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Homogeneous Glycoconjugate Produced by Combined Unnatural Amino Acid Incorporation and Click-Chemistry for Vaccine Purposes
Published on: December 19, 2020
Immunological properties of complex conjugates based on Vibrio cholerae O1 Ogawa lipopolysaccharide antigen
E Paulovicová1, E Machová, A Hostacká
1Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic. chemempa@savba.sk
Abstract:
Host 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.
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