Intranasal immunization with H5N1 vaccine plus Poly I:Poly C12U, a Toll-like receptor agonist, protects mice against homologous and heterologous virus challenge.
The avian H5N1 influenza virus has the potential to cause a new pandemic. Since it is difficult to predict which strain of influenza will cause a pandemic, it is advantageous to produce vaccines that confer cross-protective immunity. Mucosal vaccine administration was reported to induce cross-protective immunity by inducing secretion of IgA at the mucosal surface. Adjuvants can also enhance the development of fully protective mucosal immunity. Here we show that a new mucosal adjuvant, poly I:poly C12U (Ampligen), a Toll-like receptor 3 agonist proven to be safe in a Phase III human trial, is an effective adjuvant for H5N1 influenza vaccination. Intranasal administration of a candidate influenza vaccine with Ampligen resulted in secretion of IgA, and protected mice that were subsequently challenged with homologous A/Vietnam/1194/2004 and heterologous A/HK/483/97 and A/Indonesia/6/2005 virus.
Ichinohe
Takeshi
T
Department of Pathology, National Institute of Infectious Diseases, 4-7-1 Gakuen, Musashimurayama-shi, Tokyo 208-0011, Japan.
Kawaguchi
Akira
A
Tamura
Shin-ichi
S
Takahashi
Hidehiro
H
Sawa
Hirofumi
H
Ninomiya
Ai
A
Imai
Masaki
M
Itamura
Shigeyuki
S
Odagiri
Takato
T
Tashiro
Masato
M
Chiba
Joe
J
Sata
Tetsutaro
T
Kurata
Takeshi
T
Hasegawa
Hideki
H
D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis; D001769:Blood / Q000821:virology; D005260:Female; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017817:Nasal Lavage Fluid / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011070:Poly I-C / Q000008:administration & dosage / Q000276:immunology*; D011072:Poly U / Q000008:administration & dosage / Q000276:immunology*
D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C