Dataset Information

Non-neutralizing Antibody Responses against VP1 in Enterovirus A, B, C and Rhinovirus A species among Infants and Children in Shanghai.

ABSTRACT: The overall non-neutralizing antibody responses against EV infections among infants and children remain unknown. The non-neutralizing antibody responses against VP1 of EV-A species (Enterovirus 71 (EV71), Coxsackievirus A16 (CA16)), EV-B species (Coxsackievirus B3 (CB3)), EV-C species (Poliovirus 1 (PV1)) and RV-A species (Rhinovirus A N13 (RV13)) were detected and analyzed using a novel evolved immunoglobulin-binding molecule (NEIBM)-based ELISA among infants and children aged 1?day to 6 years in Shanghai. The anti-VP1 reactivity against these EVs changed similarly in an age-related dynamic: being high level in the 1-28-day age group, declining to the lowest level in the 1-12-month age group, gradually increasing to the peak level in the 13-60-month age group, and remarkably declining in the 61-72-month age group, which reflects the conversion from maternally-derived to primary antibody responses. The anti-RV13 VP1 antibodies were demonstrated at the highest level, with anti-CB3 and PV1 VP1 antibodies at the second highest level and anti-CA16 and EV71 VP1 antibodies at the lowest level. These findings are the first to describe the overall non-neutralizing antibody responses against VP1 of the EV-A, B, C and RV-A viruses among the infants and children and could be helpful for further understanding the ubiquitous EV infections among children.

SUBMITTER: Ding Y

PROVIDER: S-EPMC5882884 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Non-neutralizing Antibody Responses against VP1 in Enterovirus A, B, C and Rhinovirus A species among Infants and Children in Shanghai.

Ding Yingying Y Rui Bing B Gao Caixia C Xu Menghua M Wang Lili L Zhao Chunyan C Bai Jie J Wang Jinhong J Xu Jin J Pan Wei W

Scientific reports 20180403 1

The overall non-neutralizing antibody responses against EV infections among infants and children remain unknown. The non-neutralizing antibody responses against VP1 of EV-A species (Enterovirus 71 (EV71), Coxsackievirus A16 (CA16)), EV-B species (Coxsackievirus B3 (CB3)), EV-C species (Poliovirus 1 (PV1)) and RV-A species (Rhinovirus A N13 (RV13)) were detected and analyzed using a novel evolved immunoglobulin-binding molecule (NEIBM)-based ELISA among infants and children aged 1 day to 6 years ...[more]

PMID: 29615683

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Project description:Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and sometimes causes severe or fatal neurological complications. The amino acid at VP1-145 determines virological characteristics of EV71. Viruses with glutamic acid (E) at VP1-145 (VP1-145E) are virulent in neonatal mice and transgenic mice expressing human scavenger receptor B2, whereas those with glutamine (Q) or glycine (G) are not. However, the contribution of this variation to pathogenesis in humans is not fully understood. We compared the virulence of VP1-145E and VP1-145G viruses of Isehara and C7/Osaka backgrounds in cynomolgus monkeys. VP1-145E, but not VP1-145G, viruses induced neurological symptoms. VP1-145E viruses were frequently detected in the tissues of infected monkeys. VP1-145G viruses were detected less frequently and disappeared quickly. Instead, mutants that had a G to E mutation at VP1-145 emerged, suggesting that VP1-145E viruses have a replication advantage in the monkeys. This is consistent with our hypothesis proposed in the accompanying paper that the VP1-145G virus is attenuated due to its adsorption by heparan sulfate. Monkeys infected with both viruses produced neutralizing antibodies before the onset of the disease. Interestingly, VP1-145E viruses were more resistant to neutralizing antibodies than VP1-145G viruses in vitro A small amount of neutralizing antibody raised in the early phase of infection may not be sufficient to block the dissemination of VP1-145E viruses. The different resistance of the VP1-145 variants to neutralizing antibodies may be one of the reasons for the difference in virulence.IMPORTANCE The contribution of VP1-145 variants in humans is not fully understood. In some reports, VP1-145G/Q viruses were more frequently isolated from severely affected than from mildly affected patients, suggesting that VP1-145G/Q viruses are more virulent. In the accompanying paper, we showed that VP1-145E viruses are more virulent than VP1-145G viruses in human SCARB2 transgenic mice. Heparan sulfate acts as a decoy to specifically trap the VP1-145G viruses and leads to abortive infection. Here, we demonstrated that VP1-145G was attenuated in cynomolgus monkeys, suggesting that this hypothesis is also true in a non-human primate model. VP1-145E viruses, but not VP1-145G viruses, were highly resistant to neutralizing antibodies. We propose the difference in resistance against neutralizing antibodies as another mechanism of EV71 virulence. In summary, VP1-145 contributes to virulence determination by controlling attachment receptor usage and antibody sensitivity.

Project description:EV71 is one of major etiologic causes of hand-foot-mouth disease (HFMD) and leads to severe neurological complications in young children and infants. Recently inactivated EV71 vaccines have been developed by five manufactures and clinically show good safety and immunogenicity. However, the cross-neutralizing activity of these vaccines remains unclear, and is of particular interest because RNA recombination is seen more frequently in EV71 epidemics.In this post-hoc study, sera from a subset of 119 infants and children in two clinical trials of EV71 subgenotype C4 vaccines (ClinicalTrials.gov Identifier: NCT01313715 and NCT01273246), were detected for neutralizing antibody (NTAb) titres with sera from infected patients as controls. Cytopathogenic effect method was employed to test NTAb against EV71 subgenotype B4, B5, C2, C4 and C5, which were prominent epidemic strains worldwide over the past decade. To validate the accuracy of the results, ELISpot assay was employed in parallel to detect NTAb in all the post-vaccine sera. After two-dose vaccination, 49 out of 53 participants in initially seronegative group and 52 out of 53 participants in initially seropositive group showed less than 4-fold differences in NTAb titers against five EV71 strains, whereas corresponding values among sera from pediatric patients recovering from EV71-induced HFMD and subclinically infected participants were 8/8 and 41/43, respectively. The geometric mean titers of participants against five subgenotypes EV71 all grew significantly after vaccinations, irrespective of the baseline NTAb titer. The relative fold increase in antibody titers (NTAb-FI) against B4, B5, C2, and C5 displayed a positive correlation to the NTAb-FI against C4.The results demonstrated broad cross-neutralizing activity induced by two C4 EV71 vaccines in healthy Chinese infants and children. However, the degree of induced cross-protective immunity, and the potential escape evolution for EV71 still need to be monitored and researched in future for these new vaccines.

Dataset Information

Non-neutralizing Antibody Responses against VP1 in Enterovirus A, B, C and Rhinovirus A species among Infants and Children in Shanghai.

Publications

Non-neutralizing Antibody Responses against VP1 in Enterovirus A, B, C and Rhinovirus A species among Infants and Children in Shanghai.

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