Modified Viral Particles with Immunogenic Properties and Reduced Lipid Content Useful for Treating and Preventing Infectious Diseases

Abstract

The present invention relates to a method for reducing the occurrence and severity of infectious diseases, especially infectious diseases in which lipid-containing infectious viral organisms are found in biological fluids, such as blood. The present invention employs solvents useful for extracting lipids from the lipid-containing infectious viral organism thereby creating modified viral particles with reduced infectivity and enhanced antigenicity. The present invention provides vaccine compositions, comprising these modified viral particles with reduced infectivity and enhanced antigenicity, optionally combined with a pharmaceutically acceptable carrier or an immunostimulant. The vaccine composition is administered to a patient to provide protection against the lipid-containing infectious viral organism. The vaccine compositions of the present invention include combination vaccines of modified viral particles obtained from one or more strains of a virus and / or one or more types of virus.

Description

RELATED APPLICATIONS[0001]This application is a continuation-in-part of U.S. non-provisional patent application Ser. No. 10 / 601,656 filed Jun. 20, 2003, which is a continuation-in-part of U.S. non-provisional patent application Ser. No. 10 / 311,679 filed Dec. 18, 2002, which is a U.S. national phase from PCT patent application number PCT / IB11 / 01099 filed Jun. 21, 2001, which claims the benefit of Australian patent application PQ8469 filed Jun. 29, 2000 and PCT patent application number PCT / AU00 / 01603 filed Dec. 28, 2000. U.S. non-provisional patent application Ser. No. 10 / 311,679 claims the benefit of U.S. provisional patent application Ser. No. 60 / 390,066 filed Jun. 20, 2002. The present application also claims the benefit of U.S. provisional patent application Ser. No. 60 / 491,928 filed Aug. 1, 2003, 60 / 533,542 filed Dec. 31, 2003, and 60 / 542,947 filed Feb. 9, 2004.FIELD OF THE INVENTION[0002]The present invention relates to a delipidation method employing a solvent system useful fo...

AI Technical Summary

Benefits of technology

The present invention provides a simple, effective, and efficient method for treating and preventing viral infections by removing lipid from the lipid envelope of a virus and creating a non-synthetic, host-derived or non-host-derived modified viral particle that has at least one antigen exposed. This method does not denature or destroy the virus, and it induces an immune response in the patient, providing protection against the virus. The method can be used to create a vaccine by treating a biological fluid containing the virus and reintroducing it into the patient. The invention also provides a modified viral particle and an antigen delivery vehicle for creating a vaccine and a method for creating an antigen delivery vehicle.

Problems solved by technology

Viruses, of varied etiology, affect billions of animals and humans each year and inflict an enormous economic burden on society.

Viruses affect animals and humans causing extreme suffering, morbidity, and mortality.

The immune system is forced to produce the “compromise”, ineffective antibodies which do not destroy the viral particles, allowing them to proliferate and slowly cause severe damage to the body, while destroying host cells.

The high mutation rate of the virus, especially in the case of HIV, is a major difficulty with existing treatments because the various strains become resistant to anti-viral drug therapy.

Furthermore, anti-viral drug therapy treatment may cause the evolution of resistant strains of the virus.

Other drawbacks to drug therapies are the undesirable side effects and patient compliance requirements.

Such individuals require even more aggressive and expensive drug regimens to counteract disease progression, which in turn cause greater side effects and a greater likelihood of multiple drug resistance.

Strict adherence to HAART regimen remains a major hurdle, and lapses in compliance lead to bursts of viral replication, and selection of drug resistant strains.

Additionally, long-term use of HAART is associated with side effects such as lipodystrophies, altered glucose metabolism and elevated cholesterol and triglycerides in plasma.

The current methods of vaccination do have drawbacks, making them less than optimally desirable for immunizing individuals against particular pathogens, especially HIV.

One explanation offered in the prior art is that the antigens of these microorganisms change constantly so the antibodies produced in response to a particular antigen are no longer effective when the antigen mutates.

Although antigenic variation has been addressed via the attempted use of combination drugs or antigens, no prior art vaccine has succeeded in addressing chronic infections such as HIV.

Viral inactivation does present problems since inactivation of a virus does not provide a protective immune response against viral infection.

In addition, it is largely geared towards denaturing viral proteins, thereby destroying the structure of the viral particle.

In sum, prior art methods have largely focused on destroying, yet not suitably modifying, viral particles to produce an immune response.

In addition to dissolving the lipid envelope of the virus, the high organic solvent concentrations cause cell death and damage to the antigens.

Essentially, this method results in a “chemical kill” of the cell.

Although treating the virus with glutaraldehyde effectively delipidates the virus, it also destroys the core.

Destruction of the core is not desirable for producing a modified viral particle useful for inducing an immune response in a recipient.

Chloroform, however, denatures many plasma proteins and is not suitable for use with biological fluids, which will be reintroduced into the animal or human.

These functions are essential to life and thus damage to these proteins may have an adverse effect on a patient's health, possibly leading to death.

Many of these methods, especially those involving detergents, require tedious procedures to ensure removal of the detergent before reintroduction of the treated plasma sample into the animal or human.

Further, many of the methods described in the prior art involve extensive exposure to elevated temperature in order to kill free virus and infected cells.

Elevated temperatures have deleterious effects on the proteins contained in biological fluids, such as plasma.

Attenuated vaccines (less infective and not inactivated), however, pose several problems.

First, it is difficult to ascertain when the attenuated vaccine is no longer pathogenic.

The risk of viral infection from the vaccine is too great to properly test for effective attenuation.

In addition, attenuated vaccines carry the risk of reverting into a virulent form of the pathogen.

Images