Author: Hong, Jung Joo ; Kim, Chang-Ung ; Lee, Moo-Seung ; Oh, Hanseul ; Jang, Min Seong ; Park, Jung-Eun ; Lee, Pureum ; Kim, Doo-Jin ; Jeong, Ahn Young ; Kim, Jihee

Most coronavirus vaccines focus on the spike (S) antigen, but the frequent mutations in S raise concerns about the vaccine efficacy against new variants. Although additional antigens with conserved sequences are have been tested, the extent to which these vaccines can provide immunity against different coronavirus species remains unclear. In this study, we assessed the potential of nucleocapsid (N) as a coronavirus vaccine antigen. Immunization with MERS-CoV N induced robust immune responses, providing significant protection against MERS-CoV. Notably, MERS-CoV N elicited cross-reactive T cell responses to SARS-CoV-2 N and significantly reduced lung inflammation following a SARS-CoV-2 challenge in the transient hACE2 mouse model. However, in K18-hACE transgenic mice, the vaccine showed limited protection. Collectively, our findings suggest that coronavirus N can be an effective vaccine antigen against homologous viruses, but its efficacy may vary across different coronaviruses, highlighting the need for further research on pan-coronavirus vaccines using conserved antigens.

01 Dec 2022·International Journal of Infectious Diseases

Could nucleocapsid be a next-generation COVID-19 vaccine candidate – author's reply

Letter

Author: Caroen, Scott ; Larson, Christopher ; Reid, Tony R ; Oronsky, Bryan

A review.The main point of this perspective was that nucleocapsid (N),being highly conserved among coronaviruses (CoVs), less mutable than spike(S), and strongly immunogenic, especially for T cells ,which persist for much longer than waning antibodies, is a primary target for a broader and more cross-protective vaccine.Mutations are common in RNA viruses,such as SARS-CoV-2.Their rapid evolution is responsible for the accumulation of genetic changes, particularly when the host is immunodeficient.However, most mutations impact viral fitness deleteriously, especially those involving indispensable proteins, such as N, which not only binds to and protects the RNA genome from degradation but also functions as an antagonist of interferon, one of the main mechanisms of the host innate immune defense.

01 Dec 2022·Journal of Clinical Investigation

Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody

Article

Author: Richner, Justin M ; Richner, Michelle ; Dangi, Tanushree ; Bentley, Kirsten ; Stanton, Richard J ; Penaloza-MacMaster, Pablo ; Class, Jacob ; Visvabharathy, Lavanya ; Koralnik, Igor J ; Sanchez, Sarah ; Chung, Young Rock

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main antigen in all approved COVID-19 vaccines and is also the only target for monoclonal antibody (mAb) therapies. Immune responses to other viral antigens are generated after SARS-CoV-2 infection, but their contribution to the antiviral response remains unclear. Here, we interrogated whether nucleocapsid-specific antibodies can improve protection against SARS-CoV-2. We first immunized mice with a nucleocapsid-based vaccine and then transferred sera from these mice into naive mice, followed by challenge with SARS-CoV-2. We show that mice that received nucleocapsid-specific sera or a nucleocapsid-specific mAb exhibited enhanced control of SARS-CoV-2. Nucleocapsid-specific antibodies elicited NK-mediated, antibody-dependent cellular cytotoxicity (ADCC) against infected cells. To our knowledge, these findings provide the first demonstration in the coronavirus literature that antibody responses specific to the nucleocapsid protein can improve viral clearance, providing a rationale for the clinical evaluation of nucleocapsid-based mAb therapies to treat COVID-19.

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Indication	Highest Phase	Country/Location	Organization	Date
COVID-19	Preclinical	US	EpicentRx, Inc.	-

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