Cutting Edge: Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity

Matchett, William E.; Joag, Vineet; Stolley, J. Michael; Shepherd, Frances K.; Quarnstrom, Clare F.; Mickelson, Clayton K.; Wijeyesinghe, Sathi; Soerens, Andrew G.; Becker, Samuel; Thiede, Joshua M.; Weyu, Eyob; O’Flanagan, Stephen; Walter, Jeff; Vu, Michelle N; Menachery, Vineet D.; Bold, Tyler D.; Vezys, Vaiva; Jenkins, Marc K.; Langlois, Ryan A.; Masopust, David

doi:10.4049/jimmunol.2100421

Cited by 146 publications

(133 citation statements)

References 15 publications

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“…In this respect, herein, we described the development and immunogenicity of SARS‐CoV‐2 VLP vaccine that incorporates the four structural proteins of the virus, all of which possess T‐cell epitopes. 24 , 25 , 26 , 47 , 48 …”

Section: Discussionmentioning

confidence: 99%

Development and preclinical evaluation of virus‐like particle vaccine against COVID‐19 infection

Yılmaz

İpekoğlu

Bulbul

et al. 2021

Allergy

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Background Vaccines that incorporate multiple SARS‐CoV‐2 antigens can further broaden the breadth of virus‐specific cellular and humoral immunity. This study describes the development and immunogenicity of SARS‐CoV‐2 VLP vaccine that incorporates the four structural proteins of SARS‐CoV‐2. Methods VLPs were generated in transiently transfected HEK293 cells, purified by multimodal chromatography, and characterized by tunable‐resistive pulse sensing, AFM, SEM, and TEM. Immunoblotting studies verified the protein identities of VLPs. Cellular and humoral immune responses of immunized animals demonstrated the immune potency of the formulated VLP vaccine. Results Transiently transfected HEK293 cells reproducibly generated vesicular VLPs that were similar in size to and expressing all four structural proteins of SARS‐CoV‐2. Alum adsorbed, K3‐CpG ODN‐adjuvanted VLPs elicited high titer anti‐S, anti‐RBD, anti‐N IgG, triggered multifunctional Th1‐biased T‐cell responses, reduced virus load, and prevented lung pathology upon live virus challenge in vaccinated animals. Conclusion These data suggest that VLPs expressing all four structural protein antigens of SARS‐CoV‐2 are immunogenic and can protect animals from developing COVID‐19 infection following vaccination.

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Section: Discussionmentioning

confidence: 99%

Development and preclinical evaluation of virus‐like particle vaccine against COVID‐19 infection

Yılmaz

İpekoğlu

Bulbul

et al. 2021

Allergy

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“…In the COVID-19 context, the main transgene of choice has been the SARS-CoV-2 structural surface glycoprotein-coding gene (spike protein), either whole or partial [16]. Nonetheless, the nucleocapsid protein (N) has also been the target of some studies, either alone or in combination with the S protein [17][18][19].…”

Section: The "Trojan Horse" Technologymentioning

confidence: 99%

“…In March of 2020, the World Health Organization (WHO) characterized the public health emergency that had its epicenter in Wuhan (China), later called COVID-19 coronavirus disease 2019 (COVID- 19), as a pandemic [1]. The disease, associated with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immediately required global efforts by the scientific community in the search for treatments, diagnostic tests and vaccines capable of containing the spread of the virus.…”

Section: Introductionmentioning

confidence: 99%

The Rise of Vectored Vaccines: A Legacy of the COVID-19 Global Crisis

Silva

Fonseca

2021

Vaccines

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The COVID-19 pandemic represents a milestone in vaccine research and development in a global context. A worldwide effort, as never seen before, involved scientists from all over the world in favor of the fast, accurate and precise construction and testing of immunogens against the new coronavirus, SARS-CoV-2. Among all the vaccine strategies put into play for study and validation, those based on recombinant viral vectors gained special attention due to their effectiveness, ease of production and the amplitude of the triggered immune responses. Some of these new vaccines have already been approved for emergency/full use, while others are still in pre- and clinical trials. In this article we will highlight what is behind adeno-associated vectors, such as those presented by the immunogens ChaAdOx1, Sputnik, Convidecia (CanSino, Tianjin, China), and Janssen (Johnson & Johnson, New Jersey, EUA), in addition to other promising platforms such as Vaccinia virus MVA, influenza virus, and measles virus, among others.

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“…Its high conservation and universal cytoplasmic expression makes the N protein an attractive complementary target antigen to elicit durable and broadly reactive T cells 23 . Several recent studies highlight the benefits of N as a vaccine antigen in animal models 25–28 .…”

Section: Introductionmentioning

confidence: 99%

“…Several recent studies highlight the benefits of N as a vaccine antigen in animal models [25][26][27][28] .…”

Section: Introductionmentioning

confidence: 99%

Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

Chiuppesi

Nguyen

Park

et al. 2021

Preprint

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Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen Modified Vaccinia Ankara-based SARS-CoV-2 vaccine that co-expresses spike and nucleocapsid antigens. Here, we report COH04S1 vaccine efficacy in animal models. We demonstrate that intramuscular or intranasal vaccination of Syrian hamsters with COH04S1 induces robust Th1-biased antigen-specific humoral immunity and cross-neutralizing antibodies (NAb) and protects against weight loss, lower respiratory tract infection, and lung injury following intranasal SARS-CoV-2 challenge. Moreover, we demonstrate that single-dose or two-dose vaccination of non-human primates with COH04S1 induces robust antigen-specific binding antibodies, NAb, and Th1-biased T cells, protects against both upper and lower respiratory tract infection following intranasal/intratracheal SARS-CoV-2 challenge, and triggers potent post-challenge anamnestic antiviral responses. These results demonstrate COH04S1-mediated vaccine protection in animal models through different vaccination routes and dose regimens, complementing ongoing investigation of this multiantigen SARS-CoV-2 vaccine in clinical trials.

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Cutting Edge: Nucleocapsid Vaccine Elicits Spike-Independent SARS-CoV-2 Protective Immunity

Cited by 146 publications

References 15 publications

Development and preclinical evaluation of virus‐like particle vaccine against COVID‐19 infection

Development and preclinical evaluation of virus‐like particle vaccine against COVID‐19 infection

The Rise of Vectored Vaccines: A Legacy of the COVID-19 Global Crisis

Synthetic Multiantigen MVA Vaccine COH04S1 Protects Against SARS-CoV-2 in Syrian Hamsters and Non-Human Primates

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