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
Sep 24, 1985·Biochemistry·M G BlewittE London
Apr 1, 1984·Clinical Pharmacology and Therapeutics·N L Benowitz, P Jacob
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·M J BennettD Eisenberg
Apr 20, 2001·Vaccine·B BolgianoM J Corbel
Dec 18, 2003·Addiction·John R HughesShelly Naud
Feb 19, 2004·European Journal of Immunology·Jörg VollmerArthur M Krieg
Dec 13, 2006·Vaccine·Mario Landys Chovel CuervoVicente Perdomo
Apr 2, 2008·Vaccine·Angela BardottiPaolo Costantino
Jun 17, 2008·Lancet·Dorothy K HatsukamiPrakash C Gupta
Mar 21, 2012·Proceedings of the National Academy of Sciences of the United States of America·Enrico MalitoGlen Spraggon
Jan 25, 2013·Scientific Reports·Huimin TongGang Ren
Apr 9, 2013·International Immunopharmacology·Michael J McCluskieHeather L Davis
Oct 8, 2013·PloS One·David C PrydeMichael J McCluskie
Dec 3, 2014·Vaccine·S PecettaUNKNOWN Study Group
Mar 5, 2015·International Immunopharmacology·Michael J McCluskieHeather L Davis
Sep 26, 2015·International Immunopharmacology·Michael J McCluskieHeather L Davis
Mar 15, 2016·Bioconjugate Chemistry·Kyle TotaroBradley Lether Pentelute
May 29, 2016·Journal of Pharmaceutical Sciences·Eugene VidunasJustin Moran
Citations
Aug 24, 2019·PloS One·Nya L FraleighHoang-Thanh Le
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
Feb 7, 2021·Vaccines·Nya L FraleighHoang-Thanh Le
May 20, 2021·Journal of the American Society for Mass Spectrometry·Cedric E BobstIgor A Kaltashov
Sep 22, 2018·Molecular Pharmaceutics·Federico BaruffaldiMarco Pravetoni
Nov 27, 2018·Bioconjugate Chemistry·Jake JaffeMatthew B Francis
Apr 25, 2019·Molecular Pharmaceutics·F BaruffaldiM Pravetoni