Role of innate lymphoid cells and dendritic cells in intradermal immunization of the enterovirus antigen

Abstract

Enterovirus type 71 (EV71) and coxsackievirus A 16 (CA16) are the major pathogens of human hand, foot, and mouth disease (HFMD). In our previous study, intramuscular immunization with the inactivated EV71 vaccine elicited effective immunity, while immunization with the inactivated CA16 vaccine did not. In this report, we focused on innate immune responses elicited by inactivated EV71 and CA16 antigens administered intradermally or intramuscularly. The distributions of the EV71 and CA16 antigens administered intradermally or intramuscularly were not obviously different, but the antigens were detected for a shorter period of time when administered intradermally. The expression levels of NF-κB pathway signaling molecules, which were identified as being capable of activating DCs, ILCs, and T cells, were higher in the intradermal group than in the intramuscular group. Antibodies for the EV71 and CA16 antigens colocalized with ILCs and DCs in skin and muscle tissues under fluorescence microscopy. Interestingly, ILC colocalization decreased over time, while DC colocalization increased over time. ELISpot analysis showed that coordination between DCs and ILCs contributed to successful adaptive immunity against vaccine antigens in the skin. EV71 and/or CA16 antigen immunization via the intradermal route was more capable of significantly increasing neutralizing antibody titers and activating specific T cell responses than immunization via the intramuscular route. Furthermore, neonatal mice born to mothers immunized with the EV71 and CA16 antigens were 100% protected against wild-type EV71 or CA16 viral challenge. Together, our results provide new insights into the development of vaccines for HFMD.

Enterovirus vaccine: Intradermal immunization improves protection

Coxsackievirus A 16 (CA16) and enterovirus 71 (EV71) infections are the most common cause of hand-foot-and-mouth diseases. Inactivated virus has been evaluated as potential vaccine for both viruses in animal models, but protection was only achieved for EV71. In this study, led by Qihan Li from the Chinese Academy of Medical Sciences, researchers show that intradermal, as compared to intramuscular immunization, results in an elevated immune response and improved protection from EV71 and CA16 infection in mice. Intradermal vaccination increases interaction of vaccine antigen with dendritic cells and innate lymphoid cells at the site of inoculation, as compared to intramuscular vaccination. Intradermal vaccination furthermore improves the antibody and T cell response and protects mice from infection. However, complete protection of mice from CA16 infection was only achieved after intradermal immunization with a combination of inactivated EV71 and CA16 vaccine, suggesting that further improvements of this vaccine candidate will be necessary.