Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity

Abstract

Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin-OVA) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-PamC), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

Materials for Immunotherapy

“…In contrast to micelles made from synthetic polymers, PAMs can also easily display antigens along their corona, increasing their usefulness for applications in antigen‐presentation. Not only so, PAMs permit the incorporation of antigens at various locations throughout the micelle, which has been shown to dictate vaccine potency . PAMs, and more broadly peptide‐based micelles, represent the largest class of micelles used in immunotherapy; thus this section is devoted to the seminal advances within this class of materials.…”

Group B meningococcal outer membrane protein vaccine promote potent anti-viral effect

“…The combination of nucleic acid priming protein-enhanced immunoassay has made progress in the study of vaccines such as schistosomiasis, Japanese encephalitis, brucellosis, AIDS, tuberculosis 1-3 , malaria, etc., and its immune response is superior to a single nucleic acid vaccine or Protein vaccine [16 19]. Whether the N. meningitidis NMB0315 vaccine adopts the nucleic acid priming protein-enhanced combination immunization method is superior to the protein vaccine or nucleic acid vaccine alone [4][5][6][7][8][9][10][11][12] , has not been reported yet, and deserves further research and exploration.…”

“…The bacteria can invade the brain and spinal cord of humans, causing suppurative infections, which can cause permanent damage to the brain and nervous system [1 4]. Nm's Capsular polysaccharide (CPS), Outer membrane protein (OMP) and lipooligosaccharides are important virulence factors [5]. At present, the C group, A+C group and the mixed vaccines of group A, C, W and Y developed by capsular polysaccharide prion protein carrier effectively control meningococcal diseases caused by group A, C, W and Y.…”

Immunogenicity assessment of PRRS polylactic acid glycolic acid DNA vaccine

“…7, when immunized with the same dose of DNA, the neutralizing antibody of PLGA/CTAB-DNA microparticle immunization group was higher than that of naked DNA vaccine immunization group 8 weeks after the first dose (P<0. 05), and at low dose [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] .…”

“…Polylactic acid-glycolic acid (PLGA) is a biodegradable polymer with good biocompatibility and is widely used in pharmaceuticals, especially as a macromolecular drug delivery carrier [4][5]. The positively charged PLGA/CTAB microparticles prepared by PLGA can effectively adsorb and protect DNA, and the slow release can improve the half-life and immune effect of the adsorbed DNA vaccine in vivo [6]. It has been confirmed in studies of human immunodeficiency virus (HIV) and foot-and-mouth disease virus (FMDV) that PLGA/CTAB microparticles can significantly enhance the immune response induced by DNA vaccines [7][8].…”