Dataset Information

Genetic and antigenic analysis of the first A/New Caledonia/20/99-like H1N1 influenza isolates reported in the Americas.

ABSTRACT: From February through May of 1999, 13 cases of Influenza A virus (FLUAV), type H1N1 were reported at a Department of Defense influenza surveillance sentinel site in Lima, Peru. Genetic and antigenic analysis by hemagglutination inhibition and direct nucleotide sequencing of the HA1 region of the hemagglutinin gene were performed on two isolates, A/Peru/1641/99 and A/Peru/1798/99. Both isolates were distinct from the Bayern/7/95-like viruses circulating in the Americas and closely related to a Beijing/262/95-like variant, A/New Caledonia/20/99. With the exception of travel-related cases, the detection of these isolates represents the first appearance of New Caledonia/20/99-like viruses in the Americas. Since the characterization of these Peru isolates, a number of New Caledonia/20/99-like viruses have been reported worldwide. For the 2000/01 and 2001/02 influenza seasons, the World Health Organization (WHO) has recommended the inclusion of A/New Caledonia/20/99 as the H1N1 vaccine component for both the southern and northern hemispheres.

SUBMITTER: Daum LT

PROVIDER: S-EPMC2730241 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature

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Genetic and antigenic analysis of the first A/New Caledonia/20/99-like H1N1 influenza isolates reported in the Americas.

Daum Luke T LT Canas Linda C LC Smith Catherine B CB Klimov Alexander A Huff William W Barnes William W Lohman Kenton L KL

Emerging infectious diseases 20020401 4

From February through May of 1999, 13 cases of Influenza A virus (FLUAV), type H1N1 were reported at a Department of Defense influenza surveillance sentinel site in Lima, Peru. Genetic and antigenic analysis by hemagglutination inhibition and direct nucleotide sequencing of the HA1 region of the hemagglutinin gene were performed on two isolates, A/Peru/1641/99 and A/Peru/1798/99. Both isolates were distinct from the Bayern/7/95-like viruses circulating in the Americas and closely related to a Be ...[more]

PMID: 11971776

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Project description:Genome-wide gene expression patterns were measured in human monocyte-derived dendritic cells (DCs) infected in vitro with seasonal H1N1 influenza A/New Caledonia/20/1999. To provide a mechanistic explanation for the timing of gene expression changes over the first 12 hours post-infection, we developed a statistically rigorous enrichment approach integrating genome-wide expression kinetics and time-dependent promoter analysis. Our approach, TI me-Dependent Activity Linker (TIDAL), generates a regulatory network that connects transcription factors associated with each temporal phase of the response into a coherent linked cascade. TIDAL infers 12 transcription factors and 32 regulatory connections that drive the antiviral response to influenza. To demonstrate the generality of this approach, TIDAL was also used to generate a network for the DC response to measles infection. Monocyte-derived DCs were obtained from healthy human blood donors following a standard protocol. The recent seasonal H1N1 influenza virus A/New Caledonia/20/1999 (NC) virus was titrated by immunofluorescence 18 hours after infection of MDCK cell plates using monoclonal antibodies specific for Influenza-NP protein generated by the Mount Sinai Hybridoma Core Facility followed by addition of anti-mouse IgG-FITC and visualization using fluorescent microscopy. For infection of naive DCs, NC stocks were appropriately diluted in DulbeccoM-bM-^@M-^Ys Modified Eagle Medium (DMEM) and added directly into pelleted DCs at a multiplicity of infection (MOI) of 1 After incubation for 40 minutes at 37 M-bM-^WM-&C, fresh DC growth medium (without GMCSF and IL-4) was added back to the infected cells (1 106 cells/ml) for the remainder of the infection. The reaction was stopped at 1, 2, 4, 6, 8, 10, and 12 hours after infection by fixing the cells with RNAprotect Cell Reagent (Qiagen, Duesseldorf Germany). Naive non-infected DCs underwent the same experimental procedure as infected DCs in the absence of virus to ensure that mechanical manipulations could not be responsible for differences in experimental readouts. All time points and controls were performed in triplicates. Cells were homogenized by using QIAshredder microcentrifuge spin-columns (Qiagen, Duesseldorf Germany) and RNA was isolated from cells using Qiagen Micro RNeasy plus kit following the manufactures protocol (Qiagen, Duesseldorf Germany). RNA quality was assayed by determination of the RNA integrity number using the 2100 Bioanalyzer (Agilent). RNA samples were processed and hybridized to HumanHT-12 v4 Expression BeadChip Kit (Illumina San Diego, CA) by the Mount Sinai Genomics Institute following the manufacturerM-bM-^@M-^Ys instructions, and raw expression data were output by the Illumina GenomeStudio software.

