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Next-generation SARS-CoV-2 nucleocapsid-based vaccines may provide optimal protection against infection




In a recent study published in International Journal of Infectious DiseasesResearchers have proposed the inclusion of nucleocapsid protein in the vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Research: Nucleocapsid as a candidate for the next-generation COVID-19 vaccine. Image Credit: Treecha / Shutterstock
study: Nucleocapsid as a candidate for next-generation COVID-19 vaccine.. Image Credit: Treecha / Shutterstock

SARS-CoV-2 is an example of an “evolutionary practice” with a variant of concern (VOC) that may continue to emerge. These variants are distinguished by mutations in the viral spike protein. This improves the efficiency of replication, transmission, and antigenic escape. Many SARS-CoV-2 vaccines are based on spike proteins. Given its high mutation frequency, we developed next-generation vaccines by replacing spikes or co-expressing nucleocapsids. Spike protein It could be a viable solution.

Nucleo capsids are located inside and are relatively stable and preserved compared to spikes. Conservation of nucleocapsid is an ideal target for cytotoxic T lymphocytes that correlate with effective clearance of viral particles and milder coronavirus disease 2019 (COVID-19).Researchers also report that they are doing well T cells Reaction to nucleocapsid.

The heterogeneity and evolvability of SARS-CoV-2 in response to selective pressure with therapeutic antibodies and vaccines against spikes may facilitate the emergence of fully resistant variants. The messenger ribonucleic acid (mRNA) vaccine booster is effective against symptomatic infections with SARS-CoV-2 delta, but not against omicron variants. Nevertheless, mRNA boosters can still provide substantial protection against severe illness and death.

Homogeneous and heterogeneous prime boost approach

Multiple doses of the same vaccine, such as a spike-based vaccine, may be referred to as the “homologous prime boost” approach, where the initial dose primes the immune system and additional doses amplify it. This strategy has been shown to enhance the humoral immune response, but the antibody response usually declines over time long before the T cell response diminishes. In contrast, continuous administration of spike-based and nucleocapsid-based vaccines can be defined as a “heterologous prime boost” strategy.

This approach has the potential to enhance the cell-mediated immune response, as previously documented for other pathogens. However, some candidate vaccines require evaluation, comparison, and optimization before implementing this strategy.Or the whole virus BBIBP-CorV and CoronaVac vaccines Inactivated vaccineIt may be useful because it incorporates other viral proteins such as envelopes, nucleocapsids, and matrices.

A study in a population primed with an inactivated vaccine found that boosted immune doses significantly amplified immunogenicity. In particular, heterogeneous prime boosts were more effective than homologous boosts. The limitation of inactivated vaccines is that their immunity is weakened unless they are properly adjuvanted or given in large doses.

Patients with immunodeficiency function as SARS-CoV-2 reservoir

Despite the use of inactivated / mRNA vaccines, studies have identified multimutant antigenic escape variants in immunocompromised patients with prolonged SARS-CoV-2 infection. These individuals can act as a breeding ground for the evolution of the virus, which can lead to spillover to the general public. According to one report, SARS-CoV-2 infection persisted for almost a year in immunocompromised patients. During that time, open reading frames 7b (ORF7b) and ORF8 were completely lost and the virus acquired its own intraframe deletion within the spike sequence.


Implementation of a vaccination policy where using one spike variant vaccine until it is completely suppressed can result in the emergence of another variant. Therefore, vaccination should be designed for broader protection by incorporating conserved nucleocapsids that are essential for viral RNA synthesis and thereby effectively elicit a T cell response.




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