New Vaccines Require Potent Adjuvants like AFPL1 and AFCo1

Abstract

Neisseria meningitidis B proteoliposome (AFPL1 when used as adjuvant) and its derivative‐Cochleate (AFCo1) contain immunopotentiating and immunomodulating properties and delivery system capacities required for a good adjuvant. Additionally, they contain meningococcal protective antigens and permit packaging of other antigens and pathogen‐associated molecular patterns (PAMP). Consequently, we hypothesized that they would function as good vaccine adjuvants for their own antigens and also for non‐related antigens. AFPL1 is a detergent‐extracted outer membrane vesicle of N. meningitidis B transformed into AFCo1 in calcium environment. Both are produced at Finlay Institute under good manufacture practices (GMP) conditions. We show their exceptional characteristics: combining in the same structure, the potentiator activity, polarizing agents and delivery system capacities; presenting multimeric protein copies; containing multiprotein composition and multi and synergistic PAMP components; acting with incorporated or co‐administrated antigens; inducing type I IFN‐γ and IL‐12 cytokines suggesting the stimulation of human plasmocytoid precursor and conventional dendritic cells, respectively, inducing a preferential Th1 immune response with TCD4+, TCD8+, cross‐presentation and cytotoxic T‐lymphocyte (CTL) in vivo responses; and functioning by parenteral and mucosal routes. AFPL1–AFCo1 protective protein constitutions permit per se their function as a vaccine. In addition to Phase IV Men BC vaccine, AFPL1 has ended the preclinical stage in an allergy vaccine and is concluding the preclinical stage of a nasal meningococcal vaccine. In conclusion, AFPL1 and AFCo1 induced signal 1, 2 and 3 polarizing to a Th1 (including CTL) response when they acted directly as vaccines or were used as adjuvants with incorporated or co‐administered antigens by parenteral or mucosal routes. Both are very promising adjuvants.

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

“…Previously, AFPL1 has been shown to be efficient at upregulating co-stimulatory molecules [25, 26, 27], proinflammatory cytokines and other cytokines involved in adaptive immune responses [27]. AFPL1 activation of TLR4 on antigen presenting cells (APCs) is similar to lipopolysaccharide (LPS), leading to a predominantly Th1 response [27, 28]. AFPL1 has been extensively studied and while it is a Th1 adjuvant, it can induce various different IgG isotypes including IgG2a and IgG1 which are associated with Th1 and Th2 responses respectively [29, 30].…”

Recent advances in the development of novel mucosal adjuvants and antigen delivery systems

“…15,18,[20][21][22][23][24] For some of these adjuvants, issues of actual or perceived toxicity, stability, complexity and scalability of preparation as well as efficacy and duration of induced immune responses remain unresolved. 6,11,13,25,26 For instance, ISCOMATRIX TM (colloidal, spherical structures, comprising of saponin such as Quil A, cholesterol and a phospholipid) has potential as a mucosal adjuvant 27,28 but it may not be easily amenable for use with hydrophilic protein antigens, and concerns/perceptions regarding saponin toxicity remain.…”

“…6,11,13,25,26 For instance, ISCOMATRIX TM (colloidal, spherical structures, comprising of saponin such as Quil A, cholesterol and a phospholipid) has potential as a mucosal adjuvant 27,28 but it may not be easily amenable for use with hydrophilic protein antigens, and concerns/perceptions regarding saponin toxicity remain. 29,30 Cochleate vaccines derived by interaction of multivalent cations with ester lipid liposomes 31,32 or with proteoliposomes 24,33 have been investigated for mucosal…”

“…In contrast, antibody responses against component(s) of some other mucosal delivery systems (e.g., proteoliposomes and viral vectors) have been reported, and this could affect vaccine efficacy upon subsequent use of the delivery system. 20,24,[50][51][52][53] The AMVAD system is self-adjuvanting, requiring no additional immunostimulants. In contrast, liposomes require the inclusion of other immunostimulants or targeting molecules (e.g., cholera toxin B, interleukin-2, monophosphoryl lipid A) to bolster their efficacy as mucosal adjuvants.…”

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

“…In addition, proteoliposomes can be transformed into a microparticles (Adjuvant Finlay Cochleate 1, AFCo1), conserved the protective and adjuvants components [5]. AFCo1 is an effective adjuvant in mice by different mucosal routes and with different antigens [5,6]. Nasal immunization of AFCo1 and glycoprotein gD2 from Herpes Simplex Virus (HSV) induces systemic and mucosal (at local and distal sites) immune responses and total protection against HSV challenge [7].…”