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

Abstract

Antibodies to the nucleocapsid (N) antigen are suggested to be used to monitor infections after COVID-19 vaccination, as first generation subunit vaccines are based on the spike (S) protein. We used multiplex immunoassays to simultaneously measure antibody responses to different fragments of the SARS-CoV-2 S and N antigens for evaluating the immunogenicity of the mRNA-1273 (Spykevax) and the BNT162b2 (Comirnaty) vaccines in 445 health care workers. We report a >4-fold increase post-vaccination of IgG levels to the full length (N FL) and C-terminus of N (N CT) in 5.2% and 18.0% of individuals, respectively, and of IgA in 3.6% (N FL) and 9.0% (N CT) of them. The increase in IgG levels and avidity was more pronounced after Spykevax than Comirnaty vaccination (36.2% vs 13.1% for N CT, and 10.6% vs 3.7% for N FL). Data suggest the induction of cross-reactive antibodies against the N CT region after administering these S-based vaccines, and this should be taken into account when using N seropositivity to detect breakthroughs.

Heterologous Immune Responses of Serum IgG and Secretory IgA Against the Spike Protein of Endemic Coronaviruses During Severe COVID-19

“…This effect was augmented after the booster and in response to all variants of concern ( Figure 1C ). For reasons not fully understood, two individuals showed a mild increase in antibodies that reacted with the nucleocapsid protein, a finding that has also been reported in another study of seronegative individuals receiving BNT162b2 ( 20 ). However, the observed responses to spike proteins demonstrate the utility of the microarray platform for parallel detection of multiple protein-specific immune responses.…”

Cellular Immunity—The Key to Long-Term Protection in Individuals Recovered from SARS-CoV-2 and after Vaccination

“…Patients who have recovered from SARS-CoV-2 presumably acquire cellular immunity to various viral antigens, while the vaccine creates immunity only against the spike protein, which may be the reason for the significantly reduced reinfection rate in patients who have recovered from SARS-CoV-2. However, we could not confirm or dismiss this presumption, as we did not test the immune response to other viral antigens [ 27 , 28 , 29 , 30 ]. Due to the importance of T-cell immunity, the development of a new vaccine that will primarily stimulate cellular immunity has begun.…”

Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01E vaccination is associated with protection

“…But, to our knowledge, no previous research has aimed to investigate the possibility of within-pathogen cross-reactivity, i.e., the capacity of a monoclonal Ab that has matured to bind to a cognate Ag from a given pathogen to additionally bind, perhaps with lower affinity, to other noncognate Ags from the same pathogen. Such a phenomenon may be common in nature (23,24) but may have remained unnoticed due to lack of interest or technological limitations allowing broad Ag screening. However, the paradigm of the one-to-one lock-and-key Ag-Ab interaction is shifting toward a more nuanced several-to-several model.…”