Effect of Adjuvant Release Rate on the Immunogenicity of Nanoparticle-Based Vaccines: A Case Study with a Nanoparticle-Based Nicotine Vaccine

Abstract

Adjuvants are a critical component for vaccines, especially for a poorly immunogenic antigen, such as nicotine. However, the impact of adjuvant release rate from a vaccine formulation on its immunogenicity has not been well illustrated. In this study, we fabricated a series of hybridnanoparticle-based nicotine vaccines to study the impact of adjuvant release rate on their immunological efficacy. It was found that the nanovaccine with a medium or slow adjuvant release rate induced a significantly higher anti-nicotine antibody titer than that with a fast release rate. Furthermore, the medium and slow adjuvant release rates resulted in a significantly lower brain nicotine concentration than the fast release rate after nicotine challenge. All findings suggest that adjuvant release rate affects the immunological efficacy of nanoparticle-based nicotine vaccines, providing a potential strategy to rationally designing vaccine formulations against psychoactive drugs or even other antigens. The hybrid-nanoparticle-based nicotine vaccine with an optimized adjuvant release rate can be a promising next-generation immunotherapeutic candidate against nicotine.

pH and ROS Responsiveness of Polymersome Nanovaccines for Antigen and Adjuvant Codelivery: An In Vitro and In Vivo Comparison

“…An inherent risk of using environmentally responsive NVs is the potential compromise of in vivo stability in circulation or in specific tissue environments. This could result in premature antigen and/or adjuvant release before DC uptake, which reduces the degree of synchronized codelivery of antigen and adjuvant. , This observation was reported by Zhao et al, evaluating the adjuvant release (R-848/MPLA) from PLGA NVs prepared from PLGA polymer with different inherent viscosities to obtain different antigen release kinetics. Because of the distinct release kinetics prior to being captured by antigen-presenting cells, a significant amount of adjuvant could be prematurely released from NVs that exhibit a rapid release rate.…”

Assessing Neutralized Nicotine Distribution Using Mice Vaccinated with the Mucosal Conjugate Nicotine Vaccine

“…Current parenteral and mucosal nicotine vaccines have been published with varying degrees of efficacy [13][14][15][16][17][18][30][31][32] and they all demonstrate significant levels of anti-nicotine antibodies that are able to block nicotine from entering the brain. Despite this similarity, the challenge and nicotine analysis methods vary and nicotine recovery tends to be low.…”

“…While effective, recently there has been a shift away from using [ 3 H]-nicotine for nicotine challenges, and towards using nicotine tartrate to assess the distribution of nicotine by GC/MS, LC/MS or HPLC. However, unlike [ 3 H]-nicotine, that is typically if not always delivered intravenously (IV), non-tritiated forms of nicotine have been delivered subcutaneously (SC) [13][14][15][16], IV [17], or intraperitoneally (IP) [18], all of which resulted in low levels of recovery, regardless of the dose administered. This does not necessarily permit nicotine vaccines evaluated in vivo to be properly assessed due to the low recovery rates in the brain and the sera.…”

Nanoparticle delivery systems for substance use disorder

“…To address these shortcomings, Zhao and colleagues developed a lipid-polymeric nanoparticle-based nicotine vaccine and found that it had improved cellular uptake by dendritic cells and immunogenicity in mice compared to conjugate vaccines [ 96 ]. In other preclinical studies, researchers demonstrated that the immunogenicity and pharmacokinetic efficacy of the nicotine nanovaccine, called NanoNicVac, could be improved by modulating the nanoparticle size, hapten density and localization, carrier proteins, adjuvants, and release rate [ 97 – 99 ] (Table 1 ). With these improvements, NanoNicVac was found to reduce brain levels of nicotine by 71% in mice [ 99 ].…”

“…In other preclinical studies, researchers demonstrated that the immunogenicity and pharmacokinetic efficacy of the nicotine nanovaccine, called NanoNicVac, could be improved by modulating the nanoparticle size, hapten density and localization, carrier proteins, adjuvants, and release rate [ 97 – 99 ] (Table 1 ). With these improvements, NanoNicVac was found to reduce brain levels of nicotine by 71% in mice [ 99 ]. Consistent with the previous studies in mice, the nicotine nanoparticle vaccine, SEL-068, effectively reduced the discriminative-stimulus effects of nicotine in nonhuman primates [ 100 ].…”