Impact of COVID-19 infection and vaccination on antibody response

A recent study posted to the medRxiv* preprint server assessed the impact of coronavirus disease 2019 (COVID-19) and its vaccination on antibody responses.

Study: Both COVID-19 infection and vaccination induce high-affinity cross-clade responses to SARS-CoV-2 variants. Image Credit: Telnov Oleksii/Shutterstock
Study: Both COVID-19 infection and vaccination induce high-affinity cross-clade responses to SARS-CoV-2 variants. Image Credit: Telnov Oleksii/Shutterstock


Various studies have reported the induction of higher neutralization potency by three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations as compared to that of double vaccinations or convalescent individuals. However, antibody titers have been reported to be significantly lower in the case of the SARS-CoV-2 Omicron variant as compared to those for the wildtype (WT) or the Delta strains.

About the study

In the present study, the researchers examined the affinity and concentration of antibodies against the spike (S) protein of the receptor-binding domains (RBD) of the SARS-CoV-2 WT, Delta, and Omicron strains. They also assessed the influence of COVID-19 and its vaccination on antibody concentration and affinity.

The team obtained heparin plasma samples from 50 pre-Omicron patients who were hospitalized at the University Hospital Zurich, Zurich, Switzerland. Among these 50 samples, 49 were assessed for immunoglobulin G (IgG) reactivity against the WT S protein. Microfluidic antibody affinity profiling (MAAP) was used to evaluate the complicated antibody affinity in SARS-CoV-2-infected plasma samples. The team also analyzed the anti-Omicron affinity of patients who were diagnosed with a pre-Omicron infection or had received vaccines in the pre-Omicron period.

The pre-Omicron samples were examined using MAAP for SARS-CoV-2 WT, Delta, and Omicron RBD. The team also assessed the antibody isotypes and subtypes in the samples and estimated the antibody affinities and concentrations in the serum samples. Furthermore, antibody affinity and concentration profiles were characterized into four cohorts: (1) infected but not vaccinated; (2) non-infected but vaccinated; (3) infected and vaccinated; (4) treated with a combination of two monoclonal antibodies, called REGN-COV.

The team also evaluated the levels of IgG, IgG1, IgG2, IgG3, IgG4 and IgA, IgM, antibodies against the WT S ectodomain (ECD), the WT S1, the WT S2, the WT RBD, the Omicron RBD, the Delta RBD, and the nucleocapsid (NC) proteins. Furthermore, they ascertained the correlation of antibody affinity and concentration with parameters like age, gender, the number of vaccinations, disease severity, and treatment with REGN-COV.


The study results showed that the eligible patients had a median age of 65 years while the median number of days post-onset (DPO) of disease manifestation was 12. A total of 19 patients reported COVID-19 history.

There was a significant decline in the affinity of monoclonal antibodies against the SARS-CoV-2 Omicron RBD. Among the 50 pre-Omicron samples studied, 41 included two patients who had no history of prior COVID-19 or vaccination, eight who had a history of COVID-19 but were not vaccinated, 20 who had never been infected but were vaccinated with either BNT162b2 or messenger ribonucleic acid (mRNA)-1273 vaccines, and 11 who had a history of both prior COVID-19 and vaccination.

The antibody affinity constants ranged between 3.59 µM-1 and 943.3 µM-1, indicating an almost 250-fold affinity range. The IgG concentrations were between three and 49,074 nM. The team also observed an overall reduction in the affinity constants of the antibodies in the case of Omicron as compared to the WT and the Delta strains.

Moreover, there were no substantial differences in the affinity constants of the quantifiable and non-quantifiable samples between any of the antigens, serum samples, or samples that had an infection and/or a vaccine-induced response. However, an increase in the evasion of antibody binding was noted for Omicron.

Overall, following a SARS-CoV-2 vaccination or infection, the antibody response was less susceptible to a substantial decline in Omicron binding as compared to that in monoclonal antibodies.

Antibody profiling showed that the antibody response was predominated by IgG, followed by IgA and IgM. Except for IgG2, all IgG subtypes were responsible for the IgG response against the SARS-CoV-2 S domains. The team also found significant levels of IgG against the SARS-CoV-2 NC in almost all patients who were positive for SARS-CoV-2.        

Furthermore, the researchers found a remarkable positive correlation among the antibody isotypes or subtypes, which could be attributed to the presence of all domains within the viral S-ECD. Notably, true correlations were found between IgG1 and IgG, while spurious correlations were found between IgM, IgG, and IgG2. Disease severity was positively associated with the antibody reactivity against the NC protein, for the IgG1, IgG3, and IgA while an increasing number of vaccinations was negatively associated with NC for IgG1 and IgA.

Overall, the study findings showed that the SARS-CoV-2 WT and Delta S proteins could induce a potent polyclonal immune response against the Omicron S with comparable antibody affinity. The researchers believed that post-infection and/or vaccination, B-cell-mediated immunity could elicit a response that was robust enough to protect against newly emerging SARS-CoV-2 variants. 

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Bhavana Kunkalikar

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.


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