Project description:The ease at which influenza virus sequence data can be used to estimate antigenic relationships between strains and the existence of databases containing sequence data for hundreds of thousands influenza strains make sequence-based antigenic distance estimates an attractive approach to researchers. Antigenic mismatch between circulating strains and vaccine strains results in significantly decreased vaccine effectiveness. Furthermore, antigenic relatedness between the vaccine strain and the strains an individual was originally primed with can affect the cross-reactivity of the antibody response. Thus, understanding the antigenic relationships between influenza viruses that have circulated is important to both vaccinologists and immunologists.Here we develop a method of mapping antigenic relationships between influenza virus stains using a sequence-based antigenic distance approach (SBM). We used a modified version of the p-all-epitope sequence-based antigenic distance calculation, which determines the antigenic relatedness between strains using influenza hemagglutinin (HA) genetic coding sequence data and provide experimental validation of the p-all-epitope calculation. We calculated the antigenic distance between 4838 H1N1 viruses isolated from infected humans between 1918 and 2016. We demonstrate, for the first time, that sequence-based antigenic distances of H1N1 Influenza viruses can be accurately represented in 2-dimenstional antigenic cartography using classic multidimensional scaling. Additionally, the model correctly predicted decreases in cross-reactive antibody levels with 87% accuracy and was highly reproducible with even when small numbers of sequences were used.This work provides a highly accurate and precise bioinformatics tool that can be used to assess immune risk as well as design optimized vaccination strategies. SBM accurately estimated the antigenic relationship between strains using HA sequence data. Antigenic maps of H1N1 virus strains reveal that strains cluster antigenically similar to what has been reported for H3N2 viruses. Furthermore, we demonstrated that genetic variation differs across antigenic sites and discuss the implications.

Project description:BackgroundThere has been considerable uptake of seasonal influenza vaccines in the Americas compared to other regions. We describe the current influenza vaccination target groups, recent progress in vaccine uptake and in generating evidence on influenza seasonality and vaccine effectiveness for immunization programs. We also discuss persistent challenges, 5 years after the A(H1N1) 2009 influenza pandemic.MethodsWe compiled and summarized data annually reported by countries to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF joint report form on immunization, information obtained through PAHO's Revolving Fund for Vaccine Procurement and communications with managers of national Expanded Programs on Immunization (EPI).ResultsSince 2008, 25 countries/territories in the Americas have introduced new target groups for vaccination or expanded the age ranges of existing target groups. As of 2014, 40 (89%) out of 45 countries/territories have policies established for seasonal influenza vaccination. Currently, 29 (64%) countries/territories target pregnant women for vaccination, the highest priority group according to WHO´s Stategic Advisory Group of Experts and PAHO/WHO's Technical Advisory Group on Vaccine-preventable Diseases, compared to only 7 (16%) in 2008. Among 23 countries reporting coverage data, on average, 75% of adults ?60 years, 45% of children aged 6-23 months, 32% of children aged 5-2 years, 59% of pregnant women, 78% of healthcare workers, and 90% of individuals with chronic conditions were vaccinated during the 2013-14 Northern Hemisphere or 2014 Southern Hemisphere influenza vaccination activities. Difficulties however persist in the estimation of vaccination coverage, especially for pregnant women and persons with chronic conditions. Since 2007, 6 tropical countries have changed their vaccine formulation from the Northern to the Southern Hemisphere formulation and the timing of their campaigns to April-May following the review of national evidence. LAC countries have also established an official network dedicated to evaluating influenza vaccines effectiveness and impact.ConclusionFollowing the A(H1N1)2009 influenza pandemic, countries of the Americas have continued their efforts to sustain or increase seasonal influenza vaccine uptake among high risk groups, especially among pregnant women. Countries also continued strengthening influenza surveillance, immunization platforms and information systems, indirectly improving preparedness for future pandemics. Influenza vaccination is particularly challenging compared to other vaccines included in EPI schedules, due to the need for annual, optimally timed vaccination, the wide spectrum of target groups, and the limitations of the available vaccines. Countries should continue to monitor influenza vaccination coverage, generate evidence for vaccination programs and implement social communication strategies addressing existing gaps.

Dataset Information

Genetic and antigenic analysis of the first A/New Caledonia/20/99-like H1N1 influenza isolates reported in the Americas.

Publications

Genetic and antigenic analysis of the first A/New Caledonia/20/99-like H1N1 influenza isolates reported in the Americas.

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