Comparative trial vs Fluvac Innovator ACVIM 2011

Comparative trial vs Fluvac Innovator ACVIM 2011

Protection from contemporary
equine influenza virus by
commercial vaccines
Ann D. Sellers
Gabriele A. Landolt
Hugh G.G. Townsend
John Tuttle
Robert M. Stenbom
D. Paul Lunn
Equine influenza virus
A equine 1 virus or A/equine/Prague/56
A equine 2 virus or A/equine/Miami/63
A/equine/Ohio /03
Epidemiologic features
shed for 7-10 days (2-3 if not naive)
no latent infection, recirculates in population
Hemagglutinin structure
HA glycoprotein
Homotrimer
Antigenic drift
Antigenic shift
HA1 Phylogenetic Tree
A/EQ/MIAMI/1963
A/EQ/FONTAINBLEAU/1979
A/EQ/NEWMARKET/1979
A/EQ/KENTUCKY/2/81
Vaccines:
• Fluvac Innovator®
– A/EQ/Kentucky/1997
• Adjuvant: Metastim®
• Calvenza EIV®
– A/EQ/Newmarket/2/1993
– A/EQ/Kentucky/1995
– A/EQ/Ohio/2003
• Adjuvant: Carbopol®
Challenge virus:
– A/EQ/Colorado/1/2007
Pre-divergence
A/EQ/SWITZERLAND/P112/2007
A/EQ/SUSSEX/1989
A/EQ/GROBOIS/1998
A/EQ/LINCOLNSHIRE/1/2002
A/EQ/ABOYNE/2005
A/EQ/ROME/5/1991
A/EQ/HONG KONG/1992
A/EQ/LAMBOURN/1992
A/EQ/NEWMARKET/2/1993
A/EQ/KENTUCKY/1/1992
A/EQ/ALASKA/1/1991
A/EQ/NEWMARKET/1/1993
A/EQ/CHESHIRE/1/2006
A/EQ/KENTUCKY/1998
A/EQ/LONQUEN/1/2006
A/EQ/KENTUCKY/1997
A/EQ/NEWMARKET/5/2003
A/EQ/LINCOLNSHIRE/2006
A/EQ/ESSEX/1/2005
A/EQ/SOUTHAMPTON/1/2006
A/EQ/LANARK/2006
A/EQ/WILDESHAUSEN/1/2008
A/EQ/CHESHIRE/3/2007
A/EQ/WORCESTERSHIRE/1/2008
A/EQ/NEWMARKET/2007
A/EQ/PERTHSHIRE/1/2009
A/EQ/YORKSHIRE/3/2009
A/EQ/RICHMOND/1/2007
A/EQ/RICHMOND/2/2007
A/EQ/SOUTHAMPTON/1/2007
A/EQ/CHESHIRE/2/2007
A/EQ/LEICESTERSHIRE/1/2008
A/EQ/HEILONGJIANG/10/2008
A/EQ/LIAONING/9/2008
A/EQ/MONGOLIA/1/2008
A/EQ/XINJIANG/5/2007
A/EQ/INNER-MONGOLIA/8/2008
A/EQ/HUBEI/6/2008
A/EQ/SOUTH AFRICA/4/2003
A/EQ/OHIO/03
A/EQ/KENTUCKY/9/2004
A/EQ/WISCONSIN/1/2003
A/EQ/PENSYLVANNIA/1/2007
A/EQ/IBARAKI/1/2007
A/EQ/KANAZAWA/1/2007
A/EQ/FLORIDA/2/2006
A/EQ/CALIFORNIA/2/2007
A/EQ/CALIFORNIA/1/2007
A/EQ/COLORADO/1/2007
A/EQ/OKLAHOMA/l/2008
A/EQ/KENTUCKY/7/2007
A/EQ/KENTUCKY/4/2007
A/EQ/VIRGINIA/1/2008
A/EQ/LINCOLNSHIRE/1/2007
A/EQ/KENTUCKY1//09
A/EQ/OHIO/1/2008
A/EQ/EGYPT/6066/2008
A/EQ/OHIO/1/2009
A/EQ/CHESHIRE/1/2009
A/EQ/BRIDGEND/1/2009
A/EQ/HEREFORDSHIRE/1/2009
A/EQ/MONMOUTHSHIRE/1/2009
A/EQ/NOTTINGHAMSHIRE/1/2009
A/EQ/LANARKSHIRE/1/2009
A/EQ/DORSET/1/2009
Eurasian
American
Florida
Clade 2
Florida
Clade 1
2007
2008
2009
courtesy of Dr. Debs Elton, AHT & Heidi Pecoraro, CSU
Study design
Comparison of two contemporary killed vaccines in
a challenge protection trail
Calvenza EIV®
Fluvac Innovator®
Blinded, randomized, controlled challenge trial
Challenge 6 months after 3-series primary
vaccination
Nebulized aerosol:
A/EQ/Colorado / 2007 (108 EID50)
Study design
Yearling ponies
10 controls
10 in each vaccine group
Clinical Score
Rectal temperature
Body weight
V1 V2
Viral shedding
Antibody response
Vaccination reactions
V3
-4 -3 -2 -1 0
Ch
1
2
Months
3
4
5
6
7
Clinical Score
Clinical sign
Coughing
Nasal discharge
Dyspnoea
Depression
Anorexia
Description
No cough
Coughing once
Coughing twice or more
No discharge
Serous discharge
Mucopurulent discharge
Profuse mucopurulent discharge
No dyspnea (£ 36/min)
Mild dyspnea (> 36/min)
Severe dyspnea
No depression
Depression.
