Week 1, Mar 2024: Antibodies and Nucleocapsid Proteins

The nucleocapsid of a virus, which consists of the capsid enclosing the viral nucleic acid, can be a target for antibody therapies. When a virus infects a host, its nucleocapsid becomes exposed to the immune system, triggering the production of antibodies specific to proteins present on the nucleocapsid's surface, preventing the virus from entering host cells, disrupting its replication cycle, or marking it for destruction by other components of the immune system. Since nucleocapsid proteins are often highly conserved among different strains of a virus, they are attractive targets for antibody therapies that aim to provide broad protection against various strains. 

In the context of therapeutic interventions, monoclonal antibodies targeting nucleocapsid proteins have been developed and tested for their efficacy in treating viral infections. These antibodies can be administered to patients either prophylactically to prevent infection or therapeutically to reduce the severity and duration of symptoms. Just last week, a study by Garrison et al. demonstrated the protective efficacy of a Crimean-Congo hemorrhagic fever virus monoclonal antibody (mAb-9D5) targeting the nucleocapsid protein, which is highly conserved between CCHFV strains. The antibody protected female mice against lethal CCHFV infection or resulted in a significant delay in mean time-to-death in mice that succumbed to disease compared to isotype control animals. 

The nucleocapsid protein has also been a primary research topic for SARS-CoV-2 therapies and impact analyses. The first studies showing improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific mAb were published in late 2022. More recently, Christenson et al. published insights into anti-SARS-CoV-2 assay performance in socioeconomically disadvantaged populations with health disparities. The paper revealed a 96.4% analytical agreement for anti-spike-protein vs anti-nucleocapsid-protein comparisons, and that seroreversion of anti-nucleocapsid reactivity after infection occurred in the disadvantaged population similarly to general populations.  

Last month, an analysis by Kulikowska et al. demonstrated the presence and levels of IgG antibodies directed against the nucleocapsid protein of SARS-CoV-2 patients with multiple sclerosis treated with immunomodulatory therapies. The investigation indicated patients with a prior history of COVID-19 demonstrated statistically significant increases in anti-nucleocapsid antibodies at visit 1, whereas such statistical significance was not observed at visit 2. The results highlighted how antibody levels more accurately reflect the serological status and exhibit a stronger correlation with vaccination than just the presence of antibodies.