Effect of inactivation method on the cross-protective immunity induced by whole 'killed' influenza A viruses and commercial vaccine preparations.
We have recently shown that intranasal (i.n.) administration of gamma-irradiated A/PR/8 [A/Puerto Rico/8/34 (H1N1)] protects mice against lethal avian influenza A/Vietnam/1203/2004 (H5N1) and other heterosubtypic influenza A infections. Here, we used gamma-irradiated, formalin- and UV-inactivated A/PC [A/Port Chalmers/1/73 (H3N2)] virus preparations and compared their ability to induce both homologous and heterosubtypic protective immunity. Our data show that, in contrast to i.n. vaccination with formalin- or UV-inactivated virus, or the present commercially available trivalent influenza vaccine, a single dose of gamma-ray-inactivated A/PC (gamma-A/PC) conferred significant protection in mice against both homologous and heterosubtypic virus challenges. A multiple immunization regime was required for formalin-inactivated virus preparations to induce protective immunity against a homotypic virus challenge, but did not induce influenza A strain cross-protective immunity. The highly immunogenic gamma-A/PC, but not formalin- or UV-inactivated A/PC, nor the currently available subvirion vaccine, elicited cytotoxic T-cell responses that are most likely responsible for the cross-protective and long-lasting immunity against highly lethal influenza A infections in mice. Finally, freeze-drying of gamma-A/PC did not affect the ability to induce cross-protective immunity.
Viral Immunology and Molecular Virology, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
Yoichi
Y
Furuya
Matthias
M
Regner
Mario
M
Lobigs
Aulikki
A
Koskinen
Arno
A
Müllbacher
Mohammed
M
Alsharifi
D000818:Animals; D001835:Body Weight; D056738:Cross Protection; D005260:Female; D005557:Formaldehyde / Q000633:toxicity; D005720:Gamma Rays; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects / Q000276:immunology* / Q000528:radiation effects; D007252:Influenza Vaccines / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014466:Ultraviolet Rays; D015164:Vaccines, Inactivated / Q000276:immunology; D019562:Viral Load; D038301:Virus Inactivation
D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D005557:Formaldehyde