Development of a broad-spectrum vaccine against enterovirus based on adenovirus expression viral-like particles

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. 

Biography:

Dr. Yen-Hung Chow is a senior principal Investigator and professor at the Institute of Infectious Disease and Vaccinology (NIIDV), National Health Research Institutes (NHRI), Taiwan since 2019 until now. He studies the respiratory syncytia virus and enteroviruses virulence and host pathogenesis, and the relevant vaccine development. He received his PhD degree in 1997 at the Graduate School of Life Sciences, National Defense Medical Center, Taiwan. He then joined the research group of Prof. Dimitrov at the Laboratory of Experimental and Computational Biology, National Cancer Institute, National Institutes of health, USA in 2000-2002 for his postdoctoral fellow. He then moved to the Department of Infectious Disease, University of Georgia, Athens, GA, USA  to be a senior postdoctoral fellow in 2002-2005.  He obtained the position of an assistant Investigator at the NIIDV, NHRI in 2006.  He has published more than 60 research articles in SCI journals and over 15 granted patents.