Immunogenicity of Individual Vaccine Components in a Bivalent Nicotine Vaccine Differ According to Vaccine Formulation and Administration Conditions

Abstract

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 μg 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.

The frequency of early-activated hapten-specific B cell subsets predicts the efficacy of vaccines for nicotine dependence

“…0.03 mg/kg nicotine compared to KLH. In rats, the quantity and quality of the anti-nicotine antibody response, and the magnitude of immunization effect in blocking nicotine distribution to the brain depended upon route of immunization and adjuvant [34,40,41]. In rats, i.p.…”

Conjugate Vaccine Immunotherapy for Substance Use Disorder

“…Simultaneous immunization of multiple hapten protein conjugates with distinct hapten structures has been explored (Keyler et al, 2008;Pravetoni et al, 2012a;Cornish et al, 2013;de Villiers et al, 2013). In these studies, the hapten linkers were installed at different positions on the nicotine molecule to presumably produce distinct B cell populations specific to each hapten.…”

“…Conjugate Vaccine Immunotherapy for Substance Use Disorder effective (McCluskie et al, 2015a). An assessment of KLH and rEPA as carriers has revealed higher antinicotine antibody concentrations when vaccinating with the KLH conjugate, although different haptens on each carrier were used (Cornish et al, 2013). Another protein derived from the cholera B toxin (rCTB) has been used in a cocaine vaccine, which has been tested with limited success in clinical trials (phases I-III) (Kosten et al, 2002(Kosten et al, , 2014Martell et al, 2005).…”

Engineering of a hybrid nanoparticle-based nicotine nanovaccine as a next-generation immunotherapeutic strategy against nicotine addiction: A focus on hapten density

“…A variety of approaches to strengthen the immunogenicity of traditional conjugate nicotine vaccines have been investigated, including the design of hapten structure,[16, 17] the modulation of the linker position and composition,[8] the selection of carrier proteins,[10] the use of different adjuvants,[18] the application of multivalent vaccines,[19–22] and the optimization of administration routes[23]. However, as the immune system is relatively poor at recognizing small soluble protein antigens [24, 25], traditional conjugate nicotine vaccines bear a serious innate shortcoming, poor recognition and internalization by immune cells.…”