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The emergence of novel influenza A H1N1 and highly pathogenic avian influenza (HPAI) H5N1 viruses underscores the urgency of developing efficient vaccines against an imminent pandemic. M(NLS-88R) (H1N1), an A/WSN/33 mutant with modifications in the multibasic motif 101RKLKR105 of the matrix (M1) protein and its adjacent region, was generated by reverse genetics. The M(NLS-88R) mutant had in vitro growth characteristics similar to those of wild-type A/WSN/33 (wt-WSN), but it was attenuated in mice. Vaccination with M(NLS-88R) not only fully protected mice from lethal homologous challenges but also prevented mortality caused by antigenically distinct H3N2 and H5N1 viruses. M(NLS-88R)-induced homologous protection was mainly antibody dependent, but cellular immunity was also beneficial in protecting against sublethal wt-WSN infection. Adoptive transfer studies indicated that both humoral and cellular immune responses were crucial for M(NLS-88R)-induced heterologous protection. Our study suggests an alternative approach to attenuate wt influenza viruses for the development of a pandemic vaccine with broad cross-protection. [ABSTRACT FROM AUTHOR]

Since 1997, outbreaks of highly pathogenic (HP) H5N1 and circulation of H9N2 viruses among domestic poultry in Asia have posed a threat to public health. To better understand the extent of transmission of avian influenza viruses (AIV) to humans in Asia, we conducted a cross-sectional virologic study in live bird markets (LBM) in Hanoi, Vietnam, in October 2001. Specimens from 189 birds and 18 environmental samples were collected at 10 LBM. Four influenza A viruses of the H4N6 (n = 1), H5N2 (n = 1), and H9N3 (n = 2) subtypes were isolated from healthy ducks for an isolation frequency of over 30% from this species. Two HSNI viruses were isolated from healthy geese. The hemagglutinin (HA) genes of these H5N1 viruses possessed multiple basic amino acid motifs at the cleavage site, were HP for experimentally infected chickens, and were thus characterized as HP AIV. These HA genes shared high amino acid identities with genes of other H5N1 viruses isolated in Asia during this period, but they were genetically distinct from those of H5N1 viruses isolated from poultry and humans in Vietnam during the early 2004 outbreaks. These viruses were not highly virulent for experimentally infected ducks, mice, or ferrets. These results establish that HP H5N1 viruses with properties similar to viruses isolated in Hong Kong and mainland China circulated in Vietnam as early as 2001, suggest a common source for H5N1 viruses circulating in these Asian countries, and provide a framework to better understand the recent widespread emergence of HP H5N1 viruses in Asia. [ABSTRACT FROM AUTHOR]