:1045-1052, 1997). With rabbit complement, nearly all preimmune sera showed relatively high bactericidal titers, and all vaccines, except the K92 conjugate, induced a fourfold or greater increase in bactericidal titers in most of the monkeys vaccinated. In contrast, with human complement, most prevaccination sera showed no bactericidal activity and in most of the vaccine groups, little or no increase in bactericidal titer was observed. However, the covalent conjugation of P BS and OMV (B-OMV) administered with and without the Ribi adjuvant induced relatively high bactericidal titers which persisted up to 30 weeks. An analysis of the specificities of bactericidal antibodies revealed that absorption with E. coli K1 cells did not change the bactericidal titer with human complement but reduced the titers observed with the rabbit and monkey complements. A significant increase in anti-lipopolysaccharide (LPS) antibodies was elicited by the B-OMV conjugates, and nearly all of the bactericidal activity with human complement could be inhibited with the purified group B meningococcal L3,7,8 LPS. B-OMV covalently coupled via adipic acid dihydrazide elicited significantly elevated levels (P < or = 0.02) of anti-OMV antibodies compared to those of the noncovalently complexed B+OMV. An initial small-scale evaluation of B PS conjugates in adult human males appears feasible, with careful monitoring, to settle the inconsistent reports of the importance of source of complement in eliciting bacteriolysis. Subsequent analysis of resultant human antibodies for bacteriolysis, opsonophagocytosis, and protective efficacy in animal models may be the first step toward answering safety- and efficacy-related concerns about B PS conjugate vaccines.

Animals↗
PubMed1996

Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model.

The encapsulated yeast, Cryptococcus neoformans, causes life-threatening meningoencephalitis in immunocompromised humans, especially in AIDS patients. Fatality and relapse rates remain quite high despite aggressive therapy. A conjugate vaccine composed of the cryptococcal capsular glucuronoxylomannan covalently coupled to tetanus toxoid (GXM-TT) was constructed and evaluated. The vaccine elicited high levels of capsular antibodies in mice by active and passive immunizations and conferred 70-80% protection against a moderate challenge with 10(3) C, neoformans. Monitoring of serum GXM and anti-GXM antibody levels and of incidence of cryptococcal isolation from various organs of mice suggested that presence of vaccine-induced antibodies during the first 4-6 weeks of infection is critical for clearance of cryptococci from various organs, for limiting serum GXM titers from reaching immunosuppressive levels and ultimately for survival. GXM-TT is the first defined fungal vaccine to confer antibody-mediated protection against a systemic mycosis in an animal model. GXM-TT is being evaluated for safety and immunogenicity in healthy and HIV-infected human volunteers at the National Institutes of Health.

Animals↗
PubMed1996

Binding diversity of monoclonal antibodies to alpha(2-->8) polysialic acid conjugated to outer membrane vesicle via adipic acid dihydrazide.

Murine monoclonal antibodies (mAbs) were generated using group B Neisseria meningitidis and Escherichia coli K1 polysaccharides (PSs) conjugated to outer membrane vesicle (OMV) via adipic acid dihydrazide, and were used to identify the immunodeterminants expressed on these capsular PSs. Ten mAbs representative of IgM and all subclasses of IgG were obtained which recognized diverse immunodeterminants on alpha(2-->8) polysialic acid (PSA). The specificity of mAbs to different antigenic determinants was assessed by their differential binding to PSA attached to a solid phase by different methods and confirmed by absorption studies. Two mAbs from the E. coli K1 fusion were directed to the O-acetyl epitope and the rest reacted with both the PSs only when attached to a solid phase by certain means. The methods by which PSA was coated on the solid phase had an impact on the epitope expression and binding pattern. At the concentrations used, the O-acetyl-specific mAbs, IgG1 and IgG3 mAbs were not bactericidal against group B N. meningitidis, whereas other mAbs were. The conjugates B and K1 PSs present to the murine immune system different antigenic determinants, some of which elicit bactericidal antibodies.

Adipates↗
PubMed1996

Preclinical immunoprophylactic and immunotherapeutic efficacy of antisera to capsular polysaccharide-tetanus toxoid conjugate vaccines of Vibrio vulnificus.

