Komla Essie, Abucayon Erwin G, Godin C Steven, Sulima Agnieszka, Jacobson Arthur E, Rice Kenner C, Matyas Gary R
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Center for Military Infectious Diseases Research, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA.
Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.
Vaccines (Basel). 2025 Jul 26;13(8):792. doi: 10.3390/vaccines13080792.
: Opioid use disorder (OUD) remains a severe health problem globally, resulting in substantial social and economic challenges. While existing medications for managing OUD are proven to be effective, they also present certain challenges. A vaccine offers a promising therapeutic strategy to combat OUD and potentially reduce the risk of overdose death. The TT-6-AmHap heroin conjugate vaccine has effectively reduced heroin-induced pharmacological effects in behavioral assays as well as demonstrated the induction of high titer and high affinity antibody responses in mice and rats. In this GLP study conducted in rabbits, the potential local and systemic toxicity of the TT-6-AmHap heroin vaccine in combination with or without adjuvants ALF43 and Alhydrogel (ALFA) was investigated. : Male and female New Zealand White rabbits were administered with vaccines or a saline control intramuscularly at two-week intervals over a 57-day study period. The presence, persistence or reversibility of any toxic effects of the vaccine was determined over a four-week recovery period. : Administration of TT-6-AmHap with or without the adjuvants induced high antibody-specific IgG in treatment groups compared to the controls. The study found no TT-6-AmHap-related effects on mortality, physical examinations, dermal Draize observations, body weights, body weight changes, food consumption, ophthalmology, clinical pathology (hematology, coagulation, clinical chemistry, and urinalysis), macroscopic pathology, or organ weights. : Under the conditions of this study, these results demonstrate that the TT-6-AmHap vaccine with or without adjuvants was well tolerated, immunogenic, and the effects were not considered adverse in both male and female rabbits.
阿片类物质使用障碍（OUD）在全球范围内仍然是一个严重的健康问题，带来了巨大的社会和经济挑战。虽然现有的用于管理OUD的药物已被证明是有效的，但它们也存在某些挑战。疫苗为对抗OUD和潜在降低过量死亡风险提供了一种有前景的治疗策略。TT-6-AmHap海洛因缀合疫苗在行为学试验中有效降低了海洛因诱导的药理作用，并且在小鼠和大鼠中证明了可诱导高滴度和高亲和力的抗体反应。在这项在兔子身上进行的GLP研究中，研究了TT-6-AmHap海洛因疫苗联合或不联合佐剂ALF43和氢氧化铝（ALFA）的潜在局部和全身毒性。在为期57天的研究期间，每隔两周给雄性和雌性新西兰白兔肌肉注射疫苗或生理盐水对照。在四周的恢复期内确定疫苗任何毒性作用的存在、持续或可逆性。与对照组相比，联合或不联合佐剂给予TT-6-AmHap在治疗组中诱导了高抗体特异性IgG。该研究发现TT-6-AmHap对死亡率、体格检查、皮肤Draize观察、体重、体重变化、食物消耗、眼科检查、临床病理学（血液学、凝血、临床化学和尿液分析）、大体病理学或器官重量均无相关影响。在本研究条件下，这些结果表明，联合或不联合佐剂的TT-6-AmHap疫苗耐受性良好、具有免疫原性，并且在雄性和雌性兔子中其作用均不被认为是有害的。
