Molecular Express specializes in the design and engineering of functionalized liposomes for drug delivery and vaccine development. In previous studies, an extensive set of liposome formulations were screened to establish the optimal lipid combination that meets certain physicochemical parameters and provides strong immune responses in animals. These unilamellar vesicles have diameters of approximately 100 nm, are stable (i.e., no aggregation, precipitation or degradation of the components for over a year) in biological buffer solutions, and are commercially scalable. The immunogenic liposome compositions form the basis of a vaccine platform technology called the VesiVax(r) system. The VesiVax(r) system was designed to be easily manipulated, so that target antigens could be displayed from the surface of the immunogenic liposomes for subsequent use in immunization studies. Vaccines based on the VesiVax(r) system can be engineered using two formats: i) target antigens or adjuvant proteins can be engineered to be expressed as a fusion protein with a hydrophobic domain (HD), which facilitates its incorporation into the liposomes or;ii) target antigens or adjuvants in the form of proteins, peptides or carbohydrates can be attached via conjugation to the surface of the liposomes (i.e., conjugatable adjuvant lipid vesicles;CALVs). The flexibility of the VesiVax(r) platform allows both antigens and adjuvants to be formulated together into the liposomes thus maximizing the immune response. In this SBIR AT Phase I proposal, we intend to establish the utility of the VesiVax(r) CALV platform as an effective adjuvant for virus-like particles (VLPs). To demonstrate this concept, we propose to prepare VesiVax(r) CALV formulations containing different Toll-like Receptor (TLR) agonists and then conjugating them to VLPs that have been designed to express HIV antigens (HIV-VLPs) (Specific Aim 1). The VesiVax(r) CALV HIV-VLPs will then be tested in mouse and rabbit models (Specific Aim 2). These studies are potentially of high impact because demonstration that: I) the VesiVax(r) CALVs can adjuvant VLPs would have an immediate impact through increasing sales of the CALV line of research kits;II) the sublingual route of administration stimulates potent immune responses would be another useful application of the VesiVax(r) technology and;III) one or more VesiVax(r) CALV HIV-VLP formulations stimulate potent HIV antibody neutralization activity in the in vitro assays will set the stage for the selection of one or more of these candidates to undergo further testing in non-human primates prior to final selection of a VesiVax(r) CALV HIV-VLP candidate that will be advanced to clinical testing. Such a vaccine will provide the basis for a cost effective HIV immunization strategy that could be implemented on a global scale.
Since its discovery in the early 1980's, the Human Immunodeficiency Virus (HIV), the etiologic agent of the Acquired Immunodeficiency Syndrome (AIDS), has caused the deaths of millions of humans and continues to be a significant health problem throughout the world, especially in third world countries. Although anti-HIV drugs have had a positive impact on reducing the threat of AIDS, the HIV infection rate is still at alarming levels and hence, it is now more apparent than ever that the development of an effective HIV vaccine will be the only cost effective strategy that will bring AIDS under control. While immunization has generally been a successful approach for controlling many infectious diseases, the development of a vaccine that provides broad protective immunity against infection by HIV has proven to be problematic. The application of new immunization techniques to develop affordable, advanced prophylactic HIV vaccines that provide broad protection is now a high priority for the global research community. In this SBIR AT proposal, we intend to establish the utility of the VesiVax(r) CALV platform as an effective adjuvant for virus-like particles (VLPs). To demonstrate this concept, we propose to prepare VesiVax(r) CALV formulations containing different Toll-like Receptor (TLR) agonists and then conjugating them to VLPs that have been designed to express HIV antigens (HIV-VLPs). We will also establish that the VesiVax(r) CALV HIV-VLPs can be administered by the more convenient sublingual route of immunization. Successful demonstration that one or more VesiVax(r) CALV HIV-VLP formulations stimulate potent HIV antibody neutralization activity in the in vitro assays will set the stage for the selection of one or more of these candidates to undergo further testing in non-human primates prior to final selection of a VesiVax(r) CALV HIV-VLP candidate that will be advanced to clinical testing. Such a vaccine will provide the basis for a cost effective HIV immunization strategy that could be implemented on a global scale and hence, would be of great benefit to the public.
| Poteet, Ethan; Lewis, Phoebe; Chen, Changyi et al. (2016) Toll-like receptor 3 adjuvant in combination with virus-like particles elicit a humoral response against HIV. Vaccine 34:5886-5894 |
| Poteet, Ethan; Lewis, Phoebe; Li, Feng et al. (2015) A Novel Prime and Boost Regimen of HIV Virus-Like Particles with TLR4 Adjuvant MPLA Induces Th1 Oriented Immune Responses against HIV. PLoS One 10:e0136862 |
