PMID- 24312662 OWN - NLM STAT- MEDLINE DCOM- 20150219 LR - 20211021 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 8 IP - 12 DP - 2013 TI - Immunogenicity of individual vaccine components in a bivalent nicotine vaccine differ according to vaccine formulation and administration conditions. PG - e82557 LID - 10.1371/journal.pone.0082557 [doi] LID - e82557 AB - Structurally distinct nicotine immunogens can elicit independent antibody responses against nicotine when administered concurrently. Co-administering different nicotine immunogens together as a multivalent vaccine could be a useful way to generate higher antibody levels than with monovalent vaccines alone. The immunogenicity and additivity of monovalent and bivalent nicotine vaccines was studied across a range of immunogen doses, adjuvants, and routes to assess the generality of this approach. Rats were vaccinated with total immunogen doses of 12.5-100 mug of 3'-aminomethyl nicotine conjugated to recombinant Pseudomonas exoprotein A (3'-AmNic-rEPA), 6-carboxymethylureido nicotine conjugated to keyhole limpet hemocyanin (6-CMUNic-KLH), or both. Vaccines were administered s.c. in alum or i.p. in Freund's adjuvant at matched total immunogen doses. When administered s.c. in alum, the contributions of the individual immunogens to total nicotine-specific antibody (NicAb) titers and concentrations were preserved across a range of doses. Antibody affinity for nicotine varied greatly among individuals but was similar for monovalent and bivalent vaccines. However when administered i.p. in Freund's adjuvant the contributions of the individual immunogens to total NicAb titers and concentrations were compromised at some doses. These results support the possibility of co-administering structurally distinct nicotine immunogens to achieve a more robust immune response than can be obtained with monovalent immunogens alone. Choice of adjuvant was important for the preservation of immunogen component activity. FAU - Cornish, Katherine E AU - Cornish KE AD - Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota, United States of America ; Minneapolis Medical Research Foundation, Minneapolis, Minnesota, United States of America. FAU - de Villiers, Sabina H L AU - de Villiers SH FAU - Pravetoni, Marco AU - Pravetoni M FAU - Pentel, Paul R AU - Pentel PR LA - eng GR - R01 DA010714/DA/NIDA NIH HHS/United States GR - T32 DA007097/DA/NIDA NIH HHS/United States GR - DA07097/DA/NIDA NIH HHS/United States GR - DA10714/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20131202 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adjuvants, Immunologic) RN - 0 (NicVAX) RN - 0 (Vaccines) RN - 6M3C89ZY6R (Nicotine) RN - 9013-72-3 (Hemocyanins) RN - FV4Y0JO2CX (keyhole-limpet hemocyanin) SB - IM MH - Adjuvants, Immunologic MH - Animals MH - Antibody Formation/immunology MH - Hemocyanins/metabolism MH - Male MH - Nicotine/*immunology MH - Rats MH - Rats, Sprague-Dawley MH - Vaccines/immunology/metabolism PMC - PMC3846984 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2013/12/07 06:00 MHDA- 2015/02/20 06:00 PMCR- 2013/12/02 CRDT- 2013/12/07 06:00 PHST- 2013/07/24 00:00 [received] PHST- 2013/10/24 00:00 [accepted] PHST- 2013/12/07 06:00 [entrez] PHST- 2013/12/07 06:00 [pubmed] PHST- 2015/02/20 06:00 [medline] PHST- 2013/12/02 00:00 [pmc-release] AID - PONE-D-13-30595 [pii] AID - 10.1371/journal.pone.0082557 [doi] PST - epublish SO - PLoS One. 2013 Dec 2;8(12):e82557. doi: 10.1371/journal.pone.0082557. eCollection 2013.