Nicotine conjugate vaccine efficacy is limited by the concentration of nicotine-specific antibodies that can be reliably generated in serum. Previous studies suggest that the concurrent use of 2 structurally distinct nicotine immunogens in rats can generate additive antibody responses by stimulating distinct B cell populations. In the current study we investigated whether it is possible to identify a third immunologically distinct nicotine immunogen. The new 1′-SNic immunogen (2S)-N,N′-(disulfanediyldiethane-2,1-diyl)bis[4-(2-pyridin-3-ylpyrrolidin-1-yl)butanamide] conjugated to keyhole limpet hemocyanin (KLH) differed from the existing immunogens 3′-AmNic-rEPA and 6-CMUNic-BSA in linker position, linker composition, conjugation chemistry, and carrier protein. Vaccination of rats with 1′-SNic-KLH elicited high concentrations of high affinity nicotine-specific antibodies. The antibodies produced in response to 1′-SNic-KLH did not appreciably cross-react in ELISA with either 3′-AmNic-rEPA or 6-CMUNic-BSA or vice-versa, showing that the B cell populations activated by each of these nicotine immunogens were non-overlapping and distinct. Nicotine retention in serum was increased and nicotine distribution to brain substantially reduced in rats vaccinated with 1′-SNic-KLH compared to controls. Effects of 1′-SNic-KLH on nicotine distribution were comparable to those of 3′-AmNic-rEPA which has progressed to late stage clinical trials as an adjunct to smoking cessation. These data show that it is possible to design multiple immunogens from a small molecule such as nicotine which elicit independent immune responses. This approach could be applicable to other addiction vaccines or small molecule targets as well.
Objective:This study assessed renters’ preferences for official smoking policies in their buildings and their practices concerning restricting tobacco smoking in their apartments.Design:Renters (n = 301) living in large apartment complexes in a suburb of Minneapolis, Minnesota, completed a mail survey.Main outcome measures:The survey asked about the official smoking policies in place in their apartment buildings, their preferences for policies, whether they had smelled tobacco smoke coming into their apartments from without, and, if so, what they had done about it.Results:The majority of non-smokers (79%) preferred that their building be smoke-free. When asked to identify the current smoking policy in their buildings, residents disagreed substantially. Most renters (60%) reported smoke-free policies in their own apartments and another significant proportion (23%) restricted smoking to certain areas or occasions or persons. 75% thought that enforcing a smoke-free policy for guests would not be difficult. 53% of those in non-smoking households had smelled tobacco smoke in their apartments; most of these reported being bothered by it. However, very few complained to the building owner or manager (15.5%) or to the smoker (6.9%).Conclusions:The majority of non-smokers preferred that their buildings be smoke-free. A failure to report problems to apartment managers might be an impediment to instituting smoke-free policies in apartment buildings. The considerable disagreement among residents within apartment complexes about the current official smoking policy in their buildings suggests that policies are lacking or are not well communicated.
Prescription opioids abuse and associated deaths are an emerging concern in the USA. Vaccination against prescription opioids may provide an alternative to pharmacotherapy. An oxycodone hapten containing a tetraglycine linker at the C6 position (6OXY(Gly) 4 OH) conjugated to keyhole limpet hemocyanin (KLH) has shown early proof-of-efficacy in rodents as a candidate immunogen (6OXY(Gly) 4 -KLH) for the treatment of oxycodone abuse. In this study, oxycodonebased and hydrocodone-based haptens were conjugated to KLH to generate immunogens that would recognize both oxycodone and hydrocodone. Vaccination with 6OXY(Gly) 4 -KLH increased drug binding in serum, reduced drug distribution to brain, and blunted analgesia for both
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