Insights into innate and adaptive immune responses in vaccine development against EV-A71

Abstract

Enterovirus A71 (EV-A71) is one of the major causative agents of hand, foot and mouth disease (HFMD) in the world, infecting mostly infants and young children (<5 years of age) in Asia. Approximately 2 million cases of HFMD were reported in China each year, of which approximately 45–50% were due to EV-A71. Most of the HFMD infections caused by EV-A71 usually result in mild symptoms with rashes and ulcers in the mouth. However, virulent strains of EV-A71 can infect the central nervous system and cause severe neurologic diseases, leading to reduced cognitive ability, acute flaccid paralysis and death. The lack of understanding of cellular immunity for long-term protection from the HFMD disease represents a major obstacle for vaccine development. In particular, the role of innate and T cell immunity during HFMD infection remains unclear and there is evidence suggesting the importance of CD4+ and CD8+ T cells for protective immunity. Currently, no US FDA-approved vaccine is available for EV-A71. Although the inactivated vaccines produced in China are highly effective (vaccine efficacy >95%), they lack the cellular immunity required for long-term protection. In this review, we discuss the findings that support the protective roles of innate and T cell immunity against EV-A71 infection, which will provide the knowledge needed for the urgent development of efficacious vaccines that will confer long-term protection.

Insight into the Enterovirus A71: A review

“…The inactivated vaccines are generally less immunogenic than the live attenuated vaccines, because the former are unable to replicate. 174 Live attenuated vaccine (LAV) is generated by reducing the virulence of a virus to the level of being harmless but retaining its antigenicity and ability to replicate. The advantages of LAV include elicitation of longer-lasting immunity and more costeffective production.…”

“…In addition, LAV cannot be administered to immunocompromised individuals. 174,175 The potential for developing a LAV for EV-A71 has been explored. An example, live attenuated EV-A71 vaccine strains that confer protection against lethal challenge in mice have been created using the more recent microRNA-based approach.…”

Economic Evaluation of Vaccines: Belgian Reflections on the Need for a Broader Perspective

“…Direct nonspecific benefits can be caused by heterologous immune stimulation from vaccination, promoting the overall immune system by inducing trained-innate immune memory. [29][30][31][32][33][34][35] Indirect nonspecific benefits result from vaccine-mediated depletion of a vaccine-target pathogen with associated short-or long-term immunosuppressive effect. 36 Table 1.…”

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

“…Humoral immune responses against HFMD-related viruses produce virus-specific neutralizing antibodies, which are generally sufficient to curb virus spreading and makes HFMD a self-limiting disease. However, there were reported cases in infants and young children where severe complications developed despite normal or nearly normal antibody titers compared to patients with mild HFMD, which indicates that other factors contribute to the disease severity (Lim and Poh 2019 ). The following factors may influence severity: (1) Variation in the IgG composition.…”