OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model

Primard, Charlotte; Monchâtre-Leroy, Élodie; Campo, Judith del; Valsesia, Séverine; Nikly, Elsa; Chevandier, Marion; Boué, Franck; Servat, Alexandre; Wasniewski, Marine; Courant, Thomas; Collin, Nicolas; Salguero, Francisco J.; Vert, Alexandre Le; Guyon-Gellin, Delphine; Nicolas, Frédéric

doi:10.3389/fimmu.2023.1188605

Cited by 16 publications

(8 citation statements)

References 36 publications

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“…Indeed, robust titers of N-specific antibodies as well as sufficient levels of N-specific T cells were abundantly found in patients infected with SARS-CoV-2 [ 31 , 32 ]. This has also been confirmed in previous studies, when immunization with monovalent N-based vaccine candidates already showed the immunogenic and protective potential in preclinical studies [ 33 , 34 ]. The suitability of the N-protein has also been demonstrated using MVA as a vaccine vector platform.…”

Section: Introductionsupporting

confidence: 81%

“…No N-specific CD8+ T cells were detected in control-vaccinated and MVA-ST- and MVA-ST/N-vaccinated mice. In previous studies, N-specific T cells have been hypothesized to induce a broader protective potential than S-specific T cells due to the higher conservation of the N-protein [ 34 ]. However, the impact of N-specific T cells for a more rapid protective capacity has not been evaluated in more detail.…”

Section: Discussionmentioning

confidence: 99%

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Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection

Clever,

Limpinsel,

Meyer zu Natrup

et al. 2024

Viruses

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The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later. The protective outcome of MVA-SARS-2-ST/N vaccination correlated with the activation of SARS-CoV-2-neutralizing antibodies (nABs) and substantial amounts of SARS-CoV-2-specific T cells especially in the lung of MVA-SARS-2-ST/N-vaccinated mice. Emergency vaccination with MVA-SARS-2-ST/N just 2 days before lethal SARS-CoV-2 challenge infection resulted in a delayed onset of clinical disease outcome in these mice and increased titers of nAB or SARS-CoV-2-specific T cells in the spleen and lung. These data highlight the potential of a multivalent COVID-19 vaccine co-expressing S- and N-protein, which further contributes to the development of rapidly protective vaccination strategies against emerging pathogens.

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Section: Introductionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection

Clever,

Limpinsel,

Meyer zu Natrup

et al. 2024

Viruses

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“…Vaccination with this prototype led to the generation of non-neutralizing but specific antibodies involved in Fc-mediated cellular responses. In a hamster challenge model, the OVX033 injected with a cholesterol/squalene-based adjuvant provided cross protection against B.1, B.1.617.2 and B.1.1.529 SARS-CoV-2 VOCs, as manifested by reduced weight loss, impaired pulmonary replication of the virus, and reduced lung tissue damage [ 50 ].…”

Section: Development Of N-based Broadly Protective Vaccine Prototypesmentioning

confidence: 99%

Overview of Nucleocapsid-Targeting Vaccines against COVID-19

Rak,

Isakova-Sivak,

Rudenko

2023

Vaccines

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The new SARS-CoV-2 coronavirus, which emerged in late 2019, is a highly variable causative agent of COVID-19, a contagious respiratory disease with potentially severe complications. Vaccination is considered the most effective measure to prevent the spread and complications of this infection. Spike (S) protein-based vaccines were very successful in preventing COVID-19 caused by the ancestral SARS-CoV-2 strain; however, their efficacy was significantly reduced when coronavirus variants antigenically different from the original strain emerged in circulation. This is due to the high variability of this major viral antigen caused by escape from the immunity caused by the infection or vaccination with spike-targeting vaccines. The nucleocapsid protein (N) is a much more conserved SARS-CoV-2 antigen than the spike protein and has therefore attracted the attention of scientists as a promising target for broad-spectrum vaccine development. Here, we summarized the current data on various N-based COVID-19 vaccines that have been tested in animal challenge models or clinical trials. Despite the high conservatism of the N protein, escape mutations gradually occurring in the N sequence can affect its protective properties. During the three years of the pandemic, at least 12 mutations have arisen in the N sequence, affecting more than 40 known immunogenic T-cell epitopes, so the antigenicity of the N protein of recent SARS-CoV-2 variants may be altered. This fact should be taken into account as a limitation in the development of cross-reactive vaccines based on N-protein.

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“…The nucleocapsid proteins of many coronaviruses are highly immunogenic and expressed abundantly in infected cells, making them easy targets for antigen-specific T cells (Cong et al, 2020; Dutta et al, 2020; Hasanpourghadi et al, 2023). Other studies have reported the benefit of vaccination with the nucleocapsid protein of SARS-CoV-2, showing protective immunity in animal models receiving the nucleocapsid protein alone (Primard et al, 2023) or in combination with the spike protein (Chiuppesi et al, 2022; Hasanpourghadi et al, 2023). In our hamster study, we detected cellular immune responses against the spike protein, but not against the nucleocapsid protein.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms

Suzuki-Okutani,

Okamura,

Tanggis

et al. 2024

Preprint

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mRNA vaccines against SARS-CoV-2 were rapidly developed and effective during the pandemic. However, some limitations remain to be resolved, such as the short-lived induced immune response and certain adverse effects. Therefore, there is an urgent need to develop new vaccines that address these issues. While live-attenuated vaccines are a highly effective modality, they pose a risk of adverse effects, including virulence reversion. In the current study, we constructed a live-attenuated vaccine candidate, BK2102, combining naturally occurring virulence-attenuating mutations in the NSP14, NSP1, spike and ORF7-8 coding regions. Intranasal inoculation with BK2102 induced humoral and cellular immune responses in Syrian hamsters without apparent tissue damage in the lungs, leading to protection against a SARS-CoV-2 D614G and an Omicron BA.5 strains. The neutralizing antibodies induced by BK2102 persisted for up to 364 days, which indicated that they confer long-term protection against infection. Furthermore, we confirmed the safety of BK2102 using transgenic (Tg) mice expressing human ACE2 (hACE2), that are highly susceptible to SARS-CoV-2. BK2102 did not kill the Tg mice, even when virus was administered at a dose of 106 plaque-forming units (PFU), while 102 PFU of the D614G strain or an attenuated strain lacking the furin cleavage site (FCS) of the spike was sufficient to kill mice. These results suggest that BK2102 is a promising live-vaccine candidate strain that confers long-term protection without significant virulence.

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OVX033, a nucleocapsid-based vaccine candidate, provides broad-spectrum protection against SARS-CoV-2 variants in a hamster challenge model

Cited by 16 publications

References 36 publications

Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection

Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection

Overview of Nucleocapsid-Targeting Vaccines against COVID-19

Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms

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