Study: SARS-CoV-2 evolution and patient immunological history shape the breadth and potency of antibody-mediated immunity. Image Credit: NIAID

Study examines antibody-mediated response against different SARS-CoV-2 variants

In a recent study published on bioRxiv*preprint server, researchers assessed the impact of coronavirus disease 2019 (COVID-19) on antibody-mediated immunity.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been widely reported in people with a history of COVID-19 vaccination or infection with a previous variant. This indicates that immunological heterogeneity exists against SARS-CoV-2 infection.

Study: The course of SARS-CoV-2 and the patient’s immunological history shape the extent and potency of antibody-mediated immunity. Image credit: NIAID

About the study

This study aimed to assess the potency and extent of antibodies produced as a result of different immunological reactions against different variants of SARS-CoV-2.

The team obtained serum samples and compiled an immunological history assessed based on SARS-CoV-2 spike 1 (S1) and spike-receptor binding domain (S-RBD) proteins via an enzyme immunoassay ( ELISA). Metadata including date of serum sample collection, SARS-CoV-2 polymerase chain reaction (PCR) status, and vaccination status were also collected. The team then categorized the serum samples into four groups, namely naïve (N), vaccinated (V), infected (I), and infected and vaccinated (I).V). Serum samples from I and IV the groups were then sub-classified based on the infecting variant of SARS-CoV-2 as Wuhan infected (IO), infected-alpha (Iα39 samples), 107 infected-delta (Iδ15 samples), infected-Wuhan-vaccinated (IVM60 samples), infected-alpha vaccinated (IαV69 samples) and vaccinated delta-infected (IδV).

Serum samples were then processed by testing them against protein S and nucleocapsid (N) protein using an electrochemiluminescence assay to quantify antibody concentrations. Virus neutralization (VNA) tests were also performed on the serum samples using human immunodeficiency virus (HIV) pseudotypes that carried the S protein for SARS-CoV-2 strains Wuhan, Alpha , Delta or Omicron.

Using virus pseudotypes, they also assessed whether each serological sample neutralized the four strains of SARS-CoV-2. In addition, the ability to neutralize the antibody-mediated response was quantified among N, V, I and IV groups by titrating neutralizing antibodies against each variant of SARS-CoV-2.

Results

Study results showed that serum samples collected from naïve patients had the lowest levels of anti-SARS-CoV-2 S antibodies since these participants were not exposed to SARS-CoV antigen. -2 S. Levels of S antibodies were higher in infected people than in vaccinated people, while levels were significantly lower in participants who had been both infected and vaccinated. Additionally, infected participants had higher amounts of anti-SARS-CoV-2N antibodies compared to those who were infected and vaccinated.

SARS-CoV-2 Spike and Nucleocapsid antibody concentrations in samples from patients with different histories of SARS-CoV-2 exposure.  The name of the antigens is indicated at the top of each panel.  Patient groups are defined as N: naïve (yellow);  V: vaccinated (purple);  I: infected (orange);  IV: infected and vaccinated (cyan).  Antibody concentrations are reported in arbitrary units MSD/ml.  The boxplots displayed the interquartile range and the median values.

SARS-CoV-2 Spike and Nucleocapsid antibody concentrations in samples from patients with different histories of SARS-CoV-2 exposure. The name of antigens is displayed at the top of each panel. Patient groups are defined as N: naïve (yellow); V: vaccinated (purple); I: infected (orange); IV: infected and vaccinated (cyan). Antibody concentrations are reported in arbitrary units MSD/ml. The boxplots displayed the interquartile range and the median values.

Notably, anti-N levels in vaccinated individuals were significantly lower than in naïve individuals. Overall, these findings indicated that exposure to SARS-CoV-2 antigens through vaccination and