Vibrio vulnificus is an oyster-associated bacterial pathogen that causes life-threatening fulminating septicemia and necrotizing wound infections in humans. The capsular polysaccharide of V. vulnificus (VvPS) is critical for virulence. Previously we showed that active immunization of mice with a VvPS-tetanus toxoid (VvPS-TTa) conjugate vaccine conferred significantly higher protection against subsequent lethal challenge than immunization with VvPS alone. In the current study, we examined the utility of immunoprophylaxis or immunotherapy with hyperimmune antisera elicited by VvPS-TTa and VvPS-TTb conjugate vaccines prepared by different synthetic schemes. First we demonstrated that the Ribi adjuvant significantly enhanced the murine antibody response (P < or = 0.02) to both conjugates. Subsequently, high-titered polyclonal antisera were raised to VvPS-TTa and VvPS-TTb conjugate vaccines by using Ribi adjuvant or Freund's adjuvants. Antisera were observed to have protective effects when administered before and after acute lethal infection. All animals receiving prophylactic antisera intraperitoneally 24 h before lethal challenge with homologous carbotype 1 were protected, while 73 to 100% of control mice succumbed. Immunotherapy was also effective, with survival rates of 60 to 73% seen among mice when antisera were administered 2 h after bacterial challenge, at a time when symptoms of infection were already apparent. The protective effect of capsular antiserum appeared to be serotype specific. Antisera to the, carbotype 1 VvPS-TTa vaccine did not confer cross-protection against lethal challenge with carbotype 2 V. vulnificus despite partial structural similarity and a weak serological cross-reaction between the two carbotypes. Immune globulins induced by a potential multivalent VvPS conjugate vaccine composed of clinically prevalent carbotypes may have utility in the management of V. vulnificus infections and deserve further evaluation.

Animals↗
PubMed1995

Capsular polysaccharide-protein conjugate vaccines of carbotype 1 Vibrio vulnificus: construction, immunogenicity, and protective efficacy in a murine model.

Vibrio vulnificus causes septicemia and wound infections in immunocompromised humans. The capsular polysaccharide of Vibrio vulnificus (VvPS) is critical for virulence. We synthesized conjugate vaccines of carbotype 1 VvPS under conditions and in formulations suitable for human use. Purified VvPS was conjugated to tetanus toxoid (TT) or to inactivated V. vulnificus cytolysin or elastase by two different schemes. All conjugates elicited elevated anticapsular immunoglobulin G (IgG) and IgM and antiprotein IgG responses in mice compared with saline placebo. The conjugates prepared through caboxyl activation of VvPS (VvPS-TTa, VvPS-cytolysin, and VvPS-elastase) were more immunogenic than the one prepared through hydroxyl activation (VvPS-TTb). The protective efficacy of conjugated and unconjugated formulations of VvPS and that of protein carriers were evaluated in a mouse septicemia model. Eighty percent of mice actively immunized with VvPS-TTa vaccine survived challenge with carbotype 1 V. vulnificus, while VvPS-cytolysin and VvPS-elastase conjugates conferred 44 and 40% protection, respectively. Control mice immunized with VvPS, cytolysin, or elastase alone, or saline only, showed 70 to 100% mortality. VvPS-TTa vaccine is nontoxic, immunogenic, and protective in mice.

Animals↗
PubMed1995

Detection and quantitation of the glucuronoxylomannan-like polysaccharide antigen from clinical and nonclinical isolates of Trichosporon beigelii and implications for pathogenicity.

