Cross-protection against H5N1 influenza virus infection is afforded by intranasal inoculation with seasonal trivalent inactivated influenza vaccine

J Infect Dis. 2007 Nov 1;196(9):1313-20. doi: 10.1086/521304. Epub 2007 Oct 5.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Intranasal
  • Animals
  • Antibodies, Viral
  • Female
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / prevention & control*
  • Poly I-C / pharmacology
  • Poly U / pharmacology
  • Respiratory Mucosa
  • T-Lymphocytes / physiology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Influenza Vaccines
  • Poly U
  • poly(I).poly(c12,U)
  • Poly I-C