1970. Phase 1 Clinical Trial of Intranasal Immunization with M2-deficient, Single Replication, Live Influenza Vaccine (M2SR): Safety and Immune Response in Adults
Session: Poster Abstract Session: Clinical Trials
Saturday, October 6, 2018
Room: S Poster Hall

Background: Influenza vaccines are needed with greater effectiveness and breadth of coverage. FluGen is developing M2SR (M2 deficient Single Replication), an investigational, live virus vaccine. M2SR contains the internal proteins of donor A/Puerto Rico/8/34 and hemagglutinin (HA) and neuraminidase (NA) selected from targeted Type A influenza strains. M2SR undergoes only a single round of infection in the respiratory epithelium but evokes an immune response profile similar to wild-type influenza viruses. In influenza naïve and pre-immune ferrets, M2SR protects against multiple influenza A subtypes.

Methods: A Phase 1, first-in-human, randomized, placebo-control study (FluGen-H3N2-V001; ClinicalTrials.gov identifier NCT02822105) was conducted at a single USA site, with 96 adults, ages 18-49 years. Study vaccine contained HA and NA from A/Brisbane/10/2007 (H3N2). Study volunteers received a single intranasal (IN) inoculation with either M2SR at dose levels of 106, 107 or 108 TCID50 or saline placebo (N=24/cohort). Study subjects were evaluated for virus replication and solicited local and systemic reactions for 7 days, all adverse events (AE) for 28 days and serious AE (SAE) for 180 days.

Results: No infectious virus was detected in nasal swabs from any vaccinated subject. The most commonly reported AE was mild nasal rhinorrhea/congestion during the first 7 days after vaccination (Figure 1). No subject had fever or a severe reaction to the vaccine. No SAEs were reported. At least one AE was reported among 29%, 58%, and 83% of M2SR subjects administered 106, 107, or 108 TCID50, respectively, and 46% among placebo subjects. There were no notable imbalances among study groups for other events. T- and B-cell responses, including influenza-specific serum and mucosal antibody responses were detected at a significantly higher frequency among vaccine than placebo subjects (Figure 2).

Conclusion: M2SR vaccine was safe and well tolerated at all dose levels, generated a dose-response effect for humoral (HA antibody) and mucosal antibodies against both homologous and heterologous influenza variants, and elicited robust T-cell responses. No infectious virus was detected in nasal swabs from any vaccinated subject.

Figure 1. Common Adverse Events First 7 Days Post-Vaccination

 

Figure 2. Influenza-specific Immune responses

 

 

Joseph Eiden, MD, PhD1, Gilad Gordon, MD2, Carlos Fierro, MD3, Robert Belshe, MD4, Harry Greenberg, MD, FIDSA5, Dan Hoft, MD, PhD4, Yasuko Hatta, DVM, PhD6, Michael Imboden, PhD6, Mike Moser, PhD6, Renee Herber, BS6, David Boltz, PhD7, Magdalena Tary-Lehmann, MD, PhD8, Yoshihiro Kawaoka, DVM, PhD9, Gabriele Neumann, PhD9, Paul Radspinner, MBA6, Roger Aitchison, ScM10 and Pamuk Bilsel, PhD6, (1)Celyn Consulting, LLC, Lewes, DE, (2)ORRA Group, LLC, Boulder, CO, (3)Johnson County Clin-Trials, Lenexa, KS, (4)Saint Louis University, St. Louis, MO, (5)Stanford University, Stanford, CA, (6)FluGen, Inc., Madison, WI, (7)IIT Research Institute, Chicago, IL, (8)Cellular Technology Limited, Shaker Heights, OH, (9)Influenza Research Institute, University of Wisconsin, Madison, WI, (10)North Rim Consulting, Denver, CO

Disclosures:

J. Eiden, FluGen, Inc.: Consultant , Consulting fee and Stock Options .

G. Gordon, FluGen: Consultant , Consulting fee .

C. Fierro, FluGen: Investigator , Fee for service .

R. Belshe, FluGen: Consultant , Consulting fee and Stock Options .

H. Greenberg, FluGen: Consultant , Consulting fee and Stock OpTions .

D. Hoft, FluGen: Research Contractor , Fee for service .

Y. Hatta, FluGen: Employee , Salary and Stock Options .

M. Imboden, FluGen: Employee , Salary and Stock Options .

M. Moser, FluGen: Employee , Salary and Stock Options .

R. Herber, FluGen: Employee , Salary and Stock Options .

D. Boltz, FluGen: Research Contractor , fee for service .

M. Tary-Lehmann, FluGen: Research Contractor , Fee for service . CTL: Founder and Owner , Salary .

Y. Kawaoka, FluGen: Founder , Stock Options .

G. Neumann, FluGen: Founder , Stock Options .

P. Radspinner, FluGen: Board Member and Founder , Salary and Stock Options .

R. Aitchison, FluGen: Consultant , Consulting fee .

P. Bilsel, FluGen: Employee , Salary and Stock Options .

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