Investigating Hapten Clustering as a Strategy to Enhance Vaccines against Drugs of Abuse

Collins, Karen; Janda, Kim D.

doi:10.1021/bc500016k

Cited by 42 publications

(39 citation statements)

References 29 publications

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“…The increased hapten density from NKLP-A to NKLP-I verified the feasibility of modulating the Nic hapten density by changing the molar ratios of hapten to KLH in the preparation process. To date, most reported hapten-protein conjugate nicotine vaccines have hapten density ranging from 2 to 100 per protein molecule,[10, 37, 38] depending on the available lysine groups and conjugate chemistry. Noticeably, the design of the hybrid-NP based nicotine nanovaccine significantly increased the epitope numbers per particle over conventional conjugate nicotine vaccines, potentially contributing to an enhanced epitope recognition by B cells.…”

Section: Resultsmentioning

confidence: 99%

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

Zhao

Powers

et al. 2017

Biomaterials

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Although vaccination is a promising way to combat nicotine addiction, most traditional hapten-protein conjugate nicotine vaccines only show limited efficacy due to their poor recognition and uptake by immune cells. This study aimed to develop a hybrid nanoparticle-based nicotine vaccine with improved efficacy. The focus was to study the impact of hapten density on the immunological efficacy of the proposed hybrid nanovaccine. It was shown that the nanovaccine nanoparticles were taken up by the dendritic cells more efficiently than the conjugate vaccine, regardless of the hapten density on the nanoparticles. At a similar hapten density, the nanovaccine induced a significantly stronger immune response against nicotine than the conjugate vaccine in mice. Moreover, the high- and medium-density nanovaccines resulted in significantly higher anti-nicotine antibody titers than their low-density counterpart. Specifically, the high-density nanovaccine exhibited better immunogenic efficacy, resulting in higher anti-nicotine antibody titers and lower anti-carrier protein antibody titers than the medium- and low-density versions. The high-density nanovaccine also had the best ability to retain nicotine in serum and to block nicotine from entering the brain. These results suggest that the hybrid nanoparticle-based nicotine vaccine can elicit strong immunogenicity by modulating the hapten density, thereby providing a promising next-generation immunotherapeutic strategy against nicotine addiction.

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Section: Resultsmentioning

confidence: 99%

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

Zhao

Powers

et al. 2017

Biomaterials

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“…We note that the relative affinities for each drug-hapten-vaccine candidate as reported in Table 1 were modest (micomolar). However, we attribute this to the competition ELISA format, which greatly underestimates relative affinity for antibody-small molecule interactions (Collins and Janda, 2014). …”

Section: Resultsmentioning

confidence: 99%

Active vaccination attenuates the psychostimulant effects of α-PVP and MDPV in rats

Nguyen¹,

Bremer

Ducime

et al. 2017

Neuropharmacology

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Recreational use of substituted cathinones continues to be an emerging public health problem in the United States; cathinone derivatives α-pyrrolidinopentiophenone (α-PVP) and 3,4-methylenedioxypyrovalerone (MDPV), which have been linked to human fatalities and show high potential for abuse liability in animal models, are of particular concern. The objective of this study was to develop an immunotherapeutic strategy for attenuating the effects of α-PVP and MDPV in rats, using drug-conjugate vaccines created to generate antibodies with neutralizing capacity. Immunoconjugates (α-PVP-KLH and MDPV-KLH) or the control carrier protein, keyhole limpet hemocyanin (KLH), were administered to groups (N=12) of male Sprague-Dawley rats on Weeks 0, 2 and 4. Groups were administered α-PVP or MDPV (0.0, 0.25, 0.5, 1.0, 5.0 mg/kg, i.p.) in acute drug challenges and tested for changes in wheel activity. Increased wheel activity produced by α-PVP or MDPV in the controls was attenuated in the α-PVP-KLH and MDPV-KLH vaccinated groups, respectively. Rectal temperature decreases produced by MDPV in the controls were reduced in duration in the MDPV-KLH vaccine group. A separate group (N=19) was trained to intravenously self-administer α-PVP (0.05, 0.1 mg/kg/inf) and vaccinated with KLH or α-PVP-KLH, post-acquisition. Self-administration in α-PVP-KLH rats was initially higher than in the KLH rats but then significantly decreased following a final vaccine booster, unlike the stable intake of KLH rats. The data demonstrate that active vaccination provides functional protection against the effects of α-PVP and MDPV, in vivo, and recommend additional development of vaccines as potential therapeutics for mitigating the effects of designer cathinone derivatives.

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“…[11–14] However, none of them have shown overall enhanced smoking cessation rate over placebo so far, mainly due to the highly-varying and insufficient antibody titers. [15–17] Although great efforts have been made to improve their immunogenicity by modulating multiple factors, [13, 18–23] conjugate nicotine vaccines bear some intrinsic shortfalls, such as fast degradation, low nicotine loading capacity, low bioavailability, and poor recognition and uptake by immune cells, largely limiting their immunological efficacy.…”

Section: Introductionmentioning

confidence: 99%

Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization

Zhao

Harmon

et al. 2017

Biomaterials

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A lipid-polymeric hybrid nanoparticle-based next-generation nicotine nanovaccine was rationalized in this study to combat nicotine addiction. A series of nanovaccines, which had nicotine-haptens localized on carrier protein (LPKN), nanoparticle surface (LPNK), or both (LPNKN), were designed to study the impact of hapten localization on their immunological efficacy. All three nanovaccines were efficiently taken up and processed by dendritic cells. LPNKN induced a significantly higher immunogenicity against nicotine and a significantly lower anti-carrier protein antibody level compared to LPKN and LPNK. Meanwhile, it was found that the anti-nicotine antibodies elicited by LPKN and LPNKN bind nicotine stronger than those elicited by LPKN, and LPNK and LPNKN resulted in a more balanced Th1-Th2 immunity than LPKN. Moreover, LPNKN exhibited the best ability to block nicotine from entering the brain of mice. Collectively, the results demonstrated that the immunological efficacy of the hybrid nanoparticle-based nicotine vaccine could be enhanced by modulating hapten localization, providing a promising strategy to combatting nicotine addiction.

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Investigating Hapten Clustering as a Strategy to Enhance Vaccines against Drugs of Abuse

Cited by 42 publications

References 29 publications

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

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

Active vaccination attenuates the psychostimulant effects of α-PVP and MDPV in rats

Rationalization of a nanoparticle-based nicotine nanovaccine as an effective next-generation nicotine vaccine: A focus on hapten localization

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