Immunological properties of complex conjugates based on Vibrio cholerae O1 Ogawa lipopolysaccharide antigen

Abstract

cš y¢ SummaryHost protection by humoral immunity against Vibrio cholerae O1 confers lipopolysaccharide (LPS)-specific vibriocidal antibodies. Levels of relevant specific antibodies are closely related to complement-mediated inactivation of the vibrios inoculum, especially on the mucosal surface of intestine. We have tested complex V. cholerae O1 Ogawa-detoxified lipopolysaccharide (dLPS) conjugates. The first conjugate contained glucan both as the immunomodulator and the matrix; the second conjugate contained immunologically inert amylose as matrix. Both d-LPS conjugates contain multiply attached dLPS antigen. These conjugates elicited a statistically significant increase of antigen-specific IgG levels in mice ( P < < < < 0·001 and P < < < < 0·05, respectively). The specific anti-conjugate IgG and IgA response after the second (booster) dose were significantly higher compared to pre-immune and whole-cell response. The most effective vibriocidal activity was observed in the case of conjugate, with glucan as the matrix. The highest correlation was found between vibriocidal activity and specific IgG2b ( r = = = = 0·765) and IgA ( r = = = = 0·887) sera levels. The determination of specific IgG subclasses and IgG2a + + + + 2b/IgG1 ratio revealed a dominant T H 1 cell response crucial for effective vaccine candidate.

Immunomodulative properties of conjugates composed of detoxified lipopolysaccharide and capsular polysaccharide of Vibrio cholerae O135 bound to BSA-protein carrier

“…1). The binding of dLPS to polymer matrix ensured the large amount of the antigen in conjugate since the density of the epitope attachment is crucial for effective activation of the immune system (Paulovičová et al 2006).…”

“…Chemical conjugation of the saccharide moiety to peptide (Alexander et al 2004) or protein carrier mediates the induction of the T-cell-dependent immune response to saccharide epitopes (Robbins et al 1995). Efficient T-celldependent response is manifested by the effective switch of specific IgM isotype antibodies to IgG and IgA, and long-term B cell memory function (Paulovičová et al 2006).…”

Investigation towards bivalent chemically defined glycoconjugate immunogens prepared from acid-detoxified lipopolysaccharide of Vibrio cholerae O1, serotype Inaba

“…In contrast, sera induced in mice immunized with the Inaba conjugates, including those incorporating a hexasaccharide hapten, recognize the LPS from both serotypes, but are not protective [20]. Other attempts to develop a V. cholerae O1 vaccine have relied on the use of alkali or hydrazine-detoxified LPS [21][22][23][24][25] and the various preparations proved to be immunogenic in mice or rabbits. Nevertheless, Inaba conjugates failed to elicit a sufficient level of protection in humans during a phase 1 clinical evaluation [26].…”

Immunomodulation of T-cell responses withVibrio choleraeO135 capsular polysaccharide and its protein conjugate, novel cholera vaccine study models

“…We have previously revealed the novel structure of V. cholerae O1 lipopolysaccharide‐derived glycoconjugates (Machová et al ., ) and the immunological efficacy of subcellular preparations of vibrios (Paulovičová et al ., , , b; Korcová et al ., ). Here we report the results of in vivo studies on T‐cell immunobiological effectivity of V. cholerae O135 CPS and its conjugate, a possible model structure for cholera vaccine.…”