Biology subjects

Paudyal, B.

Publications and source records attributed to Paudyal, B..

3 recordsLinked to original sources

bioRxiv2020

Magnitude and kinetics of T cell and antibody responses during H1N1pdm09 infection in outbred and inbred Babraham pigs

We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize {beta}, {gamma}{delta} T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to day 4-5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from day 5-6 post infection reaching a peak at 9-14 days. {gamma}{delta} cells produced cytokines ex vivo at day 2 post infection, while virus specific IFN{gamma} producing {gamma}{delta} T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4 and {gamma}{delta} cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyse immune responses to influenza.

immunology↗

bioRxiv2020

Simultaneous aerosol and intra-muscular immunization with influenza vaccine induces powerful protective local T cell and systemic Ab immune responses in pigs

A vaccine providing both powerful antibody and cross-reactive T cell immune responses against influenza viruses would be beneficial for both humans and pigs. Here we evaluated intramuscular (IM), aerosol (Aer) and simultaneous immunization (SIM) by both routes in pigs, using the single cycle candidate influenza vaccine S-FLU. After prime and boost immunization pigs were challenged with H1N1pdm09 virus. IM immunized pigs generated high titer of neutralizing antibodies but poor T cell responses, while Aer induced powerful respiratory tract T cell responses, but a low titer of antibodies. SIM pigs combined high antibody titers and strong local T cell responses. SIM pigs showed the most complete suppression of virus shedding and the greatest improvement in pathology. We conclude that SIM regimes for immunization against respiratory pathogens warrant further study.

immunology↗

bioRxiv2020

Protective porcine influenza virus-specific monoclonal antibodies recognize similar haemagglutinin epitopes as humans

Pigs are natural hosts for the same subtypes of influenza A viruses as humans and integrally involved in virus evolution with frequent interspecies transmissions in both directions. The emergence of the 2009 pandemic H1N1 virus illustrates the importance of pigs in evolution of zoonotic strains. Here we generated pig influenza-specific monoclonal antibodies (mAbs) from H1N1pdm09 infected pigs. The mAbs recognized the same two major immunodominant haemagglutinin (HA) epitopes targeted by humans, one of which is not recognized by post-infection ferret antisera that are commonly used to monitor virus evolution. Neutralizing activity of the pig mAbs was comparable to that of potent human anti-HA mAbs. Further, prophylactic administration of a selected porcine mAb to pigs abolished lung viral load and greatly reduced lung pathology but did not eliminate nasal shedding of virus after H1N1pdm09 challenge. Hence mAbs from pigs, which target HA can significantly reduce disease severity. These results, together with the comparable sizes of pigs and humans, indicate that the pig is a valuable model for understanding how best to apply mAbs as therapy in humans and for monitoring antigenic drift of influenza viruses in humans, thereby providing information highly relevant to making influenza vaccine recommendations.

immunology↗