Update: influenza activity--United States and worldwide, 1998-99 season, and composition of the 1999-2000 influenza vaccine.
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In collaboration with the World Health Organization (WHO), the WHO international network of collaborating laboratories, and state and local health departments, CDC conducts surveillance to monitor influenza activity and to detect antigenic changes in the circulating strains of influenza viruses. This report summarizes surveillance for influenza in the United States and worldwide during the 1998-99 influenza season and describes the composition of the 1999-2000 influenza vaccine. (+info)
Intranasal administration of peptide vaccine protects human/mouse radiation chimera from influenza infection.
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Influenza virus is characterized by frequent and unpredictable changes of the surface glycoproteins which enable the virus to escape the immune system. Approved vaccines which consist of the whole virus or the surface glycoproteins fail to induce broad specificity protection. We have previously reported that a peptide-based experimental recombinant vaccine which includes conserved epitopes of B and T lymphocytes was efficient in mice, leading to cross-strain, long-term protection. In the present study, this approach was adapted for the design of a human vaccine, based on epitopes recognized by the prevalent HLAs. These epitopes were expressed in Salmonella flagellin and tested for their efficacy in human/mouse radiation chimera in which human peripheral blood mononuclear cells (PBMC) are functionally engrafted. The vaccinated mice demonstrated clearance of the virus after challenge and resistance to lethal infection. The production of virus-specific human antibodies was also higher in this group. Control groups of either non-vaccinated, or vaccinated mice which had not been engrafted with the human PBMC, did not exhibit the protective immune response. FACS analysis showed that most human cells in the transplanted mice are CD8(+) and CD4(+). Hence, it may be concluded: (i) that the protection involves cellular mechanisms, but is most probably accomplished without direct lysis of influenza-infected pulmonary cells by cytotoxic T lymphocytes, but rather via a cytokine-mediated mechanism, (ii) that the human/mouse radiation chimera model may be of some value in the investigation of new vaccines, as an additional tool prior to clinical trials, and (iii) that the synthetic recombinant vaccine can induce a response in the human immune system and confers protection against influenza infection. Further investigation is needed to establish the efficacy of such a peptide vaccine in human subjects. (+info)
Augmentation of human influenza A virus-specific cytotoxic T lymphocyte memory by influenza vaccine and adjuvanted carriers (ISCOMS).
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There is a need to improve the ability of subunit vaccines to induce CD8(+) CTL responses in humans, especially for vaccines used to prevent illness by organisms that undergo antigenic variation at their major neutralizing antibody sites, e.g., influenza A viruses and human immunodeficiency virus. Murine models have demonstrated the protective role of cross-reactive CTL against influenza A virus antigenic drift. We tested the ability of an adjuvanted carrier (Iscomatrix) to help human antigen-presenting cells present formalin-killed influenza vaccine to human CD8(+) CTL clones in vitro and in vaccinated humans. The results of a randomized, double-blind, controlled clinical study demonstrate that a single dose of a vaccine formulated into Iscom particles increased influenza A virus-specific CTL memory in 50-60% of recipients, compared to 5% of the recipients of the standard influenza vaccine. (+info)
Safety and efficacy of intravenous zanamivir in preventing experimental human influenza A virus infection.
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Zanamivir is a potent inhibitor of influenza A and B virus neuraminidases and is active topically in experimental and natural human influenza. We conducted this double-blinded, placebo-controlled study to evaluate the safety and efficacy of intravenously administered zanamivir. Susceptible volunteers were randomized to receive either saline or zanamivir (600 mg) intravenously twice daily for 5 days beginning 4 h prior to intranasal inoculation with approximately 10(5) 50% tissue culture infectious doses (TCID50) of influenza A/Texas/36/91 (H1N1) virus. Reductions in the frequency of viral shedding (0% versus 100% in placebo, P < 0.005) and seroconversion (14% versus 100% in placebo, P < 0.005) and decreases in viral titer areas under the curve (0 versus 11.6 [median] log10 TCID50. day/ml in placebo, P < 0.005) were observed in the zanamivir group, as were reductions in fever (14% versus 88% in placebo, P < 0.05), upper respiratory tract illness (0% versus 100% in placebo, P < 0.005), total symptom scores (1 versus 44 [median] in placebo, P < 0.005), and nasal-discharge weight (3.9 g versus 17.5 g [median] in placebo, P < 0.005). Zanamivir was detectable in nasal lavage samples collected on days 2 and 4 (unadjusted median concentrations, 10.5 and 12.0 ng/ml of nasal wash, respectively). This study demonstrates that intravenously administered zanamivir is distributed to the respiratory mucosa and is protective against infection and illness following experimental human influenza A virus inoculation. (+info)
Importance of the carboxyl-terminal FTSL motif of membrane cofactor protein for basolateral sorting and endocytosis. Positive and negative modulation by signals inside and outside the cytoplasmic tail.
