Method and system for inactivating virus infectivity for producing live-attenuated vaccines
Inventors
Wu, Yuntao • FU, Yajing • DABBAGH, Deemah • Zhou, Zheng
Assignees
Publication Number
US-11116833-B2
Publication Date
2021-09-14
Expiration Date
2039-02-08
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Embodiments relate to 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 a HIV vaccine comprising live attenuated, inactivated, or non-infectious HIV particles. Embodiments relate to systems 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 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 describes a method of preparing live-attenuated, inactivated, or non-infectious HIV vaccines by expressing or overexpressing P-selectin glycoprotein ligand-1 (PSGL-1) in HIV producing cells. This approach entails introducing PSGL-1 (or a PSGL-1 mutant) into HIV producing cells, leading to the production and release of HIV virion particles that are rendered non-infectious, inactivated, or attenuated. Following their isolation, these defective HIV particles are formulated as an HIV vaccine.
The core problem addressed is the lack of effective methods for preparing live attenuated or inactivated HIV vaccines, as current chemical and biological approaches often alter viral immunogenicity or require gene mutations with unknown safety profiles. The existing chemical inactivation methods destroy viral structures and can lead to altered immunogenicity or chemical contamination, while biological methods depend on specific mutations that may not be known or safe for viruses like HIV.
This invention bypasses both chemical treatments and the need for specific gene mutations by using PSGL-1 expression or overexpression in HIV producing cells to directly inactivate or attenuate virus infectivity. Virus particles produced in these conditions incorporate PSGL-1, which impairs their ability to attach and enter target cells. As a result, these virus particles can be isolated and used as components of live-attenuated, inactivated, or non-infectious HIV vaccines without relying on conventional inactivation protocols.
Claims Coverage
There is one independent claim in this patent, which is broadly directed at a composition involving a modified HIV particle.
HIV particle with deleted Vpu and incorporated PSGL-1 or PSGL-1 mutant
The composition comprises a human immunodeficiency virus (HIV) particle with a deleted Vpu gene. The particle has P-selectin glycoprotein ligand-1 (PSGL-1) or a PSGL-1 mutant directly incorporated into the viral particle. The HIV particle in the composition is specified as a non-infectious HIV particle, an attenuated HIV particle, or an inactivated HIV particle.
The inventive feature centers on generating non-infectious, attenuated, or inactivated HIV particles—lacking Vpu and carrying PSGL-1 or a PSGL-1 mutant—intended for compositions such as vaccines.
Stated Advantages
The method allows the production of non-infectious, inactivated, or attenuated HIV particles without the use of chemicals that alter the structure of the virus or host cells.
Vaccines produced by this approach preserve the native structure of the HIV particle, which may result in improved immunogenicity compared to chemically treated virus particles.
The process avoids contamination with chemical impurities, overcoming a major drawback of chemical inactivation methods.
The incorporation of PSGL-1 effectively renders the virus particles non-infectious, addressing the challenge of developing safe, live-attenuated or inactivated HIV vaccines when genetic mutations for safe attenuation are not known.
Documented Applications
Preparation of HIV vaccines comprising live attenuated, inactivated, or non-infectious HIV particles produced by expressing or overexpressing PSGL-1 in HIV producing cells.
Administration of such vaccines to subjects to treat or prevent disease states resulting from HIV infection.
Interested in licensing this patent?