Spike-based COVID-19 immunization increases antibodies to nucleocapsid antigen

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Antibodies to SARS-CoV-2 nucleocapsid (N) antigen are typically used to monitor natural infections.
• Current COVID-19 vaccines (mRNA-1273 and BNT162b2) are based on the spike (S) protein, not the N antigen.
• The potential for S-based vaccines to elicit N-antigen antibodies requires investigation for accurate infection monitoring.

Purpose of the Study:

• To evaluate the immunogenicity of mRNA-1273 (Spykevax) and BNT162b2 (Comirnaty) vaccines.
• To assess antibody responses to both spike (S) and nucleocapsid (N) antigens post-vaccination.
• To determine if SARS-CoV-2 S-based vaccines induce antibodies against N antigen fragments.

Main Methods:

• Multiplex immunoassay used to simultaneously measure antibody responses.
• Antibodies to different fragments of SARS-CoV-2 S and N antigens were analyzed.
• Study included 445 health care workers vaccinated with mRNA-1273 or BNT162b2.

Main Results:

• A >4-fold increase in IgG antibodies to N antigen (full length and C-terminus) was observed in 5.2% and 18.0% of individuals, respectively.
• IgA antibodies to N antigen fragments also increased post-vaccination.
• Higher increases in IgG levels and avidity against N antigen fragments were noted after mRNA-1273 vaccination compared to BNT162b2.

Conclusions:

• SARS-CoV-2 S-based vaccines can induce cross-reactive antibodies against the N antigen C-terminus.
• The presence of vaccine-induced N-antigen antibodies may affect the interpretation of serological tests for infection detection.
• Consideration of vaccine-induced N-antigen seropositivity is essential when using N-based assays to identify breakthrough infections.