Overview of Nucleocapsid-Targeting Vaccines against COVID-19

Abstract

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.

Innate and Adaptive Immune Parameters following mRNA Vaccination in Mice

“…Initial mouse studies with our mRNA vaccines have shown that mRNA-N is highly immunogenic and induces strong N-specific binding antibody and T cell (both CD4 + and CD8 + ) responses, despite there being no neutralizing antibodies. Although only modest effects were achieved, mRNA-N vaccination did protect the mouse and hamster from mouse-adapted SARS-CoV-2 and VOCs, respectively [5,16]. Critically, our study also showed that combined mRNA-N and mRNA-S immunization (mRNA-S+N) protected against Delta and Omicron infection in hamsters, whereas mRNA-S alone only induced mild protection [5].…”

Polarization- and CGR-based binary representations as identifiers of the nucleotide sequences in bioinformatics

“…В качестве анализируемых объектов рассмотрены фрагменты символьных последовательностей, ассоциированных с тремя различными штаммами вируса SARS-CoV-2 (ковида) -«Ухань», «Дельта» и «Омикрон». Вирус SARS-CoV-2 продолжает представлять высокую потенциальную угрозу для человечества [20] вследствие своей высокой антигенной изменчивости [21]. Среди генов, кодирующих белки SARS-CoV-2, значительный интерес для исследований представляет спайк-ликопротеин, или S-белок, оказывающий влияние на проникновение вируса в клетки хозяина [22,23].…”