Publications (8) View all
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Article: Complement-dependent lysis of influenza a virus-infected cells by broadly cross-reactive human monoclonal antibodies.
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ABSTRACT: We characterized human monoclonal antibodies (MAbs) cloned from influenza virus-infected patients and from influenza vaccine recipients by complement-dependent lysis (CDL) assay. Most MAbs active in CDL were neutralizing, but not all neutralizing MAbs can mediate CDL. Two of the three stalk-specific neutralizing MAbs tested were able to mediate CDL and were more cross-reactive to temporally distant H1N1 strains than the conventional hemagglutination-inhibiting and neutralizing MAbs. One of the stalk-specific MAbs was subtype cross-reactive to H1 and H2 hemagglutinins, suggesting a role for stalk-specific antibodies in protection against influenza illness, especially by a novel viral subtype which can cause pandemics.Journal of Virology 12/2011; 85(24):13463-7. · 5.40 Impact Factor -
Article: Pandemic influenza: implications for preparation and delivery of critical care services.
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ABSTRACT: In a 5-week span during the 1918 influenza A pandemic, more than 2000 patients were admitted to Cook County Hospital in Chicago, with a diagnosis of either influenza or pneumonia; 642 patients, approximately 31% of those admitted, died, with deaths occurring predominantly in patients of age 25 to 30 years. This review summarizes basic information on the biology, epidemiology, control, treatment and prevention of influenza overall, and then addresses the potential impact of pandemic influenza in an intensive care unit setting. Issues that require consideration include workforce staffing and safety, resource management, alternate sites of care surge of patients, altered standards of care, and crisis communication.Journal of Intensive Care Medicine 01/2011; 26(6):347-67. -
Article: Dynamics of the CD8 T-cell response following yellow fever virus 17D immunization.
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ABSTRACT: Management of yellow fever is focused on the prevention of illness by the use of the yellow fever virus (YFV) 17D vaccine. The role of neutralizing antibodies in protection is generally accepted with YFV-specific T cells likely contributing to the control of viral replication. We studied CD8(+) T-cell responses to four defined human leucocyte antigen-B35-restricted epitopes in YFV vaccine recipients as a model of the kinetics of cytotoxic T-lymphocyte responses to an acute human viral infection. Multiple features of these epitope-specific responses were analysed after vaccination including magnitude, cytokine production, phenotype and T-cell receptor repertoire. Peak peptide-specific interferon-gamma (IFN-gamma) responses of almost 1% of CD8(+) T cells were seen as early as 2 weeks post-vaccination; however, dominant responses varied between donors. Peptide-specific responses were still detectable at 54 months post-vaccination. Tetramer-positive cells, at high frequencies, were detected as early as 7-9 days, before detectable IFN-gamma-producing cells, suggesting a defect in the functional capacity of some antigen-specific cells early post-vaccination. The predominant memory phenotype of the tetramer-positive population was a differentiated effector (CD45RA(+) CCR7(-) CD62L(-)) phenotype. The T-cell receptor Vbeta analysis revealed a diverse oligoclonal repertoire in tetramer-positive T-cell populations in two individuals. These characteristics of the YFV-specific T-cell response could contribute to vaccine effectiveness.Immunology 09/2009; 128(1 Suppl):e718-27. · 3.32 Impact Factor -
Article: Genome-wide screening of human T-cell epitopes in influenza A virus reveals a broad spectrum of CD4(+) T-cell responses to internal proteins, hemagglutinins, and neuraminidases.
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ABSTRACT: We performed a genome-wide screening for T-cell epitopes using synthetic peptides that encompass all of the influenza A viral proteins, including subtype variants for hemagglutinin (HA; H1, H3, and H5) and neuraminidase (NA; human and avian N1 and N2) proteins, based on the sequence information of recently circulating strains. We identified a total of 83 peptides, 54 of them novel, to which specific T cells were detectable in interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot assays using peripheral blood mononuclear cells from four healthy adult donors. The surface glycoproteins, HA and NA, major components of vaccines, expressed many T-cell epitopes. HA and matrix protein 1 expressed more T-cell epitopes than other viral proteins, most of which were recognized by CD4(+) T cells. We established several cytotoxic CD4(+) T-cell lines from these donors. We also analyzed H1 and H3 HA-specific T-cell responses using the peripheral blood mononuclear cells of 30 hospital workers. Fifty-three percent of donors gave a positive response to H3 HA peptides, whereas 17% gave a positive response to H1 HA peptides. Our genome-wide screening is useful in identifying T-cell epitopes and is complementary to the approach based on the predicted binding peptides to well-studied HLA-A, -B, and -DR alleles.Human immunology 07/2009; 70(9):711-21. · 2.55 Impact Factor -
Article: In vitro evidence that commercial influenza vaccines are not similar in their ability to activate human T cell responses.
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ABSTRACT: We evaluated three commercial trivalent inactivated vaccines (TIVs) from the 2007-2008 season in terms of their ability to elicit in vitro T cell responses. T cell-mediated immunity may offer a more cross-reactive vaccine approach for the prevention of pandemic or epidemic influenza. Human cytotoxic T cell lines demonstrated differences in matrix protein 1 and nucleocapsid protein recognition of autologous target cells. Peripheral blood mononuclear cells stimulated with each of the TIVs showed statistically significant differences between the vaccines in the numbers of IFNgamma producing cells activated. These data suggest that TIV vaccines are not similar in their ability to activate human T cell responses.Vaccine 11/2008; 27(2):319-27. · 3.77 Impact Factor
