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1.
Proc Natl Acad Sci U S A ; 107(44): 18979-84, 2010 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-20956293

RESUMO

Current influenza virus vaccines protect mostly against homologous virus strains; thus, regular immunization with updated vaccine formulations is necessary to guard against the virus' hallmark remodeling of regions that mediate neutralization. Development of a broadly protective influenza vaccine would mark a significant advance in human infectious diseases research. Antibodies with broad neutralizing activity (nAbs) against multiple influenza virus strains or subtypes have been reported to bind the stalk of the viral hemagglutinin, suggesting that a vaccine based on this region could elicit a broadly protective immune response. Here we describe a hemagglutinin subunit 2 protein (HA2)-based synthetic peptide vaccine that provides protection in mice against influenza viruses of the structurally divergent subtypes H3N2, H1N1, and H5N1. The immunogen is based on the binding site of the recently described nAb 12D1, which neutralizes H3 subtype viruses, demonstrates protective activity in vivo, and, in contrast to a majority of described nAbs, appears to bind to residues within a single α-helical portion of the HA2 protein. Our data further demonstrate that the specific design of our immunogen is integral in the induction of broadly active anti-hemagglutinin antibodies. These results provide proof of concept for an HA2-based influenza vaccine that could diminish the threat of pandemic influenza disease and generally reduce the significance of influenza viruses as human pathogens.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Hemaglutininas Virais/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Infecções por Orthomyxoviridae/imunologia , Peptídeos/imunologia , Animais , Hemaglutininas Virais/farmacologia , Humanos , Imunização , Vacinas contra Influenza/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/prevenção & controle , Peptídeos/farmacologia , Estrutura Secundária de Proteína
2.
Environ Toxicol Chem ; 31(6): 1223-30, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22447337

RESUMO

The authors compared blood plasma concentrations of 13 perfluoroalkyl contaminants (PFCs) in five sea turtle species with differing trophic levels. Wild sea turtles were blood sampled from the southeastern region of the United States, and plasma was analyzed using liquid chromatography tandem mass spectrometry. Mean concentrations of perfluorooctane sulfonate (PFOS), the predominant PFC, increased with trophic level from herbivorous greens (2.41 ng/g), jellyfish-eating leatherbacks (3.95 ng/g), omnivorous loggerheads (6.47 ng/g), to crab-eating Kemp's ridleys (15.7 ng/g). However, spongivorous hawksbills had surprisingly high concentrations of PFOS (11.9 ng/g) and other PFCs based on their trophic level. These baseline concentrations of biomagnifying PFCs demonstrate interesting species and geographical differences. The measured PFOS concentrations were compared with concentrations known to cause toxic effects in laboratory animals, and estimated margins of safety (EMOS) were calculated. Small EMOS (<100), suggestive of potential risk of adverse health effects, were observed for all five sea turtle species for immunosuppression. Estimated margins of safety less than 100 were also observed for liver, thyroid, and neurobehavorial effects for the more highly exposed species. These baseline concentrations and the preliminary EMOS exercise provide a better understanding of the potential health risks of PFCs for conservation managers to protect these threatened and endangered species.


Assuntos
Monitoramento Ambiental , Fluorocarbonos/sangue , Tartarugas/sangue , Poluentes Químicos da Água/sangue , Ácidos Alcanossulfônicos/análise , Ácidos Alcanossulfônicos/sangue , Animais , Espécies em Perigo de Extinção , Feminino , Fluorocarbonos/análise , Estados Unidos , Poluentes Químicos da Água/análise
3.
Environ Sci Technol ; 44(13): 5202-9, 2010 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-20521819

RESUMO

Perfluorinated compounds (PFCs) are globally distributed persistent environmental contaminants. This study provides temporal trends as well as large-scale spatial trends of PFC concentrations in threatened juvenile loggerhead sea turtles near or from Florida Bay (FL Bay), Cape Canaveral (FL), Charleston (SC), Core Sound (NC), and Chesapeake Bay (MD). PFCs were extracted from 163 plasma and serum samples using solid-phase extraction and quantified with LC-MS/MS. Concentrations of six compounds significantly varied by site, with MD or FL Bay turtles having the highest concentrations. Perfluorooctane sulfonate (PFOS) was the predominant PFC at all sites (range: 0.31 ng/g to 39.0 ng/g). FL Bay turtles, compared to other sites, accumulated a unique PFC pattern with a higher proportion of perfluorocarboxylates compared to PFOS. Furthermore, this study was the first to statistically correlate wildlife PFC concentrations with human population, used as a proxy for urbanization and sources of PFCs to the environment. Positive relationships were found in which human population accounted for 75 and 81% of the variance in turtle PFOS and perfluoroundecanoate (PFUnA) concentrations (p = 0.06 and 0.04), respectively. PFOS and perfluorononanoate (PFNA) significantly decreased from 2000-2008 in SC turtles annually by 20 and 11%, respectively (p

Assuntos
Compostos de Flúor/análise , Tartarugas/metabolismo , Animais , Calibragem , Espécies em Perigo de Extinção , Monitoramento Ambiental/métodos , Florida , Geografia , Humanos , Maryland , North Carolina , Análise de Regressão , South Carolina , Fatores de Tempo , Estados Unidos
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