A Nanoparticle-Poly(I:C) Combination Adjuvant Enhances the Breadth of the Immune Response to Inactivated Influenza Virus Vaccine in Pigs

Intranasal vaccination elicits secretory IgA (SIgA) antibodies in the airways, which is required for cross-protection against influenza. To enhance the breadth of immunity induced by a killed swine influenza virus antigen (KAg) or conserved T cell and B cell peptides, we adsorbed the antigens together with the TLR3 agonist poly(I:C) electrostatically onto cationic alpha-D-glucan nanoparticles (Nano-11) resulting in Nano-11-KAg-poly(I:C) and Nano-11-peptides-poly(I:C) vaccines. In vitro, increased TNF-α and IL-1ß cytokine mRNA expression was observed in Nano-11-KAg-poly(I:C)-treated porcine monocyte-derived dendritic cells. Nano-11-KAg-poly(I:C), but not Nano-11-peptides-poly(I:C), delivered intranasally in pigs induced high levels of cross-reactive virus-specific SIgA antibodies secretion in the nasal passage and lungs compared to a multivalent commercial influenza virus vaccine administered intramuscularly. The commercial and Nano-11-KAg-poly(I:C) vaccinations increased the frequency of IFNγ secreting T cells. The poly(I:C) adjuvanted Nano-11-based vaccines increased various cytokine mRNA expressions in lymph nodes compared to the commercial vaccine. In addition, Nano-11-KAg-poly(I:C) vaccine elicited high levels of virus neutralizing antibodies in bronchoalveolar lavage fluid. Microscopic lung lesions and challenge virus load were partially reduced in poly(I:C) adjuvanted Nano-11 and commercial influenza vaccinates. In conclusion, compared to our earlier study with Nano-11-KAg vaccine, addition of poly(I:C) to the formulation improved cross-protective antibody and cytokine response.

[1]  S. Dhakal,et al.  Poly(I:C) augments inactivated influenza virus-chitosan nanovaccine induced cell mediated immune response in pigs vaccinated intranasally. , 2020, Veterinary microbiology.

[2]  S. Dhakal,et al.  Oral Deliverable Mucoadhesive Chitosan-Salmonella Subunit Nanovaccine for Layer Chickens , 2020, International journal of nanomedicine.

[3]  Fangjia Lu,et al.  Corn-derived alpha-D-glucan nanoparticles as adjuvant for intramuscular and intranasal immunization in pigs. , 2019, Nanomedicine : nanotechnology, biology, and medicine.

[4]  B. Narasimhan,et al.  Surface engineered polyanhydride-based oral Salmonella subunit nanovaccine for poultry , 2018, International journal of nanomedicine.

[5]  Xingguo Cheng,et al.  Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs , 2018, International journal of nanomedicine.

[6]  S. Ichimiya,et al.  Mucosal Immune Response in Nasal-Associated Lymphoid Tissue upon Intranasal Administration by Adjuvants , 2018, Journal of Innate Immunity.

[7]  Fangjia Lu,et al.  Mucosal Immunity and Protective Efficacy of Intranasal Inactivated Influenza Vaccine Is Improved by Chitosan Nanoparticle Delivery in Pigs , 2018, Front. Immunol..

[8]  Y. Yao,et al.  Alpha-D-glucan nanoparticulate adjuvant induces a transient inflammatory response at the injection site and targets antigen to migratory dendritic cells , 2017, npj Vaccines.

[9]  K. Kang,et al.  Polyanhydride nanovaccine against swine influenza virus in pigs. , 2017, Vaccine.

[10]  K. Kang,et al.  Biodegradable nanoparticle delivery of inactivated swine influenza virus vaccine provides heterologous cell‐mediated immune response in pigs , 2017, Journal of controlled release : official journal of the Controlled Release Society.

[11]  S. Suradhat,et al.  Generation of potent porcine monocyte-derived dendritic cells (MoDCs) by modified culture protocol. , 2016, Veterinary immunology and immunopathology.

