A multiadjuvant polysaccharide-amino acid-lipid (PAL) subunit nanovaccine generates robust systemic and lung-specific mucosal immune responses against SARS-CoV-2 in mice

Pandey, B.; Wang, Z.; Jimenez, A.; Bhatia, E.; Jain, R.; Beach, A.; Maniar, D.; Hosten, J.; O'Farrell, L.; Vantucci, C.; Hur, D.; Noel, R. K.; Ringquist, R. M.; Smith, C.; Ochoa, M. A.; Roy, K.

doi:10.1101/2023.05.05.539395

bioRxiv · 10.1101/2023.05.05.539395

A multiadjuvant polysaccharide-amino acid-lipid (PAL) subunit nanovaccine generates robust systemic and lung-specific mucosal immune responses against SARS-CoV-2 in mice

Pandey, B.·Wang, Z.·Jimenez, A.·Bhatia, E.·Jain, R.·Beach, A.·Maniar, D.·Hosten, J.·O'Farrell, L.·Vantucci, C.·Hur, D.·Noel, R. K.·Ringquist, R. M.·Smith, C.·Ochoa, M. A.·Roy, K.

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Abstract

Existing parenteral SARS-CoV-2 vaccines produce only limited mucosal responses, which are essential for reducing transmission and achieving sterilizing immunity. Appropriately designed mucosal boosters could overcome the shortcomings of parenteral vaccines and enhance pre- existing systemic immunity. Here we present a new protein subunit nanovaccine using multiadjuvanted (e.g. RIG-I: PUUC, TLR9: CpG) polysaccharide-amino acid-lipid nanoparticles (PAL-NPs) that can be delivered both intramuscularly (IM) and intranasally (IN) to generate balanced mucosal-systemic SARS-CoV-2 immunity. Mice receiving IM-Prime PUUC+CpG PAL- NPs, followed by an IN-Boost, developed high levels of IgA, IgG, and cellular immunity in the lung, and showed robust systemic humoral immunity. Interestingly, as a purely intranasal vaccine (IN-Prime/IN-Boost), PUUC+CpG PAL-NPs induced stronger lung-specific T cell immunity than IM-Prime/IN-Boost, and a comparable IgA and neutralizing antibodies, although with a lower systemic antibody response, indicating that a fully mucosal delivery route for SARS-CoV-2 vaccination may also be feasible. Our data suggest that PUUC+CpG PAL-NP subunit vaccine is a promising candidate for generating SARS-CoV-2 specific mucosal immunity.

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Pandey, B., Wang, Z., Jimenez, A., Bhatia, E., Jain, R., Beach, A., Maniar, D., Hosten, J., O'Farrell, L., Vantucci, C., Hur, D., Noel, R. K., Ringquist, R. M., Smith, C., Ochoa, M. A., Roy, K.. 2023-05-08. A multiadjuvant polysaccharide-amino acid-lipid (PAL) subunit nanovaccine generates robust systemic and lung-specific mucosal immune responses against SARS-CoV-2 in mice. https://doi.org/10.1101/2023.05.05.539395

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