Novel intranasal vaccine targeting SARS-CoV-2 receptor binding domain to mucosal microfold cells and adjuvanted with TLR3 agonist Riboxxim™ elicits strong antibody and T-cell responses in mice

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2023
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Temperton, Nigel
Mayora-Neto, Martin
Da Costa, Kelly
Cantoni, Diego
Horlacher, Reinhold
Günther, Armin
Morath, Jenny
Meulen, Jan ter
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Abstract SARS-CoV-2 continues to circulate in the human population necessitating regular booster immunization for its long-term control. Ideally, vaccines should ideally not only protect against symptomatic disease, but also prevent transmission via asymptomatic shedding and cover existing and future variants of the virus. This may ultimately only be possible through induction of potent and long-lasting immune responses in the nasopharyngeal tract, the initial entry site of SARS-CoV-2. To this end, we have designed a vaccine based on recombinantly expressed receptor binding domain (RBD) of SARS-CoV-2, fused to the C-terminus of C. perfringens enterotoxin, which is known to target Claudin-4, a matrix molecule highly expressed on mucosal microfold (M) cells of the nasal and bronchial-associated lymphoid tissues. To further enhance immune responses, the vaccine was adjuvanted with a novel toll-like receptor 3/RIG-I agonist (Riboxxim™), consisting of synthetic short double stranded RNA. Intranasal prime-boost immunization of mice induced robust mucosal and systemic anti-SARS-CoV-2 neutralizing antibody responses against SARS-CoV-2 strains Wuhan-Hu-1, and several variants (B.1.351/beta, B.1.1.7/alpha, B.1.617.2/delta), as well as systemic T-cell responses. A combination vaccine with M-cell targeted recombinant HA1 from an H1N1 G4 influenza strain also induced mucosal and systemic antibodies against influenza. Taken together, the data show that development of an intranasal SARS-CoV-2 vaccine based on recombinant RBD adjuvanted with a TLR3 agonist is feasible, also as a combination vaccine against influenza.

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ISO 690HORVATH, Dennis, Nigel TEMPERTON, Martin MAYORA-NETO, Kelly DA COSTA, Diego CANTONI, Reinhold HORLACHER, Armin GÜNTHER, Alexander BROSIG, Jenny MORATH, Jan ter MEULEN, 2023. Novel intranasal vaccine targeting SARS-CoV-2 receptor binding domain to mucosal microfold cells and adjuvanted with TLR3 agonist Riboxxim™ elicits strong antibody and T-cell responses in mice. In: Scientific Reports. Springer. 2023, 13(1), 4648. eISSN 2045-2322. Available under: doi: 10.1038/s41598-023-31198-3
BibTex
@article{Horvath2023-03-21Novel-68123,
  year={2023},
  doi={10.1038/s41598-023-31198-3},
  title={Novel intranasal vaccine targeting SARS-CoV-2 receptor binding domain to mucosal microfold cells and adjuvanted with TLR3 agonist Riboxxim™ elicits strong antibody and T-cell responses in mice},
  number={1},
  volume={13},
  journal={Scientific Reports},
  author={Horvath, Dennis and Temperton, Nigel and Mayora-Neto, Martin and Da Costa, Kelly and Cantoni, Diego and Horlacher, Reinhold and Günther, Armin and Brosig, Alexander and Morath, Jenny and Meulen, Jan ter},
  note={Article Number: 4648}
}
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