The VesiVax system: a method for rapid vaccine development

Abstract

The VesiVax system is based upon the concept that highly potent vaccines can be designed by engineering proteins that are capable of stably inserting themselves into liposomes. Such a nanoscale liposomal particle can then serve as an immunogen for vaccine development. The VesiVax vaccine technology platform is designed to make it relatively easy to engineer and produce new vaccines quickly. Vaccines based on the VesiVax system have been designed against the influenza virus and herpes simplex type 2 virus, the causative agents of the "flu" and genital herpes, respectively. Both vaccines have been tested in animal models and have demonstrated significant protective efficacy from challenge with lethal doses of virus. Assays of the immunological parameters suggest that both T and B cell responses can be elicited by VesiVax vaccines. The safety profile of the VesiVax vaccines is expected to be much better than that of vaccines prepared by conventional techniques. Taken together, the inherent flexibility of the VesiVax platform is expected to facilitate the rapid development of new vaccines which are effective at stimulating protective immune responses.

Liposomal gD ectodomain (gD1–306) vaccine protects against HSV2 genital or rectal infection of female and male mice

“…By using the gD 1-306 ectodomain, the host APCs (antigen-presenting cells) can process the entire antigen and present different peptides to the various T cell populations via either MHC class I or class II [36]. The larger size of the gD 1-306 ectodomain antigen in comparison to the much smaller gD 264-285 epitope segment may also contribute to the enhanced protection that we observed because it would be a larger target for the immune system [23] and this might have enhanced the phagocytic uptake of L-gD 1-306 -HD/MPL compared to L-gD 264 - 285 -HD/MPL.…”

“…In previous studies [23], we observed significant protective effects in female mice challenged intravaginally with HSV2 following immunization with vaccines consisting of single epitopes derived from the HSV2 gD envelope protein and presented to the immune system by a highly immunogenic liposomal delivery vehicle. Within the gD envelope protein, a number of continuous small epitopes have been identified that are of potential vaccine interest because they are postulated to be located on protein surfaces, especially in regions where highly hydrophilic residues are present in beta turns [24], [25], [26], [27], and they mediate antibody-dependent cellular cytotoxicity [28].…”

Cyanuric chloride as the basis for compositionally diverse lipids

“…186003034) using a water, acetonitrile and methanol mixture as described in the gures below and detected at 205 and 254 nm. 1 H and 13 C NMR spectra were recorded in deuterated chloroform using a Varian 400 MHz or Varian 500 MHz spectrometer equipped with a 5 mm OneProbe (Cambridge Isotope Laboratories, Inc.; Tewksbury, MA). HR-MS was performed on an Agilent 6230B TOF LC/MS instrument in positive ion by direct injection of the compounds.…”

“…11 Incorporating adjuvants and antigens in the same formulation has also improved antigen exposure to immune cells and enhanced the efficacy of liposomal vaccines. 12,13 However, the need for synthetic lipids that serve as a platform to generate structure immunogenicity relationships are critical to advance the eld of liposomal vaccine design.…”

All‐trans retinoic acid potentiates the antibody response in mice to a lipopeptide antigen adjuvanted with liposomal lipid A

“…Liposomes composed of 15:2:3 dimyristoylphosphatidylcholine: dimyristoylphosphatidylglycerol:cholesterol with MPL, RA and lipopeptide, as indicated, were formed by hydration of dried lipid films in sterile PBS followed by extrusion through 400 nm polycarbonate membranes. 22 Vesicle size was characterized by dynamic light scattering and z-potential was determined by electrophoretic mobility (Zetasizer 3000, Malvern, New Bedford, MA, USA). Liposome association of N-MPR-DSG and RA was determined by absorbance following sedimentation by ultracentrifugation as described.…”