Toxicological assessment of the cochleate derived from Neisseria meningitidis proteoliposome in sprague dawley rats

Abstract

Background:The AFCo1 cochleate is a potential novel adjuvant derived from Neisseria meningitidis B proteoliposome.Aim:The aim was to assessing the safety of AFCo1 by single and repeated doses in Sprague Dawley rats.Materials and Methods:Rats were grouped for treatment with AFCo1, placebo formulation or control. The first study was a single intranasal dose of 100 μl and monitoring body weight, water, and food intakes as well as clinical symptoms. Fourteen days later the rats were killed and anatomopathological studies were conducted. In a second study, four similar doses of the test substance were instilled every 5 days. Clinical observations were carried out as for the single dose study and a number of rats from each group were killed 3 and 14 days after the last dose in order to conduct hematological, hemochemical, and anatomopathological studies.Results:No variable showed differences of toxicological relevance; the histological changes found were mild and similarly frequently in the three groups. According to the irritability index calculated form histology of the nasal region, AFCo1 was also classified as nonirritating.Conclusion:AFCo1 is potentially safe for human use by nasal route as evidenced by the absence of local and systemic signs of toxicity in Sprague Dawley rats.

Repeat-Dose Toxicity Study Using the AFPL1-Conjugate Nicotine Vaccine in Male Sprague Dawley Rats

“…AFPL1 is derived from the safe and clinically used VA-MENGOC-BC ® for protection from Neisseria meningitis B and has been used IN [29][30][31] as part of the institute's mucosal vaccine development. The cochleate, AFCo1, derived from AFPL1, has been shown to be devoid of toxicity when administered repeatedly in SD rats [32]. Because this vaccine is preventative and therapeutic for nicotine addition, adverse side effects are not acceptable [27] and safety evaluations need to be performed, despite the adjuvant having already been established as safe in the literature when delivered either IN or IM.…”

Extreme Resilience in Cochleate Nanoparticles

“…1,2,3 Cochleates have been proposed to be used as biocompatible pharmaceutical vehicles for molecules which are difficult to deliver such as amphotericin B to treat systemic mycoses, 2,3,4,5,6 factor VIII for replacement in haemophilia A, 7,8 or antigens for immunization. 9,10,11,12,13,14,15 In certain applications the active agent itself, rather than calcium, serves as the electrostatic glue that holds the membrane sheets together. 16,17,18,19,20,21 The structure of cochleates has previously been analyzed by using freeze fracture, 1,3,12,22 negative staining, 7,23,24 scanning electron 12,21,25 and light microscopies.…”

“…Cochleates are membrane rolls made of dipalmitoylphosphatidylserine and calcium ions and are so named because of their cross-sectional geometry . In a cochleate particle, the spirally curving and stacked lipid layers are stabilized by calcium ions that cross-link the negatively charged lipid headgroups. − Cochleates have been proposed to be used as biocompatible pharmaceutical vehicles for molecules that are difficult to deliver, such as amphotericin B to treat systemic mycoses, − factor VIII for replacement in hemophilia A, , or antigens for immunization. − In certain applications, the active agent itself, rather than calcium, serves as the electrostatic glue that holds the membrane sheets together. − The structure of cochleates has previously been analyzed using freeze fracture, ,,, negative staining, ,, scanning electron microscopy, ,, and light microscopy. ,,, Although a detailed model has emerged about the geometry of cochleates, very little is known about their internal dynamics, mechanical properties, and structure-stabilizing forces. Considering that the cochleate displays a highly ordered structure despite being composed of a fluid membrane, its elasticity and viscosity need to be investigated experimentally.…”