Immunogenic properties of octasaccharide-protein conjugates derived from Klebsiella serotype 11 capsular polysaccharide

Zigterman, J. W. J.; Dam, J.E.G. van; Snippe, H.; Rotteveel, F. T. M.; Jansze, M.; Willers, J. M. N.; Kamerling, J.P.; Vliegenthart, Johannes F.G.

doi:10.1128/iai.47.2.421-428.1985

Cited by 22 publications

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References 33 publications

(58 reference statements)

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“…The enhanced immunogenicity of Pn12F as a component of a conjugate has been demonstrated for other uronic acid-containing CP, including the Vi of S. typhi, pneumococcus type 3, group C meningococci, and Klebsiella pneumoniae type 11 in laboratory animals (3,10,28,30). Recently, we have demonstrated this enhancement for conjugates of Staphylococcus aureus types 5 and 8 CP in mice when the synthetic scheme designed for the Vi and the Pn12F was used (9a, 27, 28).…”

Section: Discussionmentioning

confidence: 89%

Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae type 12F polysaccharide alone or conjugated to diphtheria toxoid

et al. 1990

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Conjugates of an uronic acid-containing capsular polysaccharide (CP), pneumococcous type 12F (Pn12F) bound to diphtheria toxoid (DT), were studied for safety and immunogenicity in adult volunteers. In mice, these conjugates, prepared with the same lot of DT and Pnl2F-40234-006, a homogenous CP of high molecular weight, or Pnl2-812408, a polydisperse CP with lower-molecular-weight material, were more immunogenic than the Pnl2F alone and had T-cell dependent properties (Infect. Immun. 56:2292Immun. 56: -2298Immun. 56: , 1988. Adult volunteers, randomized into three groups, were injected either with one of these two conjugates or with Pnu-Imune, the 23 valent pneumococcus vaccine containing 25 ,ug of Pn12F as one of its components.Volunteers were injected two times, 4 weeks apart, with the Pnl2F-DT conjugates and once with the Pnu-Imune. Side reactions following injection of the conjugates or Pnu-Imune were mild and short-lived. At 4 weeks and at 7 months after the first injection, higher levels of Pnl2F antibodies were found in the volunteers injected with the conjugates than in the Pnu-Imune group (P < 0.001). The conjugate prepared with the higher-molecular-weight Pnl2F elicited higher levels of antibodies than the conjugate prepared with a lower-molecular-weight Pn12F preparation (P = 0.05). Both conjugates elicited about a 13-fold rise in DT antibodies.

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Section: Discussionmentioning

confidence: 89%

Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae type 12F polysaccharide alone or conjugated to diphtheria toxoid

et al. 1990

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“…The immunological character of bacterial polysaccharides, which are thymus-independent antigens (5,39) can be changed by coupling (oligo)saccharides, as the antigenic determinant, to protein carriers (10,16,29). The conversion of the nature of the antigen from TI to thymus dependent is considered to be beneficial for the use of these antigens in a vaccine (11), since TD antigens induce immunological memory (2,3,20,39) and therefore provide long-lasting protection (29). Furthermore, native polysaccharides are not able to induce protective immune responses in young individuals (8), which gives rise to serious problems in individuals who are exposed to an increased risk of infection with Streptococcus species, Haemophilus influenzae, and Neisseria mengitidis (15,18).…”

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confidence: 99%

“…On the other hand, oligosaccharideprotein conjugates are able to induce protective antibody responses in young individuals (2,6,13,20). In previous studies, it was demonstrated that Streptococcus pneumoniae-and Klebsiella-derived oligosaccharides coupled to bovine serum albumin (BSA) and keyhole limpet hemocyanin (KLH) induce capsular polysaccharide-specific antibodies in mice (29,39). Furthermore, these studies indicated that BSA conjugates in general were less immunogenic than KLH conjugates (29,39).…”

