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

Abstract

Tobacco smoking is the cause of 20% of Canadian deaths per year. Nicotine vaccines present a promising alternative to traditional smoking cessation products, but to date, no vaccine has been able to move through all phases of clinical trials. We have previously demonstrated that the AFPL1-conjugate nicotine vaccine does not induce systemic or immunotoxicity in a mouse model and that a heterologous vaccination approach is more advantageous than the homologous routes to inducing mucosal and systemic anti-nicotine antibodies. The purpose of this study was to confirm the safety profile of the vaccine in a repeat-dose toxicity study. The heterologous vaccination strategy was again used, and Sprague Dawley rats were administered a dose five times greater than in our previous studies. Physiological conditions, food and water consumption, body temperature, injection site inflammation, relative weights of organs, histopathology, and blood chemistry and hematology were evaluated during the course of the vaccination period to determine the safety of the vaccine. The AFPL1-conjugate nicotine vaccine did not induce clinically relevant changes or induce symptoms that would be associated with toxicity, making it a promising candidate for future investigations.

Repeat-dose and local tolerance toxicity of SARS-CoV-2 FINLAY-FR-02 vaccine candidate in Sprague Dawley rats

“…1 ), with no statistical significant differences among the three experimental groups. The growth curves were similar to other published curves for this animal model ( Oliva-Hernández et al, 2018 , Oliva et al, 2019 , Oliva-Hernández et al, 2019 ). This is the first evidence of product safety.…”

“…These parameters were measured as reported ( Oliva-Hernández et al, 2018 , Oliva et al, 2019 , Fraleigh et al, 2019 ), on day 0 (before and after injection), at 4, 8, 24, 48 and 72 h after the first dose and 72 h after last dose (in total, during 120 h). Body and injection site temperatures were measured with a laser clinical thermometer (Equate, non-contact forehead thermometer, model #10857, Mississauga, ON, Canada) on the thorax previously depilated and on the internal part of the legs.…”

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

“…As previously reported, the vaccine formulation design is focused on mucosal immunity. The core of this conjugate nicotine vaccine platform is composed of a bacterial-derived adjuvant (BDA) from either N. meningitides or V. cholerae and both have been used as part of effective human vaccines [11,12,[19][20][21][22]. The mucosal multiadjuvanted BDA is able to stimulate immune responses by activating antigen-presenting cells leading to effective adaptive immune responses [20], reviewed in [22].…”

“…No significant decreases in weights were recorded throughout the vaccination protocol with both the controls and the vaccinated groups ( Figure 1C,D) steadily gaining weight on par with Charles River's growth curves for the BALB/c strain [25]. We had previously demonstrated a more robust safety profile [11,19] and used the parameters mentioned to ensure the health of the mice throughout the protocol so that they were healthy for the nicotine challenge.…”

“…The bacterial-derived adjuvant (BDA)-conjugate nicotine vaccine was prepared in house (HSNRI, Sudbury, ON, Canada) as previously reported [11,12,19,20]. Mice were vaccinated under light anesthesia using isoflurane once every 3 weeks using either the homologous (3 IM) or heterologous strategy (1 IM simultaneously with an IN and 2 subsequent IN) with either PBS or the nicotine vaccine as previously described [12].…”