Abstract
Pigs are believed to be one of the important sources of emerging human and swine influenza viruses (SwIV). Influenza virus conserved peptides have the potential to elicit cross-protective immune response, but without the help of potent adjuvant and delivery system they are poorly immunogenic. Biodegradable polylactic-co-glycolic acid (PLGA) nanoparticle (PLGA-NP) based vaccine delivery system enhances cross-presentation of antigens by the professional antigen presenting cells. In this study, Norovirus P particle containing SwIV M2e (extracellular domain of the matrix protein 2) chimera and highly conserved two each of H1N1 peptides of pandemic 2009 and classical human influenza viruses were entrapped in PLGA-NPs. Influenza antibody-free pigs were vaccinated with PLGA-NPs peptides cocktail vaccine twice with or without an adjuvant, Mycobacterium vaccae whole cell lysate, intranasally as mist. Vaccinated pigs were challenged with a virulent heterologous zoonotic SwIV H1N1, and one week later euthanized and the lung samples were analyzed for the specific immune response and viral load. Clinically, pigs vaccinated with PLGA-NP peptides vaccine had no fever and flu symptoms, and the replicating challenged SwIV was undetectable in the bronchoalveolar lavage fluid. Immunologically, PLGA-NP peptides vaccination (without adjuvant) significantly increased the frequency of antigen-specific IFNγ secreting CD4 and CD8 T cells response in the lung lymphocytes, despite not boosting the antibody response both at pre- and post-challenge. In summary, our data indicated that nanoparticle-mediated delivery of conserved H1N1 influenza peptides induced the virus specific T cell response in the lungs and reduced the challenged heterologous virus load in the airways of pigs.
Highlights
Swine influenza is a highly contagious acute respiratory viral disease of pigs, caused by H1N1, H1N2 and H3N2 subtypes of Influenza A virus (IAV)
polylactic-co-glycolic acid (PLGA)-NP containing the vaccine cargo carry a small quantity of surface anchored Ags and they rapidly release upon reconstitution in PBS ( 10 min) called the burst release; while the entrapped Ags in NP release over a period of 4–6 weeks [15]
Our results indicated that PLGA-NP release entrapped M protein 2 ectodomain (M2e)-PP gradually, supporting the principle of depot-effect provided by PLGA-NP under in vivo conditions
Summary
Swine influenza is a highly contagious acute respiratory viral disease of pigs, caused by H1N1, H1N2 and H3N2 subtypes of Influenza A virus (IAV). Current swine flu vaccines are strain specific and they have been failed to induce cross-protection against genetically variant flu viruses [3]. Intramuscularly delivered flu vaccine induces poor mucosal IgA antibody and T cell responses [4]. The highly conserved influenza viral proteins across IAV subtypes are matrix (M1 and M2), nucleocapsid (NP) and stalk domain of hemagglutinin (HA). Promising new generation flu vaccine platforms include use of highly conserved peptides in a vaccine formulation; because, recent developments in biotechnology tools have made the large scale production of antigenic peptides highly feasible at low cost. M2e-PP induced specific immune response, but failed to provide protection from disease (unpublished data)
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