Giuseppe
Emeritus
J Infect Dis. 2009 Dec 15;200(12):1874-1883.
A Live Attenuated H1N1 M1 Mutant Provides Broad Cross-Protection against Influenza A Viruses, Including Highly Pathogenic A/Vietnam/1203/2004, in Mice.
Xie H, Liu TM, Lu X, Wu Z, Belser JA, Katz JM, Tumpey TM, Ye Z. - Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland; 2Influenza Division, United States Centers for Diseases Control and Prevention, Atlanta, Georgia.
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.
PMID: 19909080 [PubMed - as supplied by publisher]
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A Live Attenuated H1N1 M1 Mutant Provides Broad Cross-Protection against Influenza A Viruses, Including Highly Pathogenic A/Vietnam/1203/2004, in Mice.
Xie H, Liu TM, Lu X, Wu Z, Belser JA, Katz JM, Tumpey TM, Ye Z. - Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccine Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Bethesda, Maryland; 2Influenza Division, United States Centers for Diseases Control and Prevention, Atlanta, Georgia.
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.
PMID: 19909080 [PubMed - as supplied by publisher]
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