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2 results on '"Rohayem, Jacques"'

1. 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

Author

Horvath, Dennis, Temperton, Nigel J., Mayora-Neto, Martin, da Costa, Kelly, Cantoni, Diego, Horlacher, Reinhold, Günther, Armin, Brosig, Alexander, Morath, Jenny, Jakobs, Barbara, Groettrup, Marcus, Hoschuetzky, Heinz, Rohayem, Jacques, ter Meulen, Jan, Horvath, Dennis, Temperton, Nigel J., Mayora-Neto, Martin, da Costa, Kelly, Cantoni, Diego, Horlacher, Reinhold, Günther, Armin, Brosig, Alexander, Morath, Jenny, Jakobs, Barbara, Groettrup, Marcus, Hoschuetzky, Heinz, Rohayem, Jacques, and ter Meulen, Jan

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.

Published
2023

2. PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy.

Author

Koerner, Julia, Horvath, Dennis, Herrmann, Valerie L., MacKerracher, Anna, Gander, Bruno, Yagita, Hideo, Rohayem, Jacques, and Groettrup, Marcus

Subjects
IMMUNE checkpoint proteins, DOUBLE-stranded RNA, CYTOTOXIC T cells, IMMUNOTHERAPY, ANTIGEN receptors, TOLL-like receptors, ANTIGEN presenting cells
Abstract

With emerging supremacy, cancer immunotherapy has evolved as a promising therapeutic modality compared to conventional antitumor therapies. Cancer immunotherapy composed of biodegradable poly(lactic-co-glycolic acid) (PLGA) particles containing antigens and toll-like receptor ligands induces vigorous antitumor immune responses in vivo. Here, we demonstrate the supreme adjuvant effect of the recently developed and pharmaceutically defined double-stranded (ds)RNA adjuvant Riboxxim especially when incorporated into PLGA particles. Encapsulation of Riboxxim together with antigens potently activates murine and human dendritic cells, and elevated tumor-specific CD8+ T cell responses are superior to those obtained using classical dsRNA analogues. This PLGA particle vaccine affords primary tumor growth retardation, prevention of metastases, and prolonged survival in preclinical tumor models. Its advantageous therapeutic potency was further enhanced by immune checkpoint blockade that resulted in reinvigoration of cytotoxic T lymphocyte responses and tumor ablation. Thus, combining immune checkpoint blockade with immunotherapy based on Riboxxim-bearing PLGA particles strongly increases its efficacy. PLGA based cancer immunotherapy incorporating antigen and TLR ligands has resulted in enhancement of the anti-tumour response. Here, the authors explore the use of a defined double stranded RNA adjuvant, Riboxxim, and test its incorporation with PLGA immunotherapy in the context of in vivo tumour models and show enhanced induction of the anti-tumour response. [ABSTRACT FROM AUTHOR]

Published
2021
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