COH04S1 and beta sequence-modified vaccine protect hamsters from SARS-CoV-2 variants

The role of SARS-CoV-2 nucleocapsid protein in antiviral immunity and vaccine development

“…Up to now, 9 of the 10 SARS-CoV-2 N-based vaccines employ full length N-protein from SARS-CoV-2 ancestral virus, alone or in combination with other SARS-CoV-2 structural proteins [ 69–81 ]. Although with different compositions (vector-based [ 69 , 70 , 73 , 74 , 77 , 78 ], recombinant protein [ 76 , 79 ], or mRNA [ 81 ]) and different vaccination routes (intramuscular [ 69 , 70 , 76 , 78 , 81 ], intradermal [ 73 ], intranasal [ 73 , 77 , 79 ], or intravenous [ 74 ]), these 9 vaccines elicited protective effects in all the preclinical studies with SARS-CoV-2 ancestral virus infection. More importantly, vaccines with full length N-protein conferred protection against infection by the SARS-CoV-2 variants of concern [ 69 , 70 , 76 , 77 , 81 ].…”

“…Although with different compositions (vector-based [ 69 , 70 , 73 , 74 , 77 , 78 ], recombinant protein [ 76 , 79 ], or mRNA [ 81 ]) and different vaccination routes (intramuscular [ 69 , 70 , 76 , 78 , 81 ], intradermal [ 73 ], intranasal [ 73 , 77 , 79 ], or intravenous [ 74 ]), these 9 vaccines elicited protective effects in all the preclinical studies with SARS-CoV-2 ancestral virus infection. More importantly, vaccines with full length N-protein conferred protection against infection by the SARS-CoV-2 variants of concern [ 69 , 70 , 76 , 77 , 81 ]. Additionally, these vaccines with full length N-protein demonstrated high tolerability in clinical trials [ 71 , 72 , 75 ] and 6 of the 9 vaccines elicited production of antibodies with robust binding to the N-protein ( Table 2 ) [ 69–79 , 81 ].…”

Vaccine-induced spike- and nucleocapsid-specific cellular responses maintain potent cross-reactivity to SARS-CoV-2 Delta and Omicron variants

“…We previously developed clinical vaccine candidate COH04S1, a synthetic multi-antigenic modified vaccinia Ankara (sMVA) vector co-expressing full-length S and N antigen sequences based on the Wuhan-Hu-1 reference strain (Chiuppesi et al, 2020). COH04S1 was highly immunogenic in different animal models and protected against ancestral SARS-CoV-2 and VOC in Syrian hamsters and non-human primates (Chiuppesi et al, 2020(Chiuppesi et al, , 2022aWussow, 2022). COH04S1 has been tested in a combined open label and randomized phase 1 clinical trial in healthy adults, demonstrating high tolerability and robust induction of humoral and cellular responses to both S and N antigens (Chiuppesi et al, 2022b).…”

Synthetic modified vaccinia Ankara vaccines confer potent monkeypox immunity in non-human primates and healthy adults

“…Using this platform, which allows rapid generation of sMVA recombinants encoding multiple transgenes, we developed COH04S1, a multiantigen sMVA-based COVID-19 vaccine encoding for Spike (S) and Nucleocapsid (N) antigens. COH04S1 has been extensively tested in small and large animal models, demonstrating robust immunogenicity and protective efficacy against SARS-CoV-2 and its variants through intramuscular and intranasal routes of vaccination 15-17 . Additionally, COH04S1 has been tested in a phase I, randomized, placebo-controlled clinical trial in healthy adults, showing a remarkable safety profile and resulting in the induction of robust and durable humoral and cellular responses to both vaccine antigens 18,19 .…”

“…Using this platform, which allows rapid generation of sMVA recombinants encoding multiple transgenes, we developed COH04S1, a multiantigen sMVA-based COVID-19 vaccine encoding for Spike (S) and Nucleocapsid (N) antigens. COH04S1 has been extensively tested in small and large animal models, demonstrating robust immunogenicity and protective efficacy against SARS-CoV-2 and its variants through intramuscular and intranasal routes of vaccination [15][16][17] .…”