Natural killer T cells play a significant role in preventing Coxsackievirus A10 infection through an adeno-based vaccine expressing enterovirus-like particles

We study a potent valent vaccine based on adenovector expressing enterovirus A71 (EV-A71) viral like particle (AdVLP) which elicits a multivalence against not only EV-A71 but also other coxsackieviruses such as A10. In young-aged human scavenger receptor class B, member 2 -transgenic ((hSCARB2-Tg) mice received two-dose of vaccine following challenge with CVA10, AdVLP immunization significantly reduced muscle, spinal cord, and brain's viral amounts and protected animal from disease occurrence. In contrast, massive CVA10 accumulated in these tissues that resulted in severe diseases and death in the control vector-received mice. Passive immunization of Tg mice with serum from AdVLP-immunized subjects, following challenge with CVA10, demonstrated that the antibodies in the serum though lacking neutralizing capabilities but exhibiting viral-binding activity effectively protected against CVA10 infection. We also evaluated the efficacy of the formalin-inactivated CVA10 (FI-CVA10) vaccine against CVA10 infection. Serum from FI-CVA10-immunized subjects was found to elicit neutralizing antibodies and was subsequently tested in a passive immunization study, demonstrating its effectiveness in preventing CVA10 infection. Notably, passive immunization of Tg mice with AdVLP-immunized splenic lymphocytes, compared to lymphocytes depleted of invariant natural killer T (iNKT) cells, revealed striking differences in outcomes following CVA10 challenge. Mice receiving iNKT-depleted lymphocytes experienced nearly complete mortality by challenge, whereas those receiving AdVLP-immunized lymphocytes achieved a 100 % survival rate. In contrast, Tg mice passively immunized with FI-CVA10-immunized splenic lymphocytes showed no resistance to CVA10 challenge. These findings indicate that FI-CVA10 relies primarily on neutralizing antibodies, rather than cellular immunity, for protection against CVA10 infection. Conversely, AdVLP demonstrates multivalent efficacy against both EV-A71 and CVA10 by inducing iNKT cells and antibody-mediated cellular responses, which together serve as key protective mechanisms against CVA10 infection.