Polyanhydride nanovaccine against swine influenza virus in pigs

Abstract

We have recently demonstrated the effectiveness of an influenza A virus (IAV) subunit vaccine based on biodegradable polyanhydride nanoparticles delivery in mice. In the present study, we evaluated the efficacy of ∼200nm polyanhydride nanoparticles encapsulating inactivated swine influenza A virus (SwIAV) as a vaccine to induce protective immunity against a heterologous IAV challenge in pigs. Nursery pigs were vaccinated intranasally twice with inactivated SwIAV H1N2 (KAg) or polyanhydride nanoparticle-encapsulated KAg (KAg nanovaccine), and efficacy was evaluated against a heterologous zoonotic virulent SwIAV H1N1 challenge. Pigs were monitored for fever daily. Local and systemic antibody responses, antigen-specific proliferation of peripheral blood mononuclear cells, gross and microscopic lung lesions, and virus load in the respiratory tract were compared among the groups of animals. Our pre-challenge results indicated that KAg nanovaccine induced virus-specific lymphocyte proliferation and increased the frequency of CD4CD8αα T helper and CD8 cytotoxic T cells in peripheral blood mononuclear cells. KAg nanovaccine-immunized pigs were protected from fever following SwIAV challenge. In addition, pigs immunized with the KAg nanovaccine presented with lower viral antigens in lung sections and had 6 to 8-fold reduction in nasal shedding of SwIAV four days post-challenge compared to control animals. Immunologically, increased IFN-γ secreting T lymphocyte populations against both the vaccine and challenge viruses were detected in KAg nanovaccine-immunized pigs compared to the animals immunized with KAg alone. However, in the KAg nanovaccine-immunized pigs, hemagglutination inhibition, IgG and IgA antibody responses, and virus neutralization titers were comparable to that in the animals immunized with KAg alone. Overall, our data indicated that intranasal delivery of polyanhydride-based SwIAV nanovaccine augmented antigen-specific cellular immune response in pigs, with promise to induce cross-protective immunity.

Liposomal nanoparticle-based conserved peptide influenza vaccine and monosodium urate crystal adjuvant elicit protective immune response in pigs

“…Challenge infection was established using the virulent, zoonotic and highly infectious H1N1 SwIAV (6×10 6 TCID 50 2 mL), 1 mL was administered intranasally as a mist and the other 1 mL intratracheally. 36,37 Blood samples were collected at day post-vaccination (DPV) 0, 21, 35, and 41. From day post-challenge 0 (DPC 0) to euthanasia at DPC 6, rectal temperature of pigs was recorded daily.…”

“…Cells were used in lymphocyte proliferation assay upon stimulation with live SwIAV or pooled peptides, and similarly re-stimulated cells were also subjected to flow cytometry to determine the frequency of lymphocyte subsets. 36,37 Animals were maintained, cared for, fed with ad-libitum food and water, inoculated, had clinical samples collected, and were euthanized as per the approved protocol of the Institutional Animal Care and Use Committee at The Ohio State University. The liposome peptides vaccine and MSU adjuvant were prepared in Pharmaceuticals and Bioengineering Department, Southwest Research Institute, San Antonio, TX, by following the institution-approved biosafety procedures.…”

“…Five micrometer sections of apical, cardiac, and diaphragmatic lung lobes of pigs were stained with H&E and examined microscopically for histopathological changes as described previously. 36,37 The severity of inflammation was scored based on the distribution of lesions and infiltration of mononuclear cells and graded from 0-3.…”

Engineering DNA vaccines against infectious diseases

“…Wafa, et al [25] showed that the polymeric structure affects the intensity of the CD8 + T cell response and increased the protective duration. PA nanoparticle-based vaccines were recently employed for immunizing against swine influenza within pigs [26] and against H5N1 influenza [27]. Shakya, et al [28] discussed the use of PNIPAAm combined with collagen type II as a polymeric adjuvant to reduce the risk of triggering autoimmune responses.…”

Immunology‐Guided Biomaterial Design for Mucosal Cancer Vaccines

“…Other materials were also shown to induce mucosal immunity through the nasal route, utilizing electrostatic interactions with polyelectrolyte MPs, hydrophobic interactions with polyanhydride NPs or interactions with a zwitterionic lipid particle like dilauroylphosphatidylcholine liposomes . The strength of mucoadhesion is determined by the type of bond formed between the polymer and the mucin.…”