PMID- 18656557
OWN - NLM
STAT- MEDLINE
DCOM- 20090430
LR  - 20211020
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 8
IP  - 11
DP  - 2008 Nov
TI  - Enhanced immunogenicity of a bivalent nicotine vaccine.
PG  - 1589-94
LID - 10.1016/j.intimp.2008.07.001 [doi]
AB  - The efficacy of nicotine vaccines for smoking cessation is dependent upon their 
      ability to elicit sufficiently high serum antibody concentrations. This study 
      compared two nicotine immunogens representing different hapten presentations, 
      3'-aminomethyl nicotine conjugated to recombinant Pseudomonas exoprotein A 
      (3'-AmNic-rEPA) and 6-carboxymethlureido nicotine conjugated to keyhole limpet 
      hemocyanin (6-CMUNic-KLH), and assessed whether their concurrent administration 
      would produce additive serum antibody concentrations in rats. Effects of 
      vaccination on nicotine pharmacokinetics were also studied. Vaccination of rats 
      with these immunogens produced non cross-reacting nicotine-specific antibodies 
      (NicAb). Serum NicAb concentrations elicited by each individual immunogen were 
      not affected by whether the immunogens were administered alone as monovalent 
      vaccines or together as a bivalent vaccine. The total NicAb concentration in the 
      bivalent vaccine group was additive compared to that of the monovalent vaccines 
      alone. Higher serum NicAb concentrations, irrespective of which immunogen 
      elicited the antibodies, were associated with greater binding of nicotine in 
      serum, a lower unbound nicotine concentration in serum, and lower brain nicotine 
      concentration. These results demonstrate that it is possible to design immunogens 
      which provide distinct nicotine epitopes for immune presentation, and which 
      produce additive serum antibody levels. The concurrent administration of these 
      immunogens as a bivalent vaccine may provide a general strategy for enhancing the 
      antibody response to small molecules such as nicotine.
FAU - Keyler, D E
AU  - Keyler DE
AD  - Minneapolis Medical Research Foundation, Minneapolis, MN, United States.
FAU - Roiko, S A
AU  - Roiko SA
FAU - Earley, C A
AU  - Earley CA
FAU - Murtaugh, M P
AU  - Murtaugh MP
FAU - Pentel, P R
AU  - Pentel PR
LA  - eng
GR  - T32 DA007097/DA/NIDA NIH HHS/United States
GR  - P50-DA013333/DA/NIDA NIH HHS/United States
GR  - F31 DA021946/DA/NIDA NIH HHS/United States
GR  - DA10714/DA/NIDA NIH HHS/United States
GR  - P50 DA013333/DA/NIDA NIH HHS/United States
GR  - T32-DA07097/DA/NIDA NIH HHS/United States
GR  - R01 DA010714/DA/NIDA NIH HHS/United States
GR  - R01 DA010714-12/DA/NIDA NIH HHS/United States
GR  - P50 DA013333-100002/DA/NIDA NIH HHS/United States
GR  - F31-DA021946/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080724
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Proteins)
RN  - 0 (Vaccines, Conjugate)
RN  - 0 (pseudomonas exoprotein A protein, Pseudomonas aeruginosa)
RN  - 6M3C89ZY6R (Nicotine)
RN  - 9013-72-3 (Hemocyanins)
RN  - FV4Y0JO2CX (keyhole-limpet hemocyanin)
SB  - IM
MH  - Animals
MH  - Antigens, Bacterial/immunology
MH  - Bacterial Proteins/chemistry/*immunology
MH  - Cross Reactions/immunology
MH  - Hemocyanins/chemistry/*immunology
MH  - Nicotine/chemistry/*immunology
MH  - Rats
MH  - Smoking/*therapy
MH  - Smoking Cessation/*methods
MH  - *Vaccination
MH  - Vaccines, Conjugate/chemistry/immunology
PMC - PMC2577591
MID - NIHMS73081
EDAT- 2008/07/29 09:00
MHDA- 2009/05/01 09:00
PMCR- 2009/11/01
CRDT- 2008/07/29 09:00
PHST- 2008/03/05 00:00 [received]
PHST- 2008/06/30 00:00 [revised]
PHST- 2008/07/01 00:00 [accepted]
PHST- 2008/07/29 09:00 [pubmed]
PHST- 2009/05/01 09:00 [medline]
PHST- 2008/07/29 09:00 [entrez]
PHST- 2009/11/01 00:00 [pmc-release]
AID - S1567-5769(08)00202-6 [pii]
AID - 10.1016/j.intimp.2008.07.001 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2008 Nov;8(11):1589-94. doi: 10.1016/j.intimp.2008.07.001. 
      Epub 2008 Jul 24.