Abstract Title
Next Generation Oral Norovirus Vaccine Candidate Generates Improved Immune Responses to GI.I and GII.4 strains in Humans
Presenter
Sean N. Tucker, Vaxart, Inc
Co-Author(s)
Sean N. Tucker1, Becca A. Flitter1, Nicholas J. Bennett1, Maria D. Apkarian1, Colin A. Lestor1, Nick P. D’Amato1, James F. Cummings1, 1Vaxart, Inc.; South San Francisco, CA 94080, USA
Abstract
Background: Demonstrating clear immune correlates for norovirus vaccine candidates has been challenging, but would accelerate clinical development. Vaxart conducted a successful phase 2b placebo-controlled GI.1 challenge study. Machine learning analyses identified norovirus blocking antibody assay (NBAA) and fecal IgA as immune correlates of protection. Improvements in the underlying technology were incorporated into a bivalent GI.1/GII.4 Next generation vaccine candidate (NGV) to improve antigen expression over the bivalent first generation candidate (1GV).
Methods: An open-label phase 1 trial of vaccine candidates was conducted to compare immunogenicity and safety. Healthy adult subjects were enrolled sequentially in three Arms: Arm1-NGV, 1e10 each strain; Arm 2-1GV, 1e11 each strain; Arm 3-NGV, 1e11 each strain. N=20 per Arm. Safety and NBAA titers were assessed as primary outcomes. Cross-reactivity was assessed by a multiplex MSD antibody binding assay.
Results: All confirmed solicited symptoms and unsolicited events were of mild to moderate severity and the number and severity of symptoms were similar between study arms. No serious adverse events or adverse events of special interest were reported. The NGV improved GI.1 and GII.4 NBAA titers compared to the 1GV. An NBAA Geometric Fold Rise (GMFR) of 5.1 of GI.1 was observed for Arm 1 and 5.4 for Arm 3, which was improved over the Arm 2 GMFR of 2.2. Similarly, a GMFR of 3.5 in Arm 1 and 3.7 in Arm 3 for GII.4 was improved over 1.9 observed in Arm 2. Statistical significance of <0.05 was achieved for the 1e11 NGV against both strains. The NGV also improved cross-reactivity to multiple norovirus antigens.
Conclusions: The oral NGV improved immunogenicity without any notable impact on vaccine safety.
Methods: An open-label phase 1 trial of vaccine candidates was conducted to compare immunogenicity and safety. Healthy adult subjects were enrolled sequentially in three Arms: Arm1-NGV, 1e10 each strain; Arm 2-1GV, 1e11 each strain; Arm 3-NGV, 1e11 each strain. N=20 per Arm. Safety and NBAA titers were assessed as primary outcomes. Cross-reactivity was assessed by a multiplex MSD antibody binding assay.
Results: All confirmed solicited symptoms and unsolicited events were of mild to moderate severity and the number and severity of symptoms were similar between study arms. No serious adverse events or adverse events of special interest were reported. The NGV improved GI.1 and GII.4 NBAA titers compared to the 1GV. An NBAA Geometric Fold Rise (GMFR) of 5.1 of GI.1 was observed for Arm 1 and 5.4 for Arm 3, which was improved over the Arm 2 GMFR of 2.2. Similarly, a GMFR of 3.5 in Arm 1 and 3.7 in Arm 3 for GII.4 was improved over 1.9 observed in Arm 2. Statistical significance of <0.05 was achieved for the 1e11 NGV against both strains. The NGV also improved cross-reactivity to multiple norovirus antigens.
Conclusions: The oral NGV improved immunogenicity without any notable impact on vaccine safety.