Development and preclinical evaluation of an alphavirus replicon vaccine for influenza.
We used a propagation-defective, single-cycle, alphavirus replicon vector system to produce virus-like replicon particles (VRP) expressing the hemagglutinin (HA) and neuraminidase (NA) proteins from influenza A/Wyoming/03/2003 (H3N2). Efficient production methods were scaled to produce pilot lots of HA VRP and NA VRP and clinical lots of HA VRP. HA VRP-induced high-titered antibody responses in mice, rabbits and rhesus macaques, as measured by ELISA or hemagglutination inhibition (HI) assays, and robust cellular immune responses in mice and rhesus macaques, as measured by IFN-gamma ELISPOT. NA VRP also induced cellular immune responses in mice. A toxicology study with HA VRP and NA VRP in rabbits showed no adverse effects in any parameter. These studies support clinical testing of alphavirus replicon vaccines for influenza.
Hubby
Bolyn
B
AlphaVax, Inc., 2 Triangle Drive, Research Triangle Park, NC 27709, USA.
Talarico
Todd
T
Maughan
Maureen
M
Reap
Elizabeth A
EA
Berglund
Peter
P
Kamrud
Kurt I
KI
Copp
Laura
L
Lewis
Whitney
W
Cecil
Chad
C
Norberg
Pamela
P
Wagner
Jordan
J
Watson
Aubrey
A
Negri
Sarah
S
Burnett
Bruce K
BK
Graham
Andrew
A
Smith
Jonathan F
JF
Chulay
Jeffrey D
JD
D000524:Alphavirus / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007111:Immunity, Cellular; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D051379:Mice; D009439:Neuraminidase / Q000276:immunology*; D011817:Rabbits; D012093:Replicon
D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D009439:Neuraminidase