Sera from patients with systemic infections caused by the opportunistic fungus Trichosporon beigelii have been shown to cross-react with anticryptococcal antibodies. We quantitatively compared the amounts of antigen produced and examined the expression of O-acetyl epitopes from 35 strains of T. beigelii isolated from deep and superficial infections. By counterimmunoelectrophoresis, 10 of 10 isolates from deep infections were positive for polysaccharide, compared with 7 of 13 isolates from superficial infections (P = 0.02). All 23 strains tested were positive for polysaccharide when screened by immunodot. By enzyme immunoassay, the cross-reactive antigen produced by deep isolates (n = 9) had a mean titer of 1:5,500. In contrast, superficial isolates (n = 22) produced significantly less antigen than the deep isolates (P < 0.001), with a mean titer of 1:700. Isolates from environmental sources (n = 3) were similar to the superficial isolates, with a mean titer of 1:600. The mean concentrations +/- standard errors of cross-reactive polysaccharide released by deep isolates and superficial isolates were 3.09 +/- 0.44 and 1.74 +/- 0.30 micrograms/ml, respectively, when measured by rocket immunoelectrophoresis (P = 0.02). O-Acetyl epitopes were detected on polysaccharide from 8 of 9 strains of T. beigelii isolated from deep sources, while only 2 of 12 superficial isolates expressed detectable O-acetyl epitopes (P = 0.01). Thus, while all isolates of T. beigelii tested were capable of producing glucuronoxylomannan-like cross-reactive antigen, pathogenic isolates produced significantly more antigen than superficial or environmental isolates. Furthermore, significantly more pathogenic isolates than superficial or environmental isolates expressed antigen that was O acetylated.

Acetylation↗
PubMed1992

Antibodies elicited by a Cryptococcus neoformans-tetanus toxoid conjugate vaccine have the same specificity as those elicited in infection.

The antibody responses of BALB/c mice to serotype A Cryptococcus neoformans capsular polysaccharide (CNPS) were compared after cryptococcal infection and immunization with a serotype A glucuronoxylomannan-tetanus toxoid conjugate (GXM-TT). Infection rarely resulted in a rise of serum antibody titer to CNPS. In contrast, mice immunized with GXM-TT produced serum IgM and IgG to CNPS. Six IgM and one IgG1 monoclonal antibodies (MAbs) were generated from the spleen of one infected mouse. Nine IgM, 1 IgG3, 16 IgG1, and 7 IgA MAbs were generated from the spleen of one GXM-TT-immunized mouse. All MAbs generated from both mice bound to the GXM fraction of the capsular polysaccharide. For some MAbs, de-O-acetylation of serotype A GXM abolished or greatly reduced MAb binding compared with the native GXM. All MAbs reacted with CNPS from C. neoformans serotypes A-D. MAbs generated from the infected mouse competitively inhibited the binding of MAbs generated from the GXM-TT-immunized mouse. These results indicate that some antibodies elicited by infection with C. neoformans or by immunization with GXM-TT bind to the same antigenic determinant in the GXM.

Animals↗
PubMed1991

Antibodies to poly[(2----8)-alpha-N-acetylneuraminic acid] and poly[(2----9)-alpha-N-acetylneuraminic acid] are elicited by immunization of mice with Escherichia coli K92 conjugates: potential vaccines for groups B and C meningococci and E. coli K1.

Meningitis and other systemic infections caused by group B Neisseria meningitidis and Escherichia coli K1 remain important problems. The capsular polysaccharides (CPs) of these pathogens (poly[(2----8)-alpha-N-acetylneuraminic acid] or poly(alpha 2-8NeuNAc] are identical and are virulence factors and protective antigens for both. CP vaccines for these pathogens are not available because poly(alpha 2-8NeuNAc) alone, as a complex or a conjugate, is poorly immunogenic. Because oligomers of poly(alpha 2-8NeuNAc) in fetal brain and other tissues bind antibodies in vitro, it has been suggested that antibodies to this CP might be pathologic. We synthesized conjugates of this CP with tetanus toxoid under conditions that avoid lactone formation. Using this scheme, we also synthesized conjugates of group C meningococcal CP (poly[(2----9)-alpha-N-acetylneuraminic acid] or poly(alpha 2-9NeuNAc] and of E. coli K92 CP [poly(alpha 2-8, alpha 2-9NeuNAc)]. When injected s.c. in saline into mice, conjugates of poly(alpha 2-8NeuNAc) or poly(alpha 2-9NeuNAc) elicited homologous antibodies. E. coli K92 conjugates elicited both poly(alpha 2-8NeuNAc) and poly(alpha 2-9NeuNAc) antibodies. Both components of the conjugates expressed T-dependent immunologic properties under conditions and dosages acceptable for clinical evaluation. Poly(alpha 2-8NeuNAc) antibodies elicited by the homologous or the K92 conjugates had lower binding activities at 37 degrees C than at 22 degrees C. "Natural" poly(alpha 2-8NeuNAc) antibodies were present in almost all matched pairs of human maternal and cord sera; most cord levels were higher than in corresponding maternal sera. These findings suggest that increased levels of poly(alpha 2-8NeuNAc) IgG antibodies elicited by our conjugates will confer protective immunity to group B meningococci and E. coli K1 and will not be pathologic.

