Method and system for inactivating virus infectivity for producing live-attenuated vaccines

Inventors

Wu, Yuntao • FU, Yajing • DABBAGH, Deemah • Zhou, Zheng

Assignees

George Mason University

Abstract

Embodiments relate to methods comprising expressing or overexpressing P-selectin glycoprotein ligand-1 (PSGL-1) in human immunodeficiency virus (HIV) producing cells; isolating HIV particles from the HIV producing cells; and preparing the isolated HIV particles as a HIV vaccine. Embodiments relate to systems comprising a HIV vaccine comprising live attenuated, inactivated, or non-infectious HIV particles. Embodiments relate to systems capable of performing a method comprising administering a vaccine comprising live attenuated, inactivated, or non-infectious HIV particles to a subject in need of the vaccine; and treating or preventing one or more disease states in the subject resulting from HIV infection. Embodiments relate to methods comprising expressing or overexpressing PSGL-1 in virus producing cells; and inhibiting viral infection; or inhibiting viral spreading; or inactivating viruses and virus producing cells; or producing non-infectious virion particles; or allowing the virus producing cells to produce non-infectious virions, isolating the virions, and preparing non-infectious virions, the virions being HIV particles.

Core Innovation

The invention provides methods for preparing vaccines against viruses, particularly HIV, by expressing or overexpressing P-selectin glycoprotein ligand-1 (PSGL-1) in virus producing cells. This process results in the production of HIV particles that are non-infectious, attenuated, or inactivated. The HIV particles are isolated from these cells and prepared for use as a vaccine. Notably, chemical agents that alter the structure of virus producing cells are not required, differentiating this method from prior chemical inactivation processes.

The patent addresses the problem that existing methods of creating live attenuated or inactivated viral vaccines for viruses such as HIV are inadequate. Chemical inactivation methods may destroy viral structure, reducing immunogenicity, and can leave harmful chemical residues. Biological attenuation methods require knowledge of specific gene mutations, which for some viruses like HIV is lacking, and may still result in residual infectivity. No existing reliable biological method is described for attenuation or inactivation of HIV virions for vaccine preparation.

By expressing or overexpressing PSGL-1 in HIV-producing cells, the method described produces virion particles that lose their capacity to infect target cells, effectively inactivating viral infectivity through a cellular mechanism. This approach enables the generation of live attenuated, inactivated, or non-infectious HIV particles that can be used in vaccines, with the PSGL-1 protein acting at the level of the virus producer cell to restrict infectivity. The method also encompasses the administration of such vaccines to subjects to treat or prevent disease states resulting from HIV infection.

Claims Coverage

The patent includes three independent claims, each directed to inventive methods for producing non-infectious, attenuated, or inactivated HIV or virus particles through the expression of PSGL-1 or its mutant in virus producing cells.

These inventive features collectively cover in vitro methods for generating non-infectious, attenuated, or inactivated HIV or virus particles by overexpressing PSGL-1 or its mutant in producing cells using recombinant technologies, for vaccine or immunization purposes.

Stated Advantages

Documented Applications