Comparison of IgA, IgG and neutralizing antibody responses following immunization with Moderna, BioNTech, AstraZeneca, Sputnik-V, Johnson and Johnson, and Sinopharm’s COVID-19 vaccines.
Authors: Adjobimey Tomabu , Meyer Julia , Sollberg Leander , Bawolt Michael , Berens Christina , Kovačević Peđa , Trudić Anika , Parcina Marijo , Hoerauf Achim 
Published: December 2021

Abstract
BACKGROUNDSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have afflicted millions of people in a worldwide pandemic. Several vaccines have been developed to prevent infection and illness. However, the safety and efficacy of most of the vaccines currently available are still being questioned by part of the public opinion. Even if vaccine-resistant individuals represent a minority in most countries, their hesitancy is sufficient to delay the highly desired ‘herd-immunity threshold.’ METHODSIn an ongoing multinational trial, we collected blood samples from 365 adults, 18 years of age or older, vaccinated with mRNA vaccines (Moderna, BioNTech), viral DNA-vectored vaccines (AstraZeneca, Sputnik-V, and Johnson and Johnson), or the attenuated virus vaccine from Sinopharm. Out of the 365 vaccinated individuals included in the study, 41 received two doses of Moderna Biotech's Spikevax, 92 received two doses of BioNTech’s Comirnaty, 52 were vaccinated with two doses of Oxford-AstraZeneca’s Vaxzevria, 34 received one dose of Johnson and Johnson’s Jansen, 35 two doses of Gamaleja’s Sputnik-V and 28 two doses of Sinopharm’s BBIBP-CorV. In addition, 40 received a prime dose of AstraZeneca followed by BioNTech as a booster, whereas 43 received Moderna’s vaccine as a booster after a prime dose of AstraZeneca. After collecting reactogenicity data, the expression of S-Protein binding IgG and IgA were analyzed before and after full vaccination in each group using an automated sandwich ELISA system. In addition, the neutralizing capacity of sera from individuals from all groups was investigated using an ACE-2-RBD neutralizing assay. RESULTSThe main side effects reported included short-term mild-to-moderate pain at the injection site, fatigue, and headache. More severe side effects were reported by vaccinees in the Moderna (10%), AstraZeneca (11%), Johnson and Johnson (5.9%), and Sputnik-V (7.2%) groups. No severe adverse reaction was reported in the BioNTech group, and the Sinopharm vaccinees presented the mildest reactogenicity profile, with 93.8% of the vaccinees declaring no adverse reactions. Moderna’s vaccine induced the highest amounts of SARS-CoV-2 specific IgG, IgA, and serum neutralization activity compared to the other groups. In contrast, people vaccinated with Sinopharm and Johnson and Johnson’s vaccines have the lowest SARS-CoV-2-specific antibody titers. Vaccinees from the Johnson and Johnson group presented significant levels of SARS-CoV-2 specific IgA but not IgG compared to the controls before vaccination. In the Sinopharm group, neither IgG nor IgA expression was significant. In addition, sera from vaccinees of these two groups presented no significant neutralization potential compared to the unvaccinated controls. Significant negative correlations between age and SARS-CoV-2- specific IgG expression were observed in the Johnson and Johnson (r=-0.4414, p=0.009) and Sinopharm (r=-0.6108, p=0.0006) groups. Remarkably, younger vaccinees (18-60 years old) in both Sinopharm and Johnson and Johnson groups produced substantial SARS-CoV-2 specific antibody expression and exhibited significant neutralization potential. While the AstraZeneca vaccine alone induced moderate IgG and IgA expression, the combination with Moderna or BioNTech mRNA vaccines induced higher antibody levels than a double dose of AstraZeneca and similar IgG expression and neutralization potential compared to Moderna, or BioNTech used alone. CONCLUSIONThe results suggest that the Moderna vaccine is the most immunogenic after two doses. AstraZeneca and Sputnik-V presented moderate but significant antibody expression and virus neutralizing properties. Low antibody and neutralization potential was observed in the elderly vaccinated with Sinopharm or Johnson and Johnson vaccines. The data also suggest that heterologous vaccination strategies combining the AstraZeneca DNA vectored vaccines and mRNA vaccines Moderna or BioNTech booster induced more robust antibody and virus neutralization potential compared to their homologous counterparts.