Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine.
BACKGROUND
Avian H5N1 influenza A virus is an emerging pathogen with the potential to cause substantial human morbidity and mortality. We evaluated the ability of currently licensed seasonal influenza vaccine to confer cross-protection against highly pathogenic H5N1 influenza virus in mice.


METHODS
BALB/c mice were inoculated 3 times, either intranasally or subcutaneously, with the trivalent inactivated influenza vaccine licensed in Japan for the 2005-2006 season. The vaccine included A/NewCaledonia/20/99 (H1N1), A/NewYork/55/2004 (H3N2), and B/Shanghai/361/2002 viral strains and was administered together with poly(I):poly(C(12)U) (Ampligen) as an adjuvant. At 14 days after the final inoculation, the inoculated mice were challenged with either the A/HongKong/483/97, the A/Vietnam/1194/04, or the A/Indonesia/6/05 strain of H5N1 influenza virus.


RESULTS
Compared with noninoculated mice, those inoculated intranasally manifested cross-reactivity of mucosal IgA and serum IgG with H5N1 virus, as well as both a reduced H5N1 virus titer in nasal-wash samples and increased survival, after challenge with H5N1 virus. Subcutaneous inoculation did not induce a cross-reactive IgA response and did not afford protection against H5N1 viral infection.


CONCLUSIONS
Intranasal inoculation with annual influenza vaccine plus the Toll-like receptor-3 agonist, poly(I):poly(C(12)U), may overcome the problem of a limited supply of H5N1 virus vaccine by providing cross-protective mucosal immunity against H5N1 viruses with pandemic potential.
Ichinohe
Takeshi
T
Department of Pathology, National Institute of Infectious Diseases, Musashimurayama-Shi, Tokyo, Japan.
Tamura
Shin-Ichi
S
Kawaguchi
Akira
A
Ninomiya
Ai
A
Imai
Masaki
M
Itamura
Shigeyuki
S
Odagiri
Takato
T
Tashiro
Masato
M
Takahashi
Hidehiro
H
Sawa
Hirofumi
H
Mitchell
William M
WM
Strayer
David R
DR
Carter
William A
WA
Chiba
Joe
J
Kurata
Takeshi
T
Sata
Tetsutaro
T
Hasegawa
Hideki
H
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D011070:Poly I-C / Q000494:pharmacology; D011072:Poly U / Q000494:pharmacology; D020545:Respiratory Mucosa; D013601:T-Lymphocytes / Q000502:physiology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D011072:Poly U; C047490:poly(I).poly(c12,U); D011070:Poly I-C