Dataset Information

Neutralization of Enterovirus D68 isolated from the 2014 US outbreak by commercial intravenous immune globulin products.

ABSTRACT: BACKGROUND:In 2014, an outbreak of Enterovirus D68 (EV-D68) was recorded as the largest in the US with cases confirmed in 49 states. Intravenous immune globulin (IVIG) has been used to treat enterovirus infections in neonates and is an accepted replacement therapy for immunodeficient patients. OBJECTIVES:This study aimed to detect the presence of neutralizing antibodies to EV-D68 viruses from the 2014 outbreak in commercially available IVIG products. STUDY DESIGN:Commercially available lots of IVIG preparations were obtained from five different manufacturers (2-10 preparations per manufacturer) and tested for neutralizing antibodies against the prototype EV-D68 virus and three EV-D68 isolates representing strains circulating during the 2014 outbreak. RESULTS:All lots of IVIG tested were positive for EV-D68 neutralizing antibodies, with high titers ranging from 9.5log2 to 17.5log2, and with comparable median titers to all four EV-D68 viruses. CONCLUSIONS AND DISCUSSION:Amino acid sequence differences in the regions of the predicted antigenic sites on the viral capsid may explain some of the differences in neutralization among the different strains. The neutralization titers suggests that the 2014 outbreak EV-D68 viruses share some antigenic sites with the prototype virus and also present some unique antigenic sites distinct from the prototype. However, the commercial IVIG lots tested all contained high levels of neutralizing antibodies against EV-D68.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC6512324 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Neutralization of Enterovirus D68 isolated from the 2014 US outbreak by commercial intravenous immune globulin products.

Zhang Yiting Y Moore Deborah D DD Nix W Allan WA Oberste M Steven MS Weldon William C WC

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 20150619

<h4>Background</h4>In 2014, an outbreak of Enterovirus D68 (EV-D68) was recorded as the largest in the US with cases confirmed in 49 states. Intravenous immune globulin (IVIG) has been used to treat enterovirus infections in neonates and is an accepted replacement therapy for immunodeficient patients.<h4>Objectives</h4>This study aimed to detect the presence of neutralizing antibodies to EV-D68 viruses from the 2014 outbreak in commercially available IVIG products.<h4>Study design</h4>Commercial ...[more]

PMID: 26209401

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Project description:UnlabelledIn August 2014, an outbreak of enterovirus D68 (EV-D68) occurred in North America, causing severe respiratory disease in children. Due to a lack of complete genome sequence data, there is only a limited understanding of the molecular evolution and epidemiology of EV-D68 during this outbreak, and it is uncertain whether the differing clinical manifestations of EV-D68 infection are associated with specific viral lineages. We developed a high-throughput complete genome sequencing pipeline for EV-D68 that produced a total of 59 complete genomes from respiratory samples with a 95% success rate, including 57 genomes from Kansas City, MO, collected during the 2014 outbreak. With these data in hand, we performed phylogenetic analyses of complete genome and VP1 capsid protein sequences. Notably, we observed considerable genetic diversity among EV-D68 isolates in Kansas City, manifest as phylogenetically distinct lineages, indicative of multiple introductions of this virus into the city. In addition, we identified an intersubclade recombination event within EV-D68, the first recombinant in this virus reported to date. Finally, we found no significant association between EV-D68 genetic variation, either lineages or individual mutations, and a variety of demographic and clinical variables, suggesting that host factors likely play a major role in determining disease severity. Overall, our study revealed the complex pattern of viral evolution within a single geographic locality during a single outbreak, which has implications for the design of effective intervention and prevention strategies.ImportanceUntil recently, EV-D68 was considered to be an uncommon human pathogen, associated with mild respiratory illness. However, in 2014 EV-D68 was responsible for more than 1,000 disease cases in North America, including severe respiratory illness in children and acute flaccid myelitis, raising concerns about its potential impact on public health. Despite the emergence of EV-D68, a lack of full-length genome sequences means that little is known about the molecular evolution of this virus within a single geographic locality during a single outbreak. Here, we doubled the number of publicly available complete genome sequences of EV-D68 by performing high-throughput next-generation sequencing, characterized the evolutionary history of this outbreak in detail, identified a recombination event, and investigated whether there was any correlation between the demographic and clinical characteristics of the patients and the viral variant that infected them. Overall, these results will help inform the design of intervention strategies for EV-D68.

Dataset Information

Neutralization of Enterovirus D68 isolated from the 2014 US outbreak by commercial intravenous immune globulin products.

Publications

Neutralization of Enterovirus D68 isolated from the 2014 US outbreak by commercial intravenous immune globulin products.

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