enhancing the immunogenicity of a vaccine against Bacillus anthracis by administering an oligodeoxynucleotide with a vaccine against Bacillus anthracis; Anthrax Vaccine Adsorbed (AVA) vaccine

Inventors

KLINMAN, DENNIS M.Ivins, BruceVerthelyi, Daniela

Assignees

DEPARTMENT OF HEALTH AND HUMAN SERVICES GOVERNMENT OF United States, Secretary ofUS Department of Health and Human Services

Publication Number

US-7758876-B2

Publication Date

2010-07-20

Expiration Date

2023-10-31

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Abstract

The present disclosure relates to a method of preventing or treating an infection caused by a bioterrorism agent, specifically to a method of increasing an immune response to a bioterrorism agent using an oligodeoxynucleotide including a CpG motif, and a method of enhancing the immunogenicity of a vaccine against a bioterrorism agent using an oligodeoxynucleotide including a CpG motif.

Core Innovation

The invention relates to methods of increasing the immune response to bioterrorism agents by administering immunostimulatory oligodeoxynucleotides (ODNs) that include unmethylated CpG motifs, specifically D and K type ODNs. These oligodeoxynucleotides can be administered alone, in combination with additional anti-infective agents, or alongside vaccines against bioterrorism agents to enhance their immunogenicity.

The background highlights the challenge posed by bioterrorism agents such as Bacillus anthracis, which require robust immune responses for protection. The licensed Anthrax Vaccine Adsorbed (AVA) vaccine requires multiple doses over an extended period and is associated with undesirable side effects in some recipients. There is a need for agents that can prevent or treat infections caused by bioterrorism agents or increase the immunogenicity of vaccines to reduce dosing schedules and improve protective efficacy.

The summary describes methods of treating or preventing infections in subjects exposed or at risk of exposure to bioterrorism agents by administering therapeutically effective amounts of immunostimulatory D or K oligodeoxynucleotides. These methods include administering the ODNs alone, with anti-infective agents, or co-administered with vaccines against bioterrorism agents, including antigens from Bacillus anthracis like protective antigen (PA). The co-administration enhances the immune response to these vaccines, potentially improving protection.

Claims Coverage

The patent includes one independent claim focusing on a method for enhancing the immunogenicity of vaccines against Bacillus anthracis using a specific oligodeoxynucleotide sequence.

Use of specific oligodeoxynucleotide sequence to enhance vaccine immunogenicity

Administering to a subject a therapeutically effective amount of an oligodeoxynucleotide consisting of the nucleic acid sequence set forth as SEQ ID NO: 200 in combination with a vaccine against Bacillus anthracis to enhance the vaccine's immunogenicity.

Enhancement of immunogenicity of Anthrax Vaccine Adsorbed (AVA) vaccine by co-administration

Administering a therapeutically effective amount of the oligodeoxynucleotide SEQ ID NO: 200 together with Anthrax Vaccine Adsorbed (AVA) vaccine to enhance immunogenicity, including increasing IgG or IgM titers and improving survival upon subsequent anthrax exposure.

The claims cover methods of enhancing the immunogenicity of Bacillus anthracis vaccines, particularly AVA vaccine, by administering a therapeutic amount of a specific CpG oligodeoxynucleotide (SEQ ID NO: 200) either before, concurrently, or after vaccination, thereby improving antibody responses and protection against anthrax.

Stated Advantages

CpG ODNs significantly increase the magnitude and duration of the antibody response to Bacillus anthracis vaccines.

Co-administration of CpG ODN with vaccines reduces the number of doses required to achieve protective immunity.

CpG ODN improve the quality of antibody responses by increasing avidity and enhancing functional neutralization capacity.

The immunostimulatory ODNs can provide a window of protection and improve survival times following bioterrorism agent exposure.

Documented Applications

Enhancement of immune response and protective efficacy of vaccines against Bacillus anthracis, including licensed AVA and recombinant protective antigen vaccines.

Treatment and prevention of infections caused by a variety of bioterrorism agents through administration of immunostimulatory CpG oligodeoxynucleotides alone or with anti-infective agents.

Use of CpG ODNs as adjuvants to enhance efficacy and reduce dosing regimens in vaccines against other bioterrorism agents, such as Ebola virus and tick-borne encephalitis virus.

Formulations involving CpG ODN encapsulated in poly(lactide-co-glycolide) microparticles to improve delivery and immune response against Bacillus anthracis.

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