During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including 3 rd dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is less after infection compared to all vaccines evaluated, but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks post-vaccination in some cases. SARS-CoV-2 antibody specificity, breadth and maturation are affected by imprinting from exposure history, and distinct histological and antigenic contexts in infection compared to vaccination.

Electrogenerated chemiluminescence (ECL) is the process in which electrogenerated species undergo electron transfer reactions to form excited states that emit light. Many molecules have the potential to produce ECL, however Ru(bpy) 3 2+ (bpy = 2,2′‐bipyridine) is the most common emitter used for analytical applications. Application of a voltage to an electrode in the presence of an emitter induces light production and allows for the detection of the emitter at very low concentrations. Advantages over other analytical methods include low backgrounds, precise spatial and temporal control over the emission, and the possibility of signal amplification. Commercial systems exist that use ECL to detect numerous clinically relevant analytes with high sensitivity using a variety of assay formats.

Carbon nanotubes, compounded into plastic to create bulk electrodes, form the basis of a novel sensor for biological assays. The nanotubes function as both a solid phase and working electrode for generation of electrochemiluminescence, the detection method used in this system. The Figure shows a scanning electron microscopy image of a composite used for an immunoassay. The bright spots in the image are 10 nm diameter gold colloids covalently attached to antibodies. The inset shows a region of a composite with no gold colloids.

Highlights d Antibodies to four COVID-19 vaccines differed in an observational study in Mongolia d Responses from high to low: Pfizer/BioNTech > AstraZeneca > Sputnik V > Sinopharm d Breakthrough infections in June to early July of 2021 were due mostly to the Alpha variant d After breakthrough infection, high antibody levels are seen in all vaccine groups

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, new vaccine strategies including lipid nanoparticle delivery of antigen encoding RNA have been deployed globally. The BioNTech/Pfizer mRNA vaccine BNT162b2 encoding SARS-CoV-2 spike protein shows 95% efficacy in preventing disease, but it is unclear how the antibody responses to vaccination differ from those generated by infection. Here we compare the magnitude and breadth of antibodies targeting SARS-CoV-2, SARS-CoV-2 variants of concern, and endemic coronaviruses, in vaccinees and infected patients. We find that vaccination differs from infection in the dominance of IgG over IgM and IgA responses, with IgG reaching levels similar to those of severely ill COVID-19 patients and shows decreased breadth of the antibody response targeting endemic coronaviruses. Viral variants of concern from B.1.1.7 to P.1 to B.1.351 form a remarkably consistent hierarchy of progressively decreasing antibody recognition by both vaccinees and infected patients exposed to Wuhan-Hu-1 antigens.