The Effect of Physicochemical Modification on the Function of Antibodies Induced by Anti-Nicotine Vaccine in Mice

Vaccines
Jennifer M ThornMichael J McCluskie

Abstract

Smoking remains one of the major causes of morbidity and mortality worldwide. One approach to assisting smoking cessation is via anti-nicotine vaccines, composed of nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). We have previously shown that the carrier, hapten, linker, hapten load, degree of conjugate aggregation, and presence of adducts can each influence the function (nicotine-binding capacity) of the antibody (Ab) induced. Herein, we extend those findings and show that tertiary structure is also critical to the induction of functional immune responses and that this can be influenced by conjugation conditions. We evaluated immunogenicity in mice using six lots of NIC7-CRM, a conjugate of 5-aminoethoxy-nicotine (Hapten 7), and a single point (glycine 52 to glutamic acid) mutant nontoxic form of diphtheria toxin, cross-reactive material 197 (CRM197), which were synthesized under different reaction conditions resulting in conjugates with equivalent molecular characteristics (hapten load, aggregates, adducts), but a different tertiary structure. When tested in mice, better functional responses (reduced nicotine in the brain of immunized animals relative to non-immunized controls) were obtained with conju...Continue Reading

References

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Mar 21, 2012·Proceedings of the National Academy of Sciences of the United States of America·Enrico MalitoGlen Spraggon
Mar 15, 2016·Bioconjugate Chemistry·Kyle TotaroBradley Lether Pentelute
May 29, 2016·Journal of Pharmaceutical Sciences·Eugene VidunasJustin Moran

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Citations

Jul 1, 2020·Immunological Reviews·Virgil SchijnsEd C Lavelle
Jul 26, 2019·NPJ Vaccines·David F ZeiglerChristopher H Clegg
Mar 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hoang-Thanh LeAlexandrine L Martel
Nov 27, 2018·Bioconjugate Chemistry·Jake JaffeMatthew B Francis

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Methods Mentioned

BETA
Protein Assay
Electrophoresis
ELISA

Software Mentioned

GraphPad
Sedfit
GraphPad Prism

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