T Cell Immunity To Enterovirus 71 Infection In Humans And Implications For Vaccine Development

Abstract

Enterovirus 71 (EV-A71) is one of the major pathogens causing hand, foot and mouth disease (HFMD). Some strains can lead to neurological disease and fatality in children. Up to date, there is no FDA-approved vaccine to prevent severe HFMD and mortality. Although the inactivated vaccine has advanced to production in China, lack of long-term protection and the requirement of multiple boosters have necessitated the development of other types of vaccines. Recent studies indicate that cellular and not humoral immunity determines the clinical outcome of EV-A71 infections. High levels of cytokines such as IL-1β, IL-6, IL-10 and IFN-γ tend to correlate with clinical severity in patients with pulmonary edema and encephalitis. The live attenuated vaccine may serve as the preferred choice as it can induce excellent humoral and cellular immunity as well as live-long immunity. Expression of certain HLA alleles such as TNF-α promoter type II (-308 allele), HLA-A33 and HLA-DR17 responses have been linked to severe HFMD. However, the high variability of MHC genes could restrict T cell recognition and be a major obstacle in the design of peptide vaccines. Hence, the development of a T cell universal vaccine (incorporating both CD4+ and CD8+ T cell epitopes) that induces broad, multifunctional and cross-reactive CD8+ T cell responses maybe desirable.

Host–virus interaction and viral evasion

“…Viruses encode proteins that may interfere with the expression of MHC class II antigens by negatively regulating their transcription and/or disrupting their normal cell trafficking, interfering with their presentation to naive CD4+ T cells by disrupting the interaction between MHC class II antigens and TCRs. This is what occurs with the human immunodeficiency virus (HIV) proteins Tat and Nef, as described in more detail throughout this review (Cao et al, 2018; Rivino, 2018; Yee & Poh, 2018).…”

A practical method for evaluating thein vivoefficacy of EVA-71 vaccine using a hSCARB2 knock-in mouse model

“…challenge groups ( Figure 6 ). It has been reported that high levels of cytokines such as IL-1β, IL-6, IL-10, and IFN-γ are correlated with clinical severity in patients with pulmonary oedema and encephalitis [ 52 , 53 ], indicating that the immune response of the hSCARB2 mouse model was similar to that of humans. Vaccination prevented the increase in the expression of these cytokines, keeping them at normal levels, indicating that these cytokine responses might be directly related to vaccine-induced immunity.…”

From Monovalent to Multivalent Vaccines, the Exploration for Potential Preventive Strategies Against Hand, Foot, and Mouth Disease (HFMD)

“…(3) Genetic variations. There may be intrinsic differences between individuals in countering a viral invasion due to inherited variations in host factors that determine viral susceptibility at the cellular and organismal levels (Yee and Poh 2018).…”

“…(3) Genetic variations. There may be intrinsic differences between individuals in countering a viral invasion due to inherited variations in host factors that determine viral susceptibility at the cellular and organismal levels (Yee and Poh 2018 ). Among the three abovementioned factors, the cellular immune response is the most feasible target for vaccine-based prevention.…”