AMVAD adjuvant for mucosal vaccines (L-11561)

Highlights

Many microbial pathogens invade their mammalian hosts through the mucosal surfaces of the respiratory, gastrointestinal and urogenital tracts. The majority of approved vaccines are administered systemically, and fail to elicit effective mucosal immunity. There is thus a demand for safe, effective, non-replicating mucosal adjuvants and vaccines capable of preventing respiratory infections such as tuberculosis, streptococcal pneumonia, and influenza, as well as sexually transmitted infections such as HIV and genital Chlamydia.

NRC has developed a novel archaeal polar lipid mucosal vaccine adjuvant and delivery (AMVAD) platform capable of generating mucosal and systemic immune responses against a wide range of pathogens that infect mucosal surfaces or use them to gain entry to the body.

Technology transfer

  • Commercial exploitation licence
  • R&D agreement for development

Market applications

  • Vaccines against bacterial and viral pathogens affecting the respiratory system, such as tuberculosis, streptococcal pneumonia, and influenza
  • Vaccines against sexually-transmitted infections, such as HIV and genital Chlamydia

How it works

To address concerns relating to the use of live-attenuated and whole-killed pathogen cells in mucosal vaccines, NRC has developed AMVAD, a self-adjuvanting platform capable of stimulating mucosal immunity against a wide range of pathogens. AMVAD vaccines are formulated by adding multivalent cations to a suspension of antigens and archaeosomes (liposomes made from archaeal polar lipids). The interaction with the cations transforms the small, individual spherical archaeosomes into larger spherical structures that aggregate into clumps (“bunch of grapes”). When presented to the mucosal surface, this “bunch of grapes” elicits mucosal and systemic immune responses, whereas the antigen-archaeosomes that have not interacted with cations do not generate mucosal responses.

Figure: Comparison of small, individual, spherical archaeosomes vs. AMVAD's larger spherical structures aggregated into clumps (“bunch of grapes”) as a result of interaction with cations.

individual, spherical archaeosomes

Archaeosomes

AMVAD's larger spherical structures aggregated into clumps (

AMVAD

Figure: Comparison of small, individual, spherical archaeosomes vs. AMVAD's larger spherical structures aggregated into clumps (“bunch of grapes”) as a result of interaction with cations.

Strong, sustained and memory-boostable antigen-specific IgA antibody responses at local (nasal, respiratory) and distal (gastrointestinal, vaginal) sites were elicited in mice, upon intranasal administration of antigens formulated with AMVAD. Robust, antigen-specific systemic antibody (serum IgG1 and IgG2a) and CD8+ cytotoxic T lymphocyte (CTL) responses were also generated. Intranasal administration of experimental vaccines adjuvanted with the AMVAD system have shown protective efficacies in the murine model of respiratory tularemia using Francisella tularensis live vaccine strain (LVS), and in the genital Chlamydia infection model using Chlamydia muridarum.

Benefits

  • Mucosal (e.g. nasal) or systemic (e.g. subcutaneous) vaccine administration
  • Self-adjuvanting delivery platform
  • Strong, sustained mucosal and systemic immune responses (humoral, CTL)
  • Memory-boostable immune responses
  • Low antigen/adjuvant dose
  • Good preclinical safety profile (no toxicity or anti-lipid antibodies)
  • Excellent stability, significant formulary/storage advantages: < 5% antigen release in 12 months at 5°C
  • Proof-of-concept in murine models of respiratory tularemia and genital Chlamydia

Patents

  • NRC file 11561: Patents granted in Europe, pending in the United States, Canada and India.

Contact

April Luong, Client Relationship Leader
Telephone: 514-496-2745
Email: April.Luong@cnrc-nrc.gc.ca

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