716. M2e-Flagellin Conjugate Influenza Vaccine IgG Responses in Humans
Session: Poster Abstract Session: Vaccine Studies, Adjuvants, and Discovery
Friday, October 21, 2011
Room: Poster Hall B1
University of Colorado Denver, School of Medicine

Denver, Colorado, USA

VaxInnate, Inc.

New Jersey, USA

 

M2e-Flagellin Conjugate Influenza Vaccine IgG Responses in Humans.

Richard Sullivan, Jeremy Rahkola, Uma Kavita, Lynda Tussey PhD, David N. Taylor MD, Myron Levin MD, Edward N. Janoff MD.  

Background: We report significant antibody responses to vaccination with a highly conserved but poorly immunogenic influenza protein, M2e (the surface portion of the M2 proton channel). To improve the human antibody response to M2e, we characterized the ability of flagellin, an innate immune agonist, to serve as an adjuvant to generate immune responses to M2e (M2e-flagellin).

Methods: We measured levels of M2e-specific serum IgG, recognition by IgG of the 6 known human M2e peptide sequences, primary epitope recognition, and changes in apparent avidity in 20 subjects from a phase I clinical trial.  Subjects received 2 vaccine doses (days 0 and 28), of either 1µg intramuscularly (IM) or 2µg subcutaneously (SC).

Results: Most preimmunization levels were low (<0.02mcg/mL), but by day 42, mean specific IgG increased to 1.7 µg/ml (IM) and 3.5 µg/mL (SC) (day 0 vs day 42, P<0.0001). Specific IgG on day 42 showed comparable recognition of the 4 “classical” M2e peptides that represent >99% of the known M2e sequences. Lower but detectable binding was observed to the current pandemic H1N1 (swine) M2e but not M2e from clinical H5N1 (avian) strains.  IgG bound most robustly to 1 of 2 known B cell epitopes (aa 6-14), which has sequence heterogeneity with pandemic H1N1 and especially, H5N1. The apparent avidity of M2e IgG ranged from 3.5 X10-6 to 1.55 X 10-7 Kd. with a trend toward increasing avidity from day 14 through day 42.  

Conclusion: We conclude that, despite very low levels of M2e-specific IgG in healthy adults prior to vaccination,  the M2e-flagellin conjugate vaccine elicits significant increases in specific IgG in healthy adults that recognize diverse M2e sequences, but  with a more limited capacity to bind to more divergent M2e peptides recently introduced into the human population from animal reservoirs. Thus, innate immune agonists, such as flagellin, can be used to enhance responses to biologically relevant but poorly immunogenic antigens.


Subject Category: I. Adult and Pediatric Vaccines

Richard Sullivan, BS1, Jeremy Rahkola, BS2, Uma Kavita, PhD3, Lynda Tussey, PhD3, David Taylor, MD4, Myron Levin, MD5 and Edward Janoff, MD6, (1)University of Colorado, Aurora, CO, (2)University of Colorado; DVAMC, Denver, CO, (3)VaxInnate Corp, Cranbury, NJ, (4)Vaxinnate, Cranbury, NJ, (5)University of Colorado Anschutz Medical Campus, Aurora, CO, (6)University of Colorado Denver, Aurora, CO

Disclosures:

R. Sullivan, Vax: Collaborator, Educational grant

J. Rahkola, None

U. Kavita, VaxInnate: Employee, Salary

L. Tussey, VaxInnate: Employee, Salary

D. Taylor, VaxInnate: Employee, Salary

M. Levin, None

E. Janoff, VaxInnate: Collaborator, Research grant

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.