Abstract
The emerging human enterovirus 71 (EV71) represents a growing threat to public health, and no vaccine or specific antiviral is currently available. Human intravenous immunoglobulin (IVIG) is clinical used in treating severe EV71 infections. However, the discovery of antibody dependent enhancement (ADE) of EV71 infection illustrates the complex roles of antibody in controlling EV71 infection. In this study, to identify the distinct role of each IgG subclass on neutralization and enhancement of EV71 infection, different lots of pharmaceutical IVIG preparations manufactured from Chinese donors were used for IgG subclass fractionation by pH gradient elution with the protein A-conjugated affinity column. The neutralization and ADE capacities on EV71 infection of each purified IgG subclass were then assayed, respectively. The neutralizing activity of human IVIG is mainly mediated by IgG1 subclass and to less extent by IgG2 subclass. Interestingly, IgG3 fraction did not have neutralizing activity but enhanced EV71 infection in vitro. These results revealed the different roles of human IgG subclasses on EV71 infection, which is of critical importance for the rational design of immunotherapy and vaccines against severe EV71 diseases.
Highlights
Human enterovirus type 71 (EV71), a member of the genus Enterovirus family Picornaviridae, is a typical positive-sense singlestranded RNA virus
Different lots of commercial human intravenous immunoglobulin (IVIG) products manufactured from pooled plasma units from healthy Chinese donors were used to fractionate each IgG subclass by pH gradient elution with the protein A-conjugated affinity column
The distribution and purity of each IgG subclass were shown in Table 1, and only minor variation were observed among different lots of IVIG preparations
Summary
Human enterovirus type 71 (EV71), a member of the genus Enterovirus family Picornaviridae, is a typical positive-sense singlestranded RNA virus. EV71 was first isolated from an infant with encephalitis in California, USA in 1969 [2], and associated with mild diseases and sporadical epidemic globally in the following thirty years. Large outbreaks of EV71 infections with severe neurological complications have been reported in Bulgaria, Hungary, Sarawak, Vietnam, Malaysia, Singapore, Korea, Taiwan and Japan [3]. In Asia-Pacific countries, EV71 has emerged as the leading cause of viral encephalitis in infants and young children. Since 2008, millions of EV71 infection cases including thousands of deaths have been reported in mainland China [4,5]. Considering its global distribution, rapid evolution and neurological tropism [3], EV71 has been recognized as a critical emerging threat to global public health. There is no vaccine or specific antiviral drugs currently available for EV71 infection
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