Performing Department
(N/A)
Non Technical Summary
Swine influenza (flu) A virus (SIV) infection in pigs cause huge economic losses. Vaccination is a viable option, but we do not have a potent cross protective vaccine which provides immunity againt constatnly mutating SIV under the field conditions. We have an optimized procedure for developing the dendritic cell targeting mannose labeled chitosan nanoparticle-based whole inactivated SIV vaccine (mChit-SIV-NP), which when inoculated intranasal induces robust local mucosal and systemic immunity and reduces the challenge genetically variant SIV load in the airways of pigs. However, under field conditions vaccinating grown up breeding pigs by intranal route is a challegne, therefore we will evalaure our vaccine efficacy when pigs were vaccinated by simultaneous intranasal and intramuscular route initially and subseuently by injection using ourthermostable bivalent mChit-SIV-NP vaccine, which elicits broadly cross-protective immunity and reduce the viral load in the airways. Our project goal and Objective is to develop a bivalent mChit-SIV-NP vaccine containing inactivated both H1 and H3 SIV subtypes that are predominant in the US swine herdsto elicit long-lasting cross protective immunity against evolving H1 and H3 strains of SIV.The outcome of this project will provide a novel inactivated SIV 'Universal swine-flu vaccine' that could replace the existing commercial SIV vaccines which provide only homologous protection and failed to elicit cross protection against genetically variant field SIVs, attributed to lack of induction of mucosal sIgA and cell-mediated immune responses. The standardized thermostable nanotechnology-based bivalent SIV vaccine could be applied to reduce swine-flu outbreaks in pigs of all ages. Furthermore, this vaccine technology could be applied to mitigate highly pathogenic avian influenza virus (HPAIV) infection in lactating dairy cattle and other respiratory pathogens; importantly, will reduce the public health risk from zoonotic influenza viruses.
Animal Health Component
40%
Research Effort Categories
Basic
20%
Applied
40%
Developmental
40%
Goals / Objectives
Major goals of the project includedevelopment ofa swine influenza virus (SIV) bivalent nanovaccine containing inactivated both H1 and H3 SIV subtypes that are predominant in the US swine herds, administered prime-boost through intranasal and intramuscualr routes followed by systemic boostersto elicit long-lasting cross protective immunity against evolving H1 and H3 strains of SIV under field conditions.ObjectivesObjective 1: To evaluate the protective efficacy of bivalent mChit-SIV-NP vaccine administered by combination of different routes in pigs.Objective 2: To evaluate the cross protective efficacy of bivalent mChit-SIV-NP vaccine. Objective 3: To analyze the duration of efficacy of bivalent mChit-SIV-NP vaccine in pigs.Objective 4: A pilot proof-of-concept study for elucidating the immunogenicity of mChit-NP vaccine delivery platform for HPAI vaccination in dairy cattle.
Project Methods
Objective 1: To evaluate the protective efficacy of bivalent mChit-SIV-NP vaccine administered by combination of different routes in pigs.The current commercial swine-flu vaccine is quadrivalent delivered by intramuscular (IM) route and it provides protection against only genetically identical viruses and does not induce any local mucosal immunity in the upper respiratory tract where the virus predominantly replicates. Moreover, this vaccine lacks periodic updates with widely prevalent SIVs circulating in the swine herds due to practical limitations. Thus, current swine-flu vaccination failed to mitigate transmission of SIVs in the field conditions. We showed that intranasal (IN) vaccination of pigs with mChit-SIV-NP vaccine elicits cross protective immunity in the respiratory tract. To further improve its efficacy, we will test the combination of simultaneous IN-IM, IN and IM routes of vaccination. Furthermore, to make the mChit-SIV-NP formulation a 'Universal swine flu' vaccine, we will make it bivalent by incorporating inactivated both SIV H1 and H3 subtypes, which will elicit heightened cross-protective immunity against variants of both the SIV subtypes that constantly emerge in swine herds. Importantly, the mChit-NP platform will be prepared using quaternized chitosan complex which will make the formulation highly thermostable.Objective 2: To evaluate the cross protective efficacy of bivalent mChit-SIV-NP vaccine. Using an appropriate route of prime-boost vaccination of bivalent mChit-SIV-NP vaccine, Wewill evaluate its efficacy as a 'Universal swine-flu' vaccine by testing against multiple field variants of SIV, which typically have a HA gene identity of around 85-90% to that of vaccine SIVs. Weearlier showed that the mChit-SIV-NP vaccine delivered IN elicitsrobust immunity even when vaccinated to high levels of maternal antibody positive weaned pigs, born to sows vaccinated twice during pregnancy. As per our I-Corps@Ohio survey activity involving over 70 field veterinarians and stakeholders, we understood that in the field conditions vaccination of pregnant sows is practiced in some swine farms, and sows also often get exposed to IAV of both human and swine origin. Therefore, in all our studies we will use conventional pigs procured from local swine vendors, which have various levels of preexisting antibodies. Objective 3: To analyze the duration of efficacy of bivalent mChit-SIV-NP vaccine in pigs.After evaluating the cross protective efficacy of bivalent mChit-SIV-NP vaccine using an ideal prime-boost immunization strategy, it is important to evaluate the duration of immunity in adult pigs. Grow-finisher pigs reach slaughter plant by around 6 months of age and breeding sows are maintained 3-4 years. Due to practical difficulty in care/management and periodic collection of samples from adult pigs, we will perform this study in minipigs maintained over a period of 10-months. We will collect bone marrow samples to determine the duration of virus specific memory B and T cell responses and assess the efficacy by challenging with a heterologous SIV.Objective 4: A pilot proof-of-concept study for elucidating the immunogenicity of mChit-NP vaccine delivery platform for HPAI vaccination in dairy cattle. Until recently, dairy cattle were susceptible only to influenza D viruses worldwide. But since March 18, 2024, they are susceptible to highly pathogenic HPAI H5N1 clade 2.3.4.4b causing severe disease, and very high titers infectious virus shed in milk. So far, the HPAI outbreak has been recorded in 12 states in hundreds of dairy farms throughout the USA. Therefore, development of novel HPAI H5N1 vaccines for dairy cattle to implement effective intervention strategies is at most required. After optimizing the mChit-NP vaccine delivery platform in swine, we hypothesize that the same technology will work efficiently in dairy cattle. Therefore, in this Objective, we will evaluate the immunogenicity of mChit-SIV-NP in calves, and subsequently develop a specific mChit-HPAI-NP vaccine and test efficacy in lactating dairy cattle in our Ag-BSL3 facility by leveraging funding from other sources.