Methods and compositions for adaptive immune modulation

Inventors

Dickey, Burton F. • Tuvim, Michael J. • Evans, Scott E. • Hook, Magnus • Huston, David P. • MARTINEZ-MOCZYGEMBA, Margarita • Scott, Brenton

Assignees

Pulmotect Inc • Texas A&M University System • University of Texas System

Abstract

Embodiments are directed to methods and compositions for modulating an immune response. In certain aspects the immune response is a type I hypersensitivity response. In particular aspects the subject has allergic asthma or allergic rhinitis. Using a conventional experimental asthma mouse model (BALB/c), the inventors demonstrate that aerosol administration of TLR agonists, in particular a combination of TLR2/6 and TLR9 agonist (e.g., TLR9 oligonucleotide agonist/PAM2CSK4) along with an antigen (e.g., ovalbumin (OVA)) suppresses the immune response as exemplified by the production of antigen-specific IgE and decreases the number of airway eosinophils in bronchoalveolar lavage fluid (BAL) in response to intraperitoneal (IP) immunization with an antigen mixed with alum.

Core Innovation

Discloses adaptive immune modulation for type I hypersensitivity by aerosol co-administration of TLR2/6 and TLR9 agonists together with an antigen. The approach targets allergen-induced asthma and allergic inflammation by combining PAM2CSK4 with TLR9 CpG oligonucleotides, including ODNM362. The combined use of these TLR agonists is used to attenuate type I hypersensitivity in a subject susceptible to allergen induced asthma.

In a BALB/c OVA/alum sensitization and challenge model, aerosol OVA-O/P suppresses antigen-specific and total IgE and reduces airway eosinophils in bronchoalveolar lavage. The treatment increases serum IgG2a as a Th1 marker while shifting away from Th2-type allergic inflammation. The described immunomodulatory effect is supported by bronchoalveolar lavage readouts including antigen-specific and total IgE and airway eosinophils.

The disclosure further includes additional optimization of sensitization/challenge timing and dose scheduling in support of the immunomodulatory effect. It also describes embodiments involving aerosol or nebulized administration and delivery devices for administering the combined composition. The disclosed formulations are described as sterile and essentially free of pathogenic microbes and may include a glycerol excipient.

Claims Coverage

The partial claims identify three independent claims. Across these, the core coverage centers on attenuating type I hypersensitivity using a composition that combines PAM2CSK4 with ODNM362, either as a method of administration to a susceptible subject or as a pharmaceutically acceptable composition including an asthma-inducing allergen, optionally with further formulation restrictions.

The independent claims collectively cover administering PAM2CSK4 plus ODNM362 to attenuate type I hypersensitivity in allergen-induced asthma, using PAM2CSK4 and ODNM362 as the specified TLR agonists in a composition together with an allergen, and a pharmaceutically acceptable composition comprising PAM2CSK4, ODNM362, and an asthma-inducing allergen.

Stated Advantages

Documented Applications