7/14/2014 1 1 Safety and Immunogenicity of a Recombinant Virus-Like Particle Influenza A(H7N9) Vaccine With and Without a Saponin-based Adjuvant 06 May 2014 Louis Fries, MD Vice President, Chief Medical Officer Novavax, Inc. 2 Influenza Virus Vaccine VLPs HA and NA spikes M1 internal RNA genome No influenza genetic material VLPs Mimic Influenza Virus, but are Non-Infectious Lipid bilayer 3 3 Recombinant Baculovirus VLP Vaccine Generation of baculovirus cell-based VLPs Genes are synthesized based on GISAID sequence data • Condon-optimized for expression in insect cells • HA – Exact amino acid match to human isolates – Expressed as HA0 • NA – Expressed in a 1:3 to 5 ratio to HA, enzymatically-active • M1 – Avian M1 used for all strains – Supports maximal productivity in insect cells VLPs bud from Sf9 cell membrane lipid rafts No amino acid changes resulting from egg passage Ready generation of purified HA and NA reagents 4 Minutes 13 14 15 16 17 18 19 20 21 22 23 24 AU 0.000 0.005 0.010 0.015 Before Deglycosylation HA M1 HA,NA M1 NA Minutes 13 14 15 16 17 18 19 20 21 22 23 24 AU 0.0000 0.0002 0.0004 0.0006 0.0008 0.0010 After Deglycosylation HA~34% M1 PNGase F NA~8% Reducing the Complexity of Capillary Gel Electrophoresis by Deglycosylation
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7/14/2014
1
1
Safety and Immunogenicity of a Recombinant
Virus-Like Particle Influenza A(H7N9) Vaccine
With and Without a Saponin-based Adjuvant
06 May 2014
Louis Fries, MD
Vice President, Chief Medical Officer
Novavax, Inc.
2
Influenza Virus Vaccine VLPs
HA and NA spikes
M1 internal
RNA genome
No influenza genetic material
VLPs Mimic Influenza Virus, but are Non-Infectious
Lipid bilayer
3 3
Recombinant Baculovirus VLP Vaccine
Generation of baculovirus cell-based VLPs
Genes are synthesized based on GISAID sequence data
• Condon-optimized for expression in insect cells
• HA
– Exact amino acid match to human isolates
– Expressed as HA0
• NA
– Expressed in a 1:3 to 5 ratio to HA, enzymatically-active
• M1
– Avian M1 used for all strains
– Supports maximal productivity in insect cells
VLPs bud from Sf9 cell membrane lipid rafts
No amino acid changes resulting from egg passage
Ready generation of purified HA and NA reagents
4
Minutes
13 14 15 16 17 18 19 20 21 22 23 24
AU
0.000
0.005
0.010
0.015Before Deglycosylation
HA
M1
HA,NA
M1
NA
Minutes
13 14 15 16 17 18 19 20 21 22 23 24
AU
0.0000
0.0002
0.0004
0.0006
0.0008
0.0010 After Deglycosylation HA~34% M1
PNGase F NA~8%
Reducing the Complexity of Capillary Gel Electrophoresis
2: Common post-vaccinal events solicited by diary for 7 days after each dose; each subject enters the analysis here at his/her worst severity grade after either dose.
12 12
Additional Safety Data
• Local solicited adverse events were primarily mild to moderate
injection site pain, which did not escalate in frequency or
severity after the second dose.
• Transient myalgia, arthralgia, headache and fatigue are the
major contributors to systemic reactogenicity.
‒ Overall, the rate of severe complaints is low, and the few oral
temperature elevations reported are <38.5⁰C.
• Clinical laboratory abnormalities typically transient, with no clear
temporal relation to treatment.
• Since Day 35, there have been 5 additional SAEs
‒ Span placebo, unadjuvanted, and adjuvanted vaccines groups
‒ Various body systems, none deemed related.
7/14/2014
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A/Anhui/1/2013 HAI Titer Responses at Days 21 and 35