which contains a cytosine, guanine dinucleotide sequence and stimulates (for example, has a mitogenic effect) vertebrate immune cells
Inventors
KLINMAN, DENNIS M. • Verthelyi, Daniela
Assignees
DEPARTMENT OF HEALTH AND HUMAN SERVICES GOVERNMENT OF United States, THE, Secretary of • US Department of Health and Human Services
Publication Number
US-8263091-B2
Publication Date
2012-09-11
Expiration Date
2023-09-17
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Abstract
A method is disclosed herein for increasing an immune response to an opportunistic infection in an immunocompromised subject. In one embodiment, the subject is infected with a lentivirus. The method includes increasing an immune response to a pathogen using D oligodeoxynucleotides including a CpG motif.
Core Innovation
The invention provides methods for increasing an immune response to opportunistic infections in immunocompromised subjects. Specifically, the methods involve administering therapeutically effective amounts of immunostimulatory oligodeoxynucleotides (ODNs) that include an unmethylated cytosine-guanine dinucleotide (CpG) motif. These ODNs can be of the D type or the K type and are used to enhance immune responses to pathogens, especially in subjects infected with lentiviruses such as human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV).
The problem addressed arises from immunocompromised individuals, such as those with HIV/AIDS, who exhibit a weakened immune system incapable of effectively responding to infections or vaccines. These subjects are susceptible to a range of opportunistic infections caused by viruses, bacteria, fungi, protozoa, and neoplasms. Current treatments are insufficient to enhance immune responses in these individuals. Thus, there is a need for agents that can act as immunoprotective agents to stimulate the immune system in these compromised subjects.
Claims Coverage
The patent discloses two main inventive features based on independent claims involving immunostimulatory oligodeoxynucleotides for enhancing immune responses in immunocompromised subjects.
Method of increasing immune response to Leishmania infection in immunocompromised subjects infected with HIV or SIV
A method involving selecting an immunocompromised subject infected with a secondary Leishmania infection and immunocompromised due to HIV or SIV infection, administering a therapeutically effective amount of a combination of three specific oligodeoxynucleotides with sequences set forth as SEQ ID NOs: 176, 177, and 178, and assessing the immune response to increase the response to Leishmania infection.
Use of immunostimulatory oligodeoxynucleotides without an antigenic polypeptide epitope to enhance immune response in HIV-infected immunocompromised subjects
A method comprising administering a therapeutically effective amount of the three specific oligodeoxynucleotides comprising SEQ ID NOs: 176, 177, and 178 to an immunocompromised subject infected with human immunodeficiency virus without administering an antigenic epitope of a polypeptide from the pathogen, thereby increasing the immune response to the opportunistic infection (Leishmania).
The independent claims focus on methods of enhancing immune responses to opportunistic Leishmania infections in immunocompromised subjects infected with HIV or SIV by administering defined immunostimulatory oligodeoxynucleotides, either alone or without co-administration of antigenic polypeptides, and optionally in combination with anti-retroviral therapies.
Stated Advantages
The methods provide immunoprotective effects in immunocompromised individuals, enhancing their immune response to opportunistic infections.
Administration of D type CpG oligodeoxynucleotides reduces lesion size upon Leishmania infection in non-human primates, demonstrating protective activity in vivo.
Both D and K type CpG ODNs serve as effective adjuvants to vaccines, boosting antibody responses even in immunocompromised subjects.
The approaches enable immune activation in HIV or SIV infected subjects who otherwise have impaired immune responses, including improvement in dendritic cell maturation and cytokine production.
Documented Applications
Increasing immune response to opportunistic infections, including bacterial, viral, fungal, protozoal infections, and neoplasms in immunocompromised subjects such as those infected with HIV or SIV.
Use in immunocompromised subjects infected with lentiviruses to improve responses to infections with Leishmania and other opportunistic pathogens.
Adjunct therapy combined with highly active anti-retroviral therapy (HAART) including drugs such as AZT for HIV treatment.
Use as vaccine adjuvants to improve immunogenicity of vaccines like hepatitis B vaccine in both healthy and SIV infected rhesus macaques.
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