Title : Virus/mutation-agnostic vaccines
Abstract:
Respiratory RNA viruses often mutate into new variants with subsets ravaging public health as escape mutants that render contemporary vaccines and antivirals ineffective from time to time. We have serendipitously developed an innovative approach to vaccine development against respiratory viruses. Our initial research demonstrated that a virulent influenza virus (IFV) could be easily transformed into an influenza vaccine by incubating IFV with an excessive amount of zanamivir in vitro. This new approach has the advantage that the vaccine also acts as a virus/mutation-agnostic antiviral as well as a vaccine potentiator in one package. We demonstrated that intranasal administration of the zanamivir-crippled IFV A/Puerto Rico/8/34 (PR8) dubbed zPR8 elicited adaptive immune responses against PR8 as a safe influenza vaccine. In addition, zPR8 conferred rapid but transient protection of mice against lethal challenges by the mouse coronavirus (CoV) MHV1 in an adaptive immunity-independent manner as a virus/mutation-agnostic antiviral. No appreciable production of interferon-alpha within the lung was induced by zPR8 itself post-administration; however, zPR8 inexplicably amplified CoV-induced interferon responses as an interferon multiplier. zPR8 also converted a lethal dose of CoV into a safe vaccine against repeat CoV infections as a vaccine potentiator. It is conceivable that the development of a modular system with a variety of influenza viruses disabled by a variety of neuraminidase inhibitors (NAI-IFV) capable of converting a myriad of villain viruses into safe vaccines as vaccine potentiators may enable rapid generation of vaccines in response to a surge of unknown viruses away from a Sisyphean cycle that requires characterization of unknown viral mutations that never end.
