Novel adjuvant based on a proteoliposome‐derived cochleate structure containing native lipopolysaccharide as a pathogen‐associated molecular pattern

Abstract

Summary Proteoliposomes (PL) from Neisseria meningitidis B have been widely used as a core antigen for antimeningococcal vaccination. PL contain major outer membrane proteins, LPS and phospholipids, and they induce a strong Th1 immune response, but they have low stability in solution. Attending to the need for new vaccine adjuvants, we developed a highly stable cochleate structure (CS) from PL using a technology that allows easy incorporation of new antigens. We explored the ability of PLCS to activate the immune system and its possible application as an adjuvant for parenteral and mucosal routes. Our results showed that PLCS were able to upregulate the expression of MHC class II and costimulatory molecules on human dendritic cells, as well as being able to stimulate the production of soluble mediators of a Th1 response, such as IL-12 and nitric oxide. High levels of anti-PL IgG were detected in serum after i.m. or mucosal (oral and nasal) administration, but also anti-PL secretory IgA was produced in saliva following nasal delivery. The immune response polarization to a Th1 pattern was confirmed by the induction of IgG2a antibodies, positive delayed type hypersensitivity reactions, and IFN-γ production by splenocytes from immunized mice. The adjuvant potential was explored using PLCS containing ovalbumin (Ova). PLCS-Ova was able to elicit a substantial increase in anti-Ova IgG compared with Ova alone. In addition, a significant reduction in lesion size was observed in mice immunized with Leishmania major antigens in PLCS after challenge with virulent protozoa, suggesting at least partial modulation of the Th2 environment induced by this parasite. In conclusion, our results support the use of PLCS as a potent Th1 adjuvant for parenteral and mucosal vaccines.

Recent Advances in Drug Delivery Systems

“…Furthermore, cochleates are stable particles (more than other lipidic structures) derived from liposomes composed mainly of charged phosphatidylserine in the presence of divalent counter ion such as Ca 2+ which forms a continuous large lipid bilayer sheet with no internal aqueous space [35,42,43]. Cochleate delivery has shown potential use for amphotericin B, factor VIII delivery, proteins, peptides and DNA [43,44]. Finally, there are cubosomes.…”

“…PLGA blended with different stabilizers [76] and cochleates [44] demonstrated good in vivo vaccination, capable of overcoming nasal cell membranes. As well, genetic vaccination has the potential to treat and prevent several diseases for which conventional vaccines are ineffective and limited [77].…”

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

“…immunization of mice with proteoliposome cochleate vaccine enhances antigen-specific immunoglobulin (Ig) A response in saliva, it fails to promote serum IgG responses. 34 Also, liposomes/cochleates made from unsaturated ester lipids need to be protected from exposure to air during preparation/storage to avoid stability and efficacy issues arising from lipid oxidation. 35,36 In spite of promising animal model studies, currently there is no lipid-based mucosal adjuvant/delivery system product in the marketplace for mucosal vaccination of humans.…”

“…In addition, the protocols developed for preparing liposomes are generally applicable for making archaeosome formulations. Since liposomes 59 and proteoliposome cochleates 34 have been produced at industrial scales, similar processes should be amenable for large-scale production of archaeosome/AMVAD formulations. With the promising efficacy, safety profile, stability and scalability for production, the AMVAD system represents a promising technology for mucosal vaccines development.…”

OMV-based vaccine formulations against Shiga toxin producingEscherichia colistrains are both protective in mice and immunogenic in calves

“…34 These properties, combined with low-cost production processes at the industrial level, make them promising vaccine candidates. 36 …”