Absent
Present
Score
0
1
2
0
1
2
3
0
1
2
0
1
0
1
Statistical Analysis
Animal data was summed over time course of experiment
Summed data ranked & analyzed by one-way ANOVA
Means of the ranks were compared using Tukey’s test
Significance reported when p-values ≤ 0.05
Post-challenge data compared from Day 1 – 10
Serology data compared up to Challenge (Day 295)
Data displayed as medians if not normally distributed
Results
Both vaccine groups significantly different from
controls, but not from each other: p = 0.001
Both vaccine groups significantly different from
controls, but not from each other: p = 0.01
Both vaccine groups significantly different from
controls, but not from each other: p = 0.01
Calvenza significantly different from controls:
p = 0.0001
Calvenza significantly different from Innovator:
p = 0.0007
Innovator not significantly different from controls: p = 0.114
Calvenza significantly different from controls:
p = 0.0001
Calvenza significantly different from Innovator:
p = 0.0007
Innovator not significantly different from controls: p = 0.114
All three groups significantly different
from each other: p = 0.001
V1 V2
V3
Ch
All three groups significantly different
from each other: p = 0.001
V1 V2
V3
Ch
Summary
Excellent clinical protection at 6 months
One vaccine provided partial protection from
viral shedding at 6 months post-vaccination
Influenza-specific antibody responses were
different between the two vaccines
Further analysis of antibody responses to follow
HA1 Phylogenetic Tree
A/EQ/MIAMI/1963
A/EQ/FONTAINBLEAU/1979
A/EQ/NEWMARKET/1979
A/EQ/KENTUCKY/2/81
Vaccines:
• Fluvac Innovator®
– A/EQ/Kentucky/1997
• Adjuvant: Metastim®
• Calvenza EIV®
– A/EQ/Newmarket/2/1993
– A/EQ/Kentucky/1995
– A/EQ/Ohio/2003
• Adjuvant: Carbopol®
Challenge virus:
– A/EQ/Colorado/1/2007
Pre-divergence
A/EQ/SWITZERLAND/P112/2007
A/EQ/SUSSEX/1989
A/EQ/GROBOIS/1998
A/EQ/LINCOLNSHIRE/1/2002
A/EQ/ABOYNE/2005
A/EQ/ROME/5/1991
A/EQ/HONG KONG/1992
A/EQ/LAMBOURN/1992
A/EQ/NEWMARKET/2/1993
A/EQ/KENTUCKY/1/1992
A/EQ/ALASKA/1/1991
A/EQ/NEWMARKET/1/1993
A/EQ/CHESHIRE/1/2006
A/EQ/KENTUCKY/1998
A/EQ/LONQUEN/1/2006
A/EQ/KENTUCKY/1997
A/EQ/NEWMARKET/5/2003
A/EQ/LINCOLNSHIRE/2006
A/EQ/ESSEX/1/2005
A/EQ/SOUTHAMPTON/1/2006
A/EQ/LANARK/2006
A/EQ/WILDESHAUSEN/1/2008
A/EQ/CHESHIRE/3/2007
A/EQ/WORCESTERSHIRE/1/2008
A/EQ/NEWMARKET/2007
A/EQ/PERTHSHIRE/1/2009
A/EQ/YORKSHIRE/3/2009
A/EQ/RICHMOND/1/2007
A/EQ/RICHMOND/2/2007
A/EQ/SOUTHAMPTON/1/2007
A/EQ/CHESHIRE/2/2007
A/EQ/LEICESTERSHIRE/1/2008
A/EQ/HEILONGJIANG/10/2008
A/EQ/LIAONING/9/2008
A/EQ/MONGOLIA/1/2008
A/EQ/XINJIANG/5/2007
A/EQ/INNER-MONGOLIA/8/2008
A/EQ/HUBEI/6/2008
A/EQ/SOUTH AFRICA/4/2003
A/EQ/OHIO/03
A/EQ/KENTUCKY/9/2004
A/EQ/WISCONSIN/1/2003
A/EQ/PENSYLVANNIA/1/2007
A/EQ/IBARAKI/1/2007
A/EQ/KANAZAWA/1/2007
A/EQ/FLORIDA/2/2006
A/EQ/CALIFORNIA/2/2007
A/EQ/CALIFORNIA/1/2007
A/EQ/COLORADO/1/2007
A/EQ/OKLAHOMA/l/2008
A/EQ/KENTUCKY/7/2007
A/EQ/KENTUCKY/4/2007
A/EQ/VIRGINIA/1/2008
A/EQ/LINCOLNSHIRE/1/2007
A/EQ/KENTUCKY1//09
A/EQ/OHIO/1/2008
A/EQ/EGYPT/6066/2008
A/EQ/OHIO/1/2009
A/EQ/CHESHIRE/1/2009
A/EQ/BRIDGEND/1/2009
A/EQ/HEREFORDSHIRE/1/2009
A/EQ/MONMOUTHSHIRE/1/2009
A/EQ/NOTTINGHAMSHIRE/1/2009
A/EQ/LANARKSHIRE/1/2009
A/EQ/DORSET/1/2009
Eurasian
American
Florida
Clade 2
Florida
Clade 1
2007
2008
2009
courtesy of Dr. Debs Elton, AHT & Heidi Pecoraro, CSU
Influenza - killed vaccines
2 (3) dose primary for killed
one month, and then 3-6 month intervals may be optimal
Boost at 6-12 month intervals
6 months for at risk populations
timed 4-6 weeks prior to foaling
2-3 weeks prior to exposure
Start at 6 months of age
Product differences ….
They are all effective at some level
There are performance differences
Strain / antigen quality-quantity / Adjuvant
with thanks to…..
James Gilkerson,
University of Melbourne
Debs Elton,
Animal Health Trust,
Cambridge
Ann Cullinane,
Irish Equine Centre