[12]  K. Kang,et al.  Entrapment of H1N1 Influenza Virus Derived Conserved Peptides in PLGA Nanoparticles Enhances T Cell Response and Vaccine Efficacy in Pigs , 2016, PloS one.

[13]  Y. Yao,et al.  Dendrimer-like alpha-d-glucan nanoparticles activate dendritic cells and are effective vaccine adjuvants. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[14]  R. Kaushik,et al.  Poly I:C adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs , 2014, Vaccine.

[15]  A. Takada,et al.  Comparison of Antiviral Activity between IgA and IgG Specific to Influenza Virus Hemagglutinin: Increased Potential of IgA for Heterosubtypic Immunity , 2014, PloS one.

[16]  Qian Yang,et al.  Comparison of 3 kinds of Toll-like receptor ligands for inactivated avian H5N1 influenza virus intranasal immunization in chicken. , 2013, Poultry science.

[17]  B. Janke,et al.  Clinicopathological features of Swine influenza. , 2013, Current topics in microbiology and immunology.

[18]  Wenjun Ma,et al.  Swine influenza virus vaccines: to change or not to change-that's the question. , 2013, Current topics in microbiology and immunology.

[19]  Tadaki Suzuki,et al.  Mucosal IgA responses in influenza virus infections; thoughts for vaccine design. , 2012, Vaccine.

[20]  D. Irvine,et al.  Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction , 2012, Proceedings of the National Academy of Sciences.

[21]  L. Larsen,et al.  Distribution of sialic acid receptors and influenza A virus of avian and swine origin in experimentally infected pigs , 2011, Virology Journal.

[22]  Barbara Wieland,et al.  Prevalence and risk factors for swine influenza virus infection in the English pig population , 2011, PLOS Currents.

[23]  Amy L. Vincent,et al.  Chapter 3 Swine Influenza Viruses , 2008 .

[24]  A. Vincent,et al.  Swine influenza viruses a North American perspective. , 2008, Advances in virus research.

[25]  T. Ichinohe,et al.  Cross-Protection against H5N1 Influenza Virus Infection Is Afforded by Intranasal Inoculation with Seasonal Trivalent Inactivated Influenza Vaccine , 2007, The Journal of infectious diseases.

[26]  T. Ichinohe,et al.  Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection. , 2006, Microbes and infection.

[27]  S. Dee,et al.  γδ lymphocyte response to porcine reproductive and respiratory syndrome virus , 2005 .

[28]  T. Ichinohe,et al.  Synthetic Double-Stranded RNA Poly(I:C) Combined with Mucosal Vaccine Protects against Influenza Virus Infection , 2005, Journal of Virology.

[29]  S. Dee,et al.  Gammadelta lymphocyte response to porcine reproductive and respiratory syndrome virus. , 2005, Viral immunology.

[30]  P. Wright,et al.  Role of IgA versus IgG in the Control of Influenza Viral Infection in the Murine Respiratory Tract1 , 2004, The Journal of Immunology.

[31]  P. Heinen,et al.  Analysis of the quality of protection induced by a porcine influenza A vaccine to challenge with an H3N2 virus. , 2001, Veterinary immunology and immunopathology.

[32]  F. Belardelli,et al.  Type i interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. , 2001, Immunity.

[33]  T. D. de Bruin,et al.  Cytolytic function for pseudorabies virus-stimulated porcine CD4+ CD8dull+ lymphocytes. , 2000, Viral immunology.

[34]  M. Russell,et al.  Nasal Lymphoid Tissue (NALT) as a Mucosal Immune Inductive Site , 1997, Scandinavian journal of immunology.

[35]  A. Arsenault,et al.  Comparison of murine nasal-associated lymphoid tissue and Peyer's patches. , 1997, American journal of respiratory and critical care medicine.