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confidence: 99%

“…In previous studies, it was demonstrated that Streptococcus pneumoniae-and Klebsiella-derived oligosaccharides coupled to bovine serum albumin (BSA) and keyhole limpet hemocyanin (KLH) induce capsular polysaccharide-specific antibodies in mice (29,39). Furthermore, these studies indicated that BSA conjugates in general were less immunogenic than KLH conjugates (29,39). These studies prompted us to use BSA and KLH as the carrier in the studies presented here, since in our opinion BSA and KLH conjugates occupy extreme positions, with the former displaying weak and the latter strong immunogenicities (39).…”

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Nonionic block polymer surfactants modulate the humoral immune response against Streptococcus pneumoniae-derived hexasaccharide-protein conjugates

et al. 1989

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Nonionic block polymer surfactants (NBPs) were tested for the capacity to stimulate the antibody response against hexasaccharide (HS), derived from Streptococcus pneumoniae type 3 capsular polysaccharide (S3PS), which was conjugated to proteins. The immune response was evaluated in the (CBA/N x BALB/c)F1 progeny, in which female mice are phenotypically normal whereas male mice carry an X-chromosome-linked immunodeficiency. NBPs L101, L121, 1101, and 1501 were able to increase anti-HS immunoglobulin M (IgM) and IgG levels in both normal and X-chromosome-linked immunodeficient mice (with up to 74-fold stimulation of antibody titers). Distribution of S3PS-specific antibodies over the various IgG isotypes was restricted after immunization with either HS-bovine serum albumin or HS-keyhole limpet hemocyanin (HS-KLH). Addition of NBPs (in particular 1501) resulted in a more diverse immune response with either antigen as judged by isotype distribution. Isoelectric focusing of individual sera and subsequent detection of S3PS-binding antibodies in these sera by immunochemical staining revealed a restricted number of different spectrotypes in the course of the immune response. Upon immunization of mice with HS-KLH, spectra of secreted antibodies were slightly more complex and more densely stained than after immunization with HS-bovine serum albumin. Furthermore, NBPs 1101 and 1501 appeared to be able to stimulate the secretion of antibodies, which were secreted only in small amounts without the use of NBPs. Different explanations for increased spectrotype diversity after immunization with KLH as the carrier and after administration of NBPs as the adjuvant are discussed.

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Production of a Promising Biosynthetic Self‐Assembled Nanoconjugate Vaccine against Klebsiella Pneumoniae Serotype O2 in a General Escherichia Coli Host

Peng¹,

Wu²,

Wang³

et al. 2021

Advanced Science

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Klebsiella pneumoniae has emerged as a severe opportunistic pathogen with multiple drug resistances. Finding effective vaccines against this pathogen is urgent. Although O-polysaccharides (OPS) of K. pneumoniae are suitable antigens for the preparation of vaccines given their low levels of diversity, the low immunogenicity (especially serotype O2) limit their application. In this study, a general Escherichia coli host system is developed to produce a nanoscale conjugate vaccine against K. pneumoniae using the Nano-B5 self-assembly platform. The experimental data illustrate that this nanoconjugate vaccine can induce an efficient humoral immune response in draining lymph nodes (dLNs) and elicit high titers of the IgG antibody against bacterial lipopolysaccharide (LPS). The ideal prophylactic effects of these nanoconjugate vaccines are further demonstrated in mouse models of both systemic and pulmonary infection. These results demonstrate that OPS with low immunogenicity can be changed into an effective antigen, indicating that other haptens may be applicable to this strategy in the future. To the knowledge, this is the first study to produce biosynthetic nanoconjugate vaccines against K. pneumoniae in E. coli, and this strategy can be applied to the development of other vaccines against pathogenic bacteria.

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Immunogenic properties of octasaccharide-protein conjugates derived from Klebsiella serotype 11 capsular polysaccharide

Cited by 22 publications

References 33 publications

Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae type 12F polysaccharide alone or conjugated to diphtheria toxoid

Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae type 12F polysaccharide alone or conjugated to diphtheria toxoid

Nonionic block polymer surfactants modulate the humoral immune response against Streptococcus pneumoniae-derived hexasaccharide-protein conjugates

Production of a Promising Biosynthetic Self‐Assembled Nanoconjugate Vaccine against Klebsiella Pneumoniae Serotype O2 in a General Escherichia Coli Host

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