Animals↗
PubMed1991

Cockroaches (Blatta and Periplaneta species) as reservoirs of drug-resistant salmonellas.

A total of 221 cockroaches (Blatta and Periplaneta spp.), collected in hospitals, houses, animal sheds, grocery stores and restaurants, in various parts of South Kanara District, a south-west coastal region of India, were studied bacteriologically for the presence of various salmonellas. Salmonellas were isolated from 4.1% of these cockroaches. Nine strains of salmonellas were recovered, belonging to five serotypes--Salmonella bovismorbificans, S. oslo, S. typhimurium, S. mbandaka and S. braenderup, the former two being the commonest serotypes. All salmonellas were resistant to one or other of 11 antibacterial drugs used in the susceptibility test. Isolation of salmonellas from cockroaches collected from the livestock premises and human dwellings suggested that they may act as significant reservoirs of salmonella in nature. Recovery of serotypes, phage types and R-types that were commonly isolated from humans and animals of this locality, suggested a transmission role for cockroaches. By harbouring potentially pathogenic, drug-resistant salmonellas, these wandering arthropods may pose dangerous infective hazards to humans and animals.

Animals↗
PubMed1991

Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity.

We synthesized Cryptococcus neoformans serotype A glucuronoxylomannan (GXM) conjugate vaccines under conditions suitable for human use to prevent disseminated cryptococcosis. The purified, sonicated GXM was derivatized with adipic acid dihydrazide through either hydroxyl or carboxyl groups and then covalently bound to tetanus toxoid (TT) or Pseudomonas aeruginosa exoprotein A (rEPA). The immunogenicity of these conjugates was evaluated in BALB/c and general purpose mice by subcutaneous injection in saline. The conjugates elicited higher GXM antibody responses than GXM alone. Booster immunoglobulin G (IgG) and IgM responses were elicited by all conjugates in BALB/c mice. The conjugates prepared through hydroxyl activation (GXM-TT2 and GXM-rEPA) were more immunogenic than the one prepared through carboxyl activation (GXM-TT1). GXM antibody response was enhanced by the administration of monophosphoryl lipid A 2 days following the injection of GXM-TT2 (P less than 0.03). The conjugates also elicited IgG antibodies to the carrier proteins. Gel diffusion tests using conjugate-induced hyperimmune sera and chemically modified GXMs suggested that the specificity of GXM-TT1-induced antibodies was conferred by the O-acetyl groups. Hyperimmune sera generated by GXM-TT2 precipitated with the chemically unmodified and the de-O-acetylated GXMs but not with the carboxyl-reduced and de-O-acetylated GXM. GXM-TT2-induced hyperimmune serum also precipitated with the capsular polysaccharides of C. neoformans serotypes D, B, and C. The conjugate vaccines prepared through hydroxyl activation of the GXM are sufficiently immunogenic and appear to be suitable for clinical evaluation.

Animals↗
PubMed1991

Identity between polysaccharide antigens of Moraxella nonliquefaciens, group B Neisseria meningitidis, and Escherichia coli K1 (non-O acetylated).

A surface polysaccharide antigen of Moraxella nonliquefaciens, reported to be cross-reactive with the capsular polysaccharides of group B Neisseria meningitidis and Escherichia coli K1 (K. Błvre, K. Bryn, O. Closs, N. Hagen, and L. O. Froholm, NIPH Ann. 6:65-73, 1983), was isolated, purified, and characterized chemically, immunologically, and by nuclear magnetic resonance. This polysaccharide was shown to be a linear homopolymer of alpha (2----8)-linked N-acetylneuraminic acid, identical to the capsular polysaccharide of group B N. meningitidis and O-acetyl-negative variants of E. coli K1.

Animals↗