Point-of-Use Mixing of Influenza H5N1 Vaccine and MF59 Adjuvant for Pandemic Vaccination Preparedness: Antibody Responses and Safety. A Phase 1 Clinical Trial.
BACKGROUND
Avian influenza A/H5N1 has threatened human health for nearly 2 decades. Avian influenza A vaccine without adjuvant is poorly immunogenic. A flexible rapid tactic for mass vaccination will be needed if a pandemic occurs.


METHODS
A multicenter, randomized, blinded phase 1 clinical trial evaluated safety and antibody responses after point-of-use mixing of influenza A/Indonesia/05/2005 (H5N1) vaccine with MF59 adjuvant. Field-site pharmacies mixed 3.75, 7.5, or 15 mcg of antigen with or without MF59 adjuvant just prior to intramuscular administration on days 0 and 21 of healthy adults aged 18-49 years.


RESULTS
Two hundred and seventy subjects were enrolled. After vaccination, titers of hemagglutination inhibition antibody ≥1:40 were achieved in 80% of subjects receiving 3.75 mcg + MF59 vs only 14% receiving 15 mcg without adjuvant (P < .0001). Peak hemagglutination inhibition antibody geometric mean titers for vaccine + MF59 were ∼65 regardless of antigen dose, and neutralizing titers were 2- to 3-fold higher. Vaccine + MF59 produced cross-reactive antibody responses against 4 heterologous H5N1 viruses. Excellent safety and tolerability were demonstrated.


CONCLUSIONS
Point-of-use mixing of H5N1 antigen and MF59 adjuvant achieved target antibody titers in a high percentage of subjects and was safe. The feasibility of the point-of-use mixing should be studied further.
Mark J
MJ
Mulligan
David I
DI
Bernstein
Sharon
S
Frey
Patricia
P
Winokur
Nadine
N
Rouphael
Michelle
M
Dickey
Srilatha
S
Edupuganti
Paul
P
Spearman
Edwin
E
Anderson
Irene
I
Graham
Diana L
DL
Noah
Brian
B
Mangal
Sonnie
S
Kim
Heather
H
Hill
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Jenifer
J
Whitaker
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
William
W
Emery
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Allison
A
Beck
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Kathy
K
Stephens
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Brooke
B
Hartwell
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Melinda
M
Ogilvie
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Nayoka
N
Rimann
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Eileen
E
Osinski
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Ellen
E
Destefano
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Theda
T
Gajadhar
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Amanda
A
Strudwick
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Karen
K
Pierce
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Lilin
L
Lai
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Ling
L
Yue
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Dongli
D
Wang
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Carl
C
Ying
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Amy
A
Cline
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Tara
T
Foltz
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Nancy
N
Wagner
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Geraldine
G
Dull
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Thomas
T
Pacatte
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Barbara
B
Taggart
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Valerie
V
Johnson
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Logan
L
Haller
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Candi
C
Looney
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Shixiong
S
Li
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Megan
M
May
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Bridgette
B
Myers
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Rachel
R
May
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Lawanda
L
Parker
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Nertaissa
N
Cochran
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Donna
D
Bowen
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Michelle
M
Bell
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Jeffery
J
Scoggins
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Angela
A
Burns
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Claire
C
Stablein
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Mark
M
Wolff
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Bernadette
B
Jolles
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Brenda
B
Leung
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Linda
L
Lambert
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Shy
S
Shorer
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Wendy
W
Buchanan
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Suzanne
S
Murray
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Soju
S
Chang
Department of Medicine, Division of Infectious Diseases , Emory University School of Medicine , Decatur, Georgia.
Richard
R
Gorman
H5N1; MF59; adjuvant; antibody; avian influenza; pandemic preparedness; point-of-use mixing; vaccine