750. Formulation of Orally and Intranasally Administered Influenza Vaccine in Cochleate Lipid-Crystal Nano-Particles Significantly Enhances Immune Response in a Murine Models of Influenza
Session: Poster Abstract Session: Vaccines: New and Novel
Thursday, October 27, 2016
Room: Poster Hall
Background: Cochleate Lipid-crystal Nano-particle (LCNP) technology has demonstrated non-invasive delivery of a broad range of compounds. New formulations of the influenza vaccine with this technology may provide less invasive administration options and increase delivery efficiency.

Objectives: To demonstrate that oral/intranasal dosed LCNP formulations of the influenza vaccine (LCNP HA/NA) provide significant antibody responses with associated viral protection at lower doses.

Methods: LCNP HA/NAs were prepared by incorporating extracted influenza virion hemagglutinin antigen (HA) and neuraminidase antigen (NA) protein into the cochleate lipid-crystal matrix.In three experiments, mice were dosed at week zero, three, and 13-15 at full, full and quarter of the indicated dose level respectively. Exp1: FLU-LCNP HA/NA formulation was administered to BALB/c mice comparing 50µg IM to oral dosing. Antibody isotype plasma titers were measured at week 14. Exp2: assess virus in lungs and trachea after oral dosing of LCNP HA/NA formulations at 100µg, 50µg, 25µg, 12.5µg, 6µg, 3µg, and 0µg, followed by intranasal viral challenge at week 16. Exp3: neutralizing plasma antibody titers were assessed at week 20 comparing a commercial influenza vaccine versus LCNP of this commercial vaccine after intranasal doses of 1.2µg and 12 µg.

Results: Exp1: intramuscular injection resulted in higher IgM and IgG antibody isotype titers than oral administration, with both reaching significant levels (IgG titers of 200,000 versus 25,000 respectively). IgA was much higher upon oral than IM dosing (titers 640 oral vs. 10 IM) suggesting strong protection. Exp2 confirmed this level of protection, with full lung protection at doses of 12.5µg and higher and with 22 out of 25 mice receiving 6µg or higher having no virus present in the trachea.Exp3 confirmed the dose efficiency of the cochleate nano-particle formulation with neutralizing antibody titers more than 10x higher than unformulated influenza vaccine at each dose level.

Conclusion: These studies demonstrate that oral/intranasal administration of LCNP influenza vaccines stimulate systemic and mucosal, antibody and cell mediated responses, and provide a high level of protection from viral infection.

Raphael Mannino, PhD and Ruying Lu, BS, Matinas BioPharma, Inc., Bedminster, NJ


R. Mannino, Matinas BioPharma: Employee and Shareholder , Salary

R. Lu, Matinas BioPharma, Inc.: Employee and Shareholder , Salary

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