The Problem

Swine influenza is an acute respiratory disease of pigs caused by swine influenza A virus (SwIAV). Pigs are naturally vulnerable to SwIAV-associated with secondary bacterial infections and is an economic threat to the global pig industry. Commonly circulating SwIAV strains in swine population are H1N1, H1N2, and H3N2. In the United States, periodically human infections are occurred from some of the SwIAVs. In last two decades, triple reassortant SwIAVs have been isolated from pigs and its association with human infections have been well documented. Therefore, vaccination of pigs is a common practice to reduce the influenza burden in swine industry and to avoid the risk of zoonotic transmission to humans . The SwIAV vaccine inoculated into sows protects the herd from infection and heightens the transfer of maternally-derived antibodies (MDA) to offspring through colostrum. However, a number of studies have revealed that MDA offered various levels of protection against SwIAV infection in piglets . In weaned piglets, MDA interferes with parenteral administered killed/inactivated influenza virus vaccines, resulting in poor induction of antibody responses and documented evidence of vaccine-associated enhanced respiratory disease underscoring the need for an improved vaccine approach.

The Solution

Researches at OSU have developed a mannose conjugated chitosan (mCS) nanoparticle comprising killed antigen (KAg) to target dendritic cells and macrophages which express mannose receptors. In maternal derived antibody (MDA)-positive piglets, prime-boost intranasal inoculation of mCS NPs-KAg vaccine elicited enhanced homologous (H1N2-OH10), heterologous (H1N1-OH7), and heterosubtypic (H3N2-OH4) influenza virus-specific secretory IgA (sIgA) antibody response in nasal passage compared to CS NPs-KAg vaccinates. Upon challenge with a heterologous SwIAV H1N1, the mCS NPs-KAg vaccines augmented H1N2-OH10, H1N1-OH7, and H3N2-OH4 virus-specific sIgA antibody responses in nasal swab, lung lysate, and bronchoalveolar lavage (BAL) fluid; and IgG antibody levels in lung lysate and BAL fluid. samples. In the mCS NPs-KAg vaccinates increased H1N2-OH10 but not H1N1-OH7 and H3N2- OH4-specific serum hemagglutination inhibition titers were observed.

Additionally, mCS NPs-KAg vaccine increased specific recall lymphocyte proliferation and cytokines IL-4, IL-10, and IFNγ gene expression compared to CS NPs-KAg and commercial SwIAV vaccinates in tracheobronchial lymph nodes. The mCS NPs-KAg vaccinates cleared the challenge H1N1-OH7 virus load in upper and lower respiratory tract more efficiently when compared to commercial vaccine. The virus clearance was associated with reduced gross lung lesions. Overall, mCS NP-KAg vaccine intranasal immunization in MDA-positive pigs induced a robust cross-reactive immunity and offered protection against influenza virus.