Abstract

Three inactivated EV71 whole-virus vaccines have completed Phase III clinical trials in mainland China, with high efficacy, satisfactory safety, and sustained immunogenicity. However, the molecular mechanisms how this new vaccine elicit potent immune response remain poorly understood. To characterize the primary and recall responses to EV71 vaccines, PBMC from 19 recipients before and after vaccination with EV71 vaccine are collected and their gene expression signatures after stimulation with EV71 antigen were compared. The results showed that primary and recall response to EV71 antigen have both activated an IRF7 regulating type I interferon and antiviral immune response network. However, up-regulated genes involved in T cell activation regulated by IRF1, inflammatory response, B-cell activation and humoral immune response were only observed in recall response. The specific secretion of IL-10 in primary response and IL-2,IP-10,CCL14a, CCL21 in recall response was consistent with the activation of immune response process found in genes. Furthermore, the expression of MX1 and secretion of IP-10 in recall response were strongly correlated with NTAb level at 180d after vaccination (r = 0.81 and 0.99). In summary, inflammatory response, adaptive immune response and a stronger antiviral response were indentified in recall response.

Highlights

  • Hand foot and mouth disease (HFMD) is a serious public health problem in Western Pacific region countries[1]

  • Based on the epidemiological and clinical etiological data published in recent years, more than 80% of the pathogens isolated from patients died from HFMD were identified as enterovirus 71 (EV71)[3,4,5,6]

  • Our results provide a better understanding of the immune response induced by EV71 vaccine

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Summary

Introduction

Hand foot and mouth disease (HFMD) is a serious public health problem in Western Pacific region countries[1]. Three inactivated EV71 whole-virus vaccines in mainland China have completed Phase III clinical trials in more than 30,000 infants and children Results showed that these vaccines were safe and there were over 90% efficacy in preventing EV71-associated HFMD, 80% efficacy in preventing EV71-associated diseases[7,8,9]. Systems biology approach has been used to predict the development of protective immunity after vaccination by profiling gene expression of PBMC samples from vaccinated individuals. This approach has been pioneered in the studies of yellow fever vaccine[10,11], influenza vaccine[12] and HPV virus-like particles vaccine[13]. Our results provide a better understanding of the immune response induced by EV71 vaccine

Study design
Inactivated EV71 whole-virus vaccine and EV71 liquid bulk
PBMCs incubation and RNA extraction
Microarray analysis
Quantitative real-time PCR and confirmation of microarray results
Protein array analysis
Neutralizing Antibody
The neutralizing antibodies response to EV71 vaccine
Confirmation of a subset of DEGs by quantitative RT-PCR
Cytokine secretion profiles in primary and recall immune response
Discussion

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