TLR3 and TLR7/8 agonists improve immunization outcome in nicotine exposed mice through different mechanisms

Nouri-Shirazi, Mahyar; Guinet, Elisabeth

doi:10.1016/j.imlet.2022.05.002

Cited by 3 publications

(1 citation statement)

References 52 publications

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“…Another effective approach for improving vaccine efficacy is adopting immune adjuvants that could stimulate the immune system. Besides traditional aluminum salts, many immunostimulants, such as CpG, MPL, Poly(I:C), etc., [3][4][5][6][7][8][9][10] were investigated for their enhancement function on immunization outcomes in anti-nicotine vaccine studies. It was proven that these adjuvants could undeniably improve the promotion of the secretion of antibodies and immunological cell factors, but the functions varied greatly by case.…”

Section: Introductionmentioning

confidence: 99%

Unfolding Protein-Based Hapten Coupling via Thiol–Maleimide Click Chemistry: Enhanced Immunogenicity in Anti-Nicotine Vaccines Based on a Novel Conjugation Method and MPL/QS-21 Adjuvants

Xu,

Li,

Meng

et al. 2024

Polymers

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Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol–maleimide “click” chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine–BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants.

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