Nasal immunization of mice with AFCo1 or AFPL1 plus capsular polysaccharide Vi from Salmonella typhi induces cellular response and memory B and T cell responses

Romeu, Belkis; Lastre, Miriam; Reyes, Laura M.; González, Elizabeth Rasche; Borrero, Y; Lescaille, Diandra; Pérez, Rocmira; Nuñez, Darzy; Pérez, Óliver

doi:10.1016/j.vaccine.2014.10.037

Cited by 7 publications

(6 citation statements)

References 37 publications

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“…AFPL1 has been previously tested as an adjuvant [39] and has been shown to induce dendritic cell activation, antigen presentation, TNF-α and IL-12(p70) production [27, 28]. LPS is a component of the bacterial outer membrane, a potent danger signal and inducer of innate immune responses.…”

Section: Resultsmentioning

confidence: 99%

“…This balance is desired for protective immunity against bacterial infections; however, for nicotine vaccine development it is critical to have neutralizing antibodies − including IgA and IgG. Previous investigations have demonstrated that the AFPL1 is able to induce a predominantly Th1 response [26, 27, 28, 39]. The ability of the intranasal nicotine vaccine to potentially induce both Th1 and Th2 responses as seen through IgG2a and IgG1 is similar to previous responses induced by AFPL1 when used as a mucosal adjuvant [29, 30].…”

Section: Resultsmentioning

confidence: 99%

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Evaluating the immunogenicity of an intranasal vaccine against nicotine in mice using the Adjuvant Finlay Proteoliposome (AFPL1)

Fraleigh

Boudreau

Bhardwaj

et al. 2016

Heliyon

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Tobacco smoking is recognized as a global pandemic resulting in 6 million deaths per year. Despite a variety of anti-smoking products available to aid with tobacco cessation, the majority of people who attempt to quit smoking relapse within 6 months due to the addictive nature of nicotine. An immunotherapy approach could offer a promising treatment option by inducing a potent selective antibody response against nicotine in order to block its distribution to the brain and its addictive effects in the central nervous system. Our nicotine vaccine candidate was administered intranasally using the Neisseria meningitidis serogroup B Adjuvant Finlay Proteoliposome 1 (AFPL1) as a part of the delivery system. This system was designed to generate a robust immune response by stimulating IL-1β production through Toll-like receptor 4 (TLR4), a potent mechanism for mucosal immunity. The vaccine induced high antibody titers in mice sera in addition to inducing mucosal antibodies. The efficacy of our vaccine was demonstrated using in vivo challenge experiments with radioactive [3H]-nicotine, followed by an analysis of nicotine distribution in the lung, liver, blood and brain. Our results were encouraging as the nicotine concentration in the brain tissue of mice vaccinated with our candidate vaccine was four times lower than in non-vaccinated controls; suggesting that the anti-nicotine antibodies were able to block nicotine from crossing the blood brain barrier. In summary, we have developed a novel nicotine vaccine for the treatment of tobacco addiction by intranasal administration and also demonstrated that the AFPL1 can be used as a potential adjuvant for this vaccine design.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Evaluating the immunogenicity of an intranasal vaccine against nicotine in mice using the Adjuvant Finlay Proteoliposome (AFPL1)

Fraleigh

Boudreau

Bhardwaj

et al. 2016

Heliyon

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“…AFPL1 has been used extensively as part of adjuvant and vaccine development at the Finlay Institute of Vaccine in Cuba and is multi-adjuvanted with the ability to activate Toll-like receptors (TLRs) 2, 4, and 9 (reviewed by [28]). 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].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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“…Other antigens can also promote IgG responses, including PLc from Vibrio cholerae (54) and other bacterially derived antigens (55). Therefore, the presence of bacterial antigens may naturally augment such responses, possibly by adsorbing the Vi antigen.…”

Section: Discussionmentioning

confidence: 99%

Salmonella Typhi Porins OmpC and OmpF Are Potent Adjuvants for T-Dependent and T-Independent Antigens

et al. 2017

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Several microbial components, such as bacterial DNA and flagellin, have been used as experimental vaccine adjuvants because of their inherent capacity to efficiently activate innate immune responses. Likewise, our previous work has shown that the major Salmonella Typhi (S. Typhi) outer membrane proteins OmpC and OmpF (porins) are highly immunogenic protective antigens that efficiently stimulate innate and adaptive immune responses in the absence of exogenous adjuvants. Moreover, S. Typhi porins induce the expression of costimulatory molecules on antigen-presenting cells through toll-like receptor canonical signaling pathways. However, the potential of major S. Typhi porins to be used as vaccine adjuvants remains unknown. Here, we evaluated the adjuvant properties of S. Typhi porins against a range of experimental and clinically relevant antigens. Co-immunization of S. Typhi porins with ovalbumin (OVA), an otherwise poorly immunogenic antigen, enhanced anti-OVA IgG titers, antibody class switching, and affinity maturation. This adjuvant effect was dependent on CD4+ T-cell cooperation and was associated with an increase in IFN-γ, IL-17A, and IL-2 production by OVA-specific CD4+ T cells. Furthermore, co-immunization of S. Typhi porins with an inactivated H1N1 2009 pandemic influenza virus experimental vaccine elicited higher hemagglutinating anti-influenza IgG titers, antibody class switching, and affinity maturation. Unexpectedly, co-administration of S. Typhi porins with purified, unconjugated Vi capsular polysaccharide vaccine (Vi CPS)—a T-independent antigen—induced higher IgG antibody titers and class switching. Together, our results suggest that S. Typhi porins OmpC and OmpF are versatile vaccine adjuvants, which could be used to enhance T-cell immune responses toward a Th1/Th17 profile, while improving antibody responses to otherwise poorly immunogenic T-dependent and T-independent antigens.

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Nasal immunization of mice with AFCo1 or AFPL1 plus capsular polysaccharide Vi from Salmonella typhi induces cellular response and memory B and T cell responses

Cited by 7 publications

References 37 publications

Evaluating the immunogenicity of an intranasal vaccine against nicotine in mice using the Adjuvant Finlay Proteoliposome (AFPL1)

Evaluating the immunogenicity of an intranasal vaccine against nicotine in mice using the Adjuvant Finlay Proteoliposome (AFPL1)

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

Salmonella Typhi Porins OmpC and OmpF Are Potent Adjuvants for T-Dependent and T-Independent Antigens

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