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. 2015 Aug:69:172-5.
doi: 10.1016/j.jcv.2015.06.086. Epub 2015 Jun 19.

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

Yiting Zhang  1 , Deborah D Moore  1 , W Allan Nix  1 , M Steven Oberste  1 , William C Weldon  2
Affiliations

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

Yiting Zhang et al. J Clin Virol. 2015 Aug.

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.

Keywords: Antibody titers; Enterovirus D68; Intravenous immunoglobulin.

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Conflict of interest statement

Conflict of Interest

None to declare.

Figures

Figure 1
Figure 1
Enterovirus D68 (EV-D68) antisera recognizes homologous EV-D68 virus and 2014 outbreak strains. Antisera raised against the Fermon strain and EV-D70 were used to determine the specificity of the serology assay. Median titers are shown for three replicate assay runs. ULD = upper limit of detection, LLD = lower limit of detection; * p > 0.05 for difference in median titers, with Fermon as the reference.
Figure 2
Figure 2
Commercial IVIG lots neutralize EV-D68 strains with equivalent efficiencies. IVIG products were tested for neutralizing antibodies against the EV-D68 strains Fermon (A) and three clinical isolates 14–18949 (B), 14–18952 (C), and 14–18953 (D). For each manufacturer, median neutralization titers are indicated in box plots with horizontal line with 5–95% confidence intervals. (A, n=10; B, n=10; C, n=3; D, n=4, E, n=2). Data represents results from a single assay run. *p < 0.05, ** p < 0.01, *** p < 0.001 for difference in median titers.
Figure 3
Figure 3
Protein sequence alignment of putative antigenic sites for EV-D68 viruses used in microneutralization assay. Alignments of EV-D68 capsid proteins VP1 (A), VP2 (B), and VP3 (C); only amino acid residues that differ from Fermon virus are shown. Residue number for each amino acid chain is based on the predicted cleavage sites from Liu et al [8]. Putative antigenic sites based on RV-14 are shaded as follows: NIm-IA (orange), Nim-IB (blue), Nim-II (green), and Nim-III (yellow). * denotes an amino acid deletion at residue 140 in 14–18953. - denotes a gap in the sequence alignment due to a two-amino-acid insertion in 14–18953.
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References

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