Molecular attributes of conjugate antigen influence function of antibodies induced by anti-nicotine vaccine in mice and non-human primates

McCluskie, Michael J.; Thorn, Jennifer M.; Mehelic, Paul; Kolhe, Parag; Bhattacharya, Keshab; Finneman, Jari I.; Stead, David R.; Piatchek, Michele Bailey; Zhang, Ningli; Chikh, Ghania; Cartier, Janna; Evans, Dana M.; Merson, James; Davis, Heather L.

doi:10.1016/j.intimp.2015.02.030

Cited by 36 publications

(53 citation statements)

References 35 publications

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“…87 This impressive effort yielded a lead immunogen consisting of the 5-aminoethoxy-nicotine (Hapten 7) conjugated to CRM 197 . 87 The optimized NIC7-CRM 197 adsorbed on alum plus the toll-like receptor (TLR) 9 agonist CpG adjuvant showed promising pre-clinical efficacy in both mice and NHP, 46,87,89 and these candidates were recently evaluated in a clinical trial ( Table 1). Analysis of several lots of NIC7-CRM 197 showed that higher vaccine immunogenicity and efficacy correlated to lower degree of conjugate aggregation, and minimal presence of adducts.…”

Section: Pre-clinical Developmentmentioning

confidence: 99%

“…Analysis of several lots of NIC7-CRM 197 showed that higher vaccine immunogenicity and efficacy correlated to lower degree of conjugate aggregation, and minimal presence of adducts. 89 Also, NIC7-CRM 197…”

Section: Pre-clinical Developmentmentioning

confidence: 99%

“…89 In summary, hapten chemistry, linker composition and position, bioconjugation chemistry, hapten load, and conjugate purity are important parameters that affect immunogenicity and efficacy of vaccines for SUD.…”

Section: Pre-clinical Developmentmentioning

confidence: 99%

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Section: Pre-clinical Developmentmentioning

confidence: 99%

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“…Based on Ab titers, affi nity, and function (using the radiolabeled nicotine challenge model in mouse), 5-amino-ethoxynicotine was selected and further used with the DT carrier to evaluate the infl uence of linker polarity, rigidity, and length on immunogenicity . High Ab concentrations and nicotine binding effi ciencies were reported in mice and nonhuman primates McCluskie et al 2013McCluskie et al , 2015. In the latest study 27 variants of a candidate vaccine, now designated NIC7-CRM, were evaluated (McCluskie et al 2015 ).…”

Section: Non-particulate Nicotine Vaccines In Clinical Developmentmentioning

confidence: 99%

“…High Ab concentrations and nicotine binding effi ciencies were reported in mice and nonhuman primates McCluskie et al 2013McCluskie et al , 2015. In the latest study 27 variants of a candidate vaccine, now designated NIC7-CRM, were evaluated (McCluskie et al 2015 ). (Tonstad et al 2013 ).…”

Section: Non-particulate Nicotine Vaccines In Clinical Developmentmentioning

confidence: 99%

Nanoparticle-Based Nicotine Vaccine

Ilyinskii

Johnston

2015

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Immunogenicity of a peptide‐based anti‐IgE conjugate vaccine in non‐human primates

Weeratna

Chikh

Zhang

et al. 2016

Immunity Inflam & Disease

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The anti‐human immunoglobulin E (IgE) monoclonal antibody, omalizumab (Xolair®, Genentech, South San Fransisco, CA), is effective in the treatment of poorly controlled moderate to severe allergic asthma and chronic idiopathic urticaria. It acts by specifically binding to the constant domain (Cϵ3) of free human IgE in the blood and interstitial fluid. Although efficacious, use of omalizumab is limited due to restrictions on patient weight and pre‐existing IgE levels, and frequent dosing (q2–4 weeks). A vaccine inducing anti‐IgE antibodies has the potential for similar clinical benefits with less frequent dosing and relatively lower cost of goods. We developed a vaccine containing two IgE peptide‐conjugates targeting the Cϵ3 domain of human IgE. As part of preclinical evaluation of the vaccine to optimize formulation and dose prior to initiating clinical studies, we evaluated the vaccine in non‐human primates, and demonstrate the induction of anti‐peptide antibodies that can bind to conformationally intact human IgE and are capable, at least in some animals, of substantial lowering circulating IgE levels.

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Molecular attributes of conjugate antigen influence function of antibodies induced by anti-nicotine vaccine in mice and non-human primates

Cited by 36 publications

References 35 publications

Biologics to treat substance use disorders: Current status and new directions

Biologics to treat substance use disorders: Current status and new directions

Nanoparticle-Based Nicotine Vaccine

Immunogenicity of a peptide‐based anti‐IgE conjugate vaccine in non‐human primates

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