Title : Development of a broad-spectrum vaccine against enterovirus based on adenovirus expression viral-like particles
Abstract:
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 EV-A71, CVA16, or CVA10, AdVLP immunization significantly reduced muscle, spinal cord, and brain’s viral amounts and protected animal from disease occurrence. 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 CVA10 by inducing iNKT cells and antibody-mediated cellular responses, which together serve as key protective mechanisms against CVA10 infection.