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Membrane cofactor protein (MCP), a widely distributed complement regulatory protein, is expressed on the basolateral surface of polarized epithelial cells, and it is not endocytosed. The carboxyl-terminal tetrapeptide (FTSL) is required for polarized surface expression. The ability of this tetrapeptide to serve as an autonomous sorting signal has been analyzed by adding this sequence motif to the C terminus of an apical membrane protein, the influenza A virus hemagglutinin (HA). The recombinant protein HA-FTSL retained the apical localization of the parental HA protein. Substitution of the complete cytoplasmic tail of MCP for the cytoplasmic tail of HA resulted in the targeting of the chimeric protein (HA/MCP) to the basolateral surface suggesting that the carboxyl-terminal FTSL motif is a weak sorting signal that requires additional targeting information from the membrane-proximal part of the cytoplasmic tail of MCP for redirecting an apical protein to the basolateral membrane domain. In contrast to the native HA, the HA-FTSL protein was subject to endocytosis. The basolateral HA/MCP was also found to be internalized and thus differed from the basolateral MCP. This result suggests that the carboxyl-terminal FTSL motif serves as an internalization signal and that in native MCP sorting information outside the cytoplasmic tail counteracts this endocytosis signal. Substitution of a tyrosine for the phenylalanine dramatically increased the internalization with most of the HA-YTSL protein being present intracellularly. Our results are consistent with the view that the interplay of multiple sorting signals and the modification of a well known targeting signal (YTSL) by amino acid exchange (FTSL) determine the constitutive expression of MCP on the basolateral surface of polarized epithelial cells. (+info)
The in situ spatial arrangement of the influenza A virus matrix protein M1 assessed by tritium bombardment.
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Intact influenza A virions were bombarded with thermally activated tritium atoms, and the intramolecular distribution of the label in the matrix protein M1 was analyzed to determine the in situ accessibility of its tryptic fragments. These data were combined with the previously reported x-ray crystal structure of the M1 fragment 2-158 [Sha, B. & Luo, M. (1997) Nat. Struct. Biol. 4, 239-244] and the predicted topology of the C domain (159-252) to propose a model of M1 arrangement in the virus particle. (+info)
Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections.
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The efficacy and safety of zanamivir, administered 2x or 4x daily over 5 days, was evaluated in the treatment of influenza infections. A total of 1256 patients entered the study; 57% of those randomized had laboratory-confirmed influenza infection. The primary end point, "alleviation of major symptoms," was created to evaluate differences in clinical impact. In the overall population with or without influenza infection, zanamivir reduced the median number of days to reach this end point by 1 day (P=.012 2x daily vs. placebo; P=.014 4x daily vs. placebo). The reduction was greater in patients treated within 30 h of symptom onset, febrile at study entry, and in defined high-risk groups. Zanamivir reduced nights of disturbed sleep, time to resumption of normal activities, and use of symptom relief medications. It was well tolerated. These results suggest that zanamivir can significantly reduce the duration and overall symptomatic effect of influenza. (+info)
Case-control study of risk factors for avian influenza A (H5N1) disease, Hong Kong, 1997.
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In May 1997, a 3-year-old boy in Hong Kong died of a respiratory illness related to influenza A (H5N1) virus infection, the first known human case of disease from this virus. An additional 17 cases followed in November and December. A case-control study of 15 of these patients hospitalized for influenza A (H5N1) disease was conducted using controls matched by age, sex, and neighborhood to determine risk factors for disease. Exposure to live poultry (by visiting either a retail poultry stall or a market selling live poultry) in the week before illness began was significantly associated with H5N1 disease (64% of cases vs. 29% of controls, odds ratio, 4.5, P=.045). By contrast, travel, eating or preparing poultry products, recent exposure to persons with respiratory illness, including persons with known influenza A (H5N1) infection, were not associated with H5N1 disease. (+info)