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Vaccines 2017, 5(2), 11; doi:10.3390/vaccines5020011

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

1
Pfizer Biotherapeutics Pharmaceutical Sciences, Chesterfield, MO 63017, USA
2
Pfizer Vaccine Immunotherapeutics, Ottawa Laboratories, Ottawa, ON K2K 3A2, Canada
Present address: Abbott Point of Care, 185 Corkstown Rd, Nepean, Ottawa, ON K2H 8V4, Canada.
Present address: Seqirus, 29 Market Street, Maidenhead SL6 BAA, UK.
§
Present address: Human Health Therapeutics, National Research Council of Canada, Ottawa, ON K1A 0R6, Canada.
*
Author to whom correspondence should be addressed.
Academic Editor: Alfredo G. Torres
Received: 28 March 2017 / Revised: 3 May 2017 / Accepted: 11 May 2017 / Published: 17 May 2017
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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 conjugates with a more closed structure than those with an open conformation. These studies highlight the need for a better understanding of the physicochemical properties of small molecule conjugate vaccines. View Full-Text
Keywords: anti-nicotine vaccine; cross-reactive material 197 (CRM197); smoking cessation; conjugation; Ab titer; Ab avidity anti-nicotine vaccine; cross-reactive material 197 (CRM197); smoking cessation; conjugation; Ab titer; Ab avidity
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Thorn, J.M.; Bhattacharya, K.; Crutcher, R.; Sperry, J.; Isele, C.; Kelly, B.; Yates, L.; Zobel, J.; Zhang, N.; Davis, H.L.; McCluskie, M.J. The Effect of Physicochemical Modification on the Function of Antibodies Induced by Anti-Nicotine Vaccine in Mice. Vaccines 2017, 5, 11.

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