Performing Department
(N/A)
Non Technical Summary
Avian influenza (AI) is among the most economically important diseases affecting poultry and poses a significant threat to the sustainability of the poultry industry worldwide. Over the past two decades, outbreaks of AI, especially involving highly pathogenic avian influenza (HPAI), have caused severe economic losses in many countries, including the United States (U.S.). Notably, the spread of HPAI in the U.S. in 2014-2015 affected 50 million domestic birds and resulted in an estimated loss of $3.3 billion. Currently, the U.S. has been facing another devastating outbreak of HPAI that began in 2022 and as of August 3, 2023 has affected 58.7 million birds in 47 states, surpassing the previous record of 2014-2015 outbreakand standing out as the most significant animal disease event in the history of the U.S.Vaccination is the most cost-effective and humane method for the control and prevention of viral diseases in livestock and poultry. However, viruses like avian influenza virus (AIV), which are constantly mutating, require vaccine platform(s) that can be rapidly developed and deployed in response to emerging strains. Thus, flexible vaccine platforms that enable rapid updates on AIV antigens to match circulating viruses in endemic areas or newly emerging viruses in non-endemic countries are needed. We will tackle this problems by developing novel vaccine delivery platforms for HPAI based on a new condorpox virus vector and on a self-amplifying RNA technology platform. Additionally, we will also develop serological assays that will enable differentiation of vaccinated from infected animals. The outcomes of the proposed project will have a significant impact on animal health and on the sustainability of the poultry industry worldwide.
Animal Health Component
100%
Research Effort Categories
Basic
10%
Applied
70%
Developmental
20%
Goals / Objectives
Our long-term goal is to develop rapid response vaccine delivery platforms and companion DIVA diagnostics for effective control of HPAI in endemic and non-endemiccountries. The specific aims of our project are:Aim 1: To develop novel rapid response vaccine delivery platforms for effective protection against HPAI in poultry. We aim to develop two innovative plug-and-play vaccine platforms, combining the versatility of CRISPR/Cas9 with a novel CDPV vector or the power of RNA technology with a novel self-amplifying Senecavirus A-RNA platform. These platforms will be engineered to incorporate the haemagglutinin gene (HA) of contemporary H5N1 viruses, and their capacity to express HA will be evaluated in vitro (Aim 1a and 1b) while their immunogenicity will be assessed in chickens in vivo (Aim 1c). The protective efficacy of the CRISPox- and SASVex platforms will be compared through immunization/challenge experiments (Aim 1d). The vaccine candidate demonstrating the highest level of protection in these experimental challenge trials will be further evaluated in a field trial conducted in poultry farms with high prevalence of avian influenza outbreaks (Aim 1e); andAim 2: To develop and validate a companion DIVA diagnostic for HPAI. To complement the vaccine platforms developed in Aim 1, we will develop DIVA compatible serological assays (indirect and blocking ELISAs) that will enable differentiation of antibody responses elicited by the vaccines or by natural infection with AIV.
Project Methods
The overall goal of the proposed projectis to developrapid response vaccine delivery platforms and companion DIVA diagnostic assays to improve our ability to combat HPAI.The aims of the proposed project and approaches used to achieve these aims are outlines below:Aim 1: To develop novel rapid response vaccine delivery platforms for effective prevention of HPAI in poultry.In this aim, we propose to develop two novelvaccine delivery platforms consisting of a novela novel poxvirus vector (CDPV) combined with CRISPR/Cas9 editing technology; anda self-amplifying viral RNA platform.Aim 2: To develop and validate a companion DIVA diagnostic for HPAI.In this objective we will focus on the development and validation of reliable HPAI H5-specific diagnostic assays that are DIVA compatible and complementary to the vaccine platforms developed in Aim 1. Our efforts will focus on the development and validation of ELISA-based serological assays.