Distinct SARS-CoV-2 antibody reactivity patterns elicited by natural infection and mRNA vaccination

Abstract

We analyzed data from two ongoing COVID-19 longitudinal serological surveys in Orange County, CA., between April 2020 and March 2021. A total of 8476 finger stick blood specimens were collected before and after a vaccination campaign. IgG levels were determined using a multiplex antigen microarray containing antigens from SARS-CoV-2, SARS, MERS, Common CoV, and Influenza. Twenty-six percent of specimens from unvaccinated Orange County residents in December 2020 were SARS-CoV-2 seropositive; out of 852 seropositive individuals 77 had symptoms and 9 sought medical care. The antibody response was predominantly against nucleocapsid (NP), full length, and S2 domain of spike. Anti-receptor binding domain (RBD) reactivity was low and not cross-reactive against SARS S1 or SARS RBD. A vaccination campaign at the University of California Irvine Medical Center (UCIMC) started on December, 2020 and 6724 healthcare workers were vaccinated within 3 weeks. Seroprevalence increased from 13% pre-vaccination to 79% post-vaccination in January, 93% in February, and 99% in March. mRNA vaccination induced higher antibody levels than natural exposure, especially against the RBD domain and cross-reactivity against SARS RBD and S1 was observed. Nucleocapsid protein antibodies can be used to distinguish vaccinees to classify pre-exposure to SARS-CoV-2 Previously infected individuals developed higher antibody titers to the vaccine than non pre-exposed individuals. Hospitalized patients in intensive care with severe disease reach significantly higher antibody levels than mild cases, but lower antibody levels compared to the vaccine. These results indicate that mRNA vaccination rapidly induces a much stronger and broader antibody response than SARS-CoV-2 infection.

Performance of Immunoglobulin G Serology on Finger Prick Capillary Dried Blood Spot Samples to Detect a SARS-CoV-2 Antibody Response

“…At the population level, naturally infected and vaccinated individuals can be considered a homogenized group, where an anti-S IgG-positive signal indicates seroreactivity. Conversely, individual diagnosis may require further interpretation where anti-S IgG-positive persons are further stratified by their anti-N IgG results and/or clinical information (e.g., vaccination status and prior laboratory results) to determine natural infection from vaccine-elicited immunity ( 27 ). Detection of natural infection by serology alone depends on study design because anti-N IgG signal wanes when the time between exposure and sample collection lengthens ( 28 , 29 ).…”

“…This sample was not included in the data set from which the thresholds were determined; therefore, the logistic regression model was trained in a sample of unvaccinated participants and tested in vaccinated ones ( 38 ). The anti-N threshold was excluded from the cross-validation, as COVID-19 vaccination does not elicit anti-N humoral immunity ( 27 ). A two-way analysis of variance (ANOVA) was used to investigate the relationship between vaccination status and mean anti-S IgG concentration in log 10 AU/mL.…”

Impact of prior infection on SARS-CoV-2 antibody responses in vaccinated long-term care facility staff

“…Our work, along with others [36][37][38], describes the use of nucleoprotein antibody detection as a tool to identify natural infection using serum collected post-vaccination. This assay could be used to further define and refine correlates of protection, or generate a better predictor of breakthrough risk, by stratifying post-vaccination serum into those that had and had not been previously infected.…”

Evaluation of a Novel Multiplex Platform for Simultaneous Detection of IgG Antibodies Against the 4 Main SARS-CoV-2 Antigens

“…The antibody response to SARS-CoV-2 infection is nonhomogenous targeting different epitopes of several proteins. The efficiency of serological testing is dependent on the dynamics and kinetics of the diverse SARS-CoV-2 antibody responses ( 6 ). A wide range of serological immunoassays have been developed against different SARS-CoV-2 antigens; however, most assays are directed against single targets or utmost 2 targets ( 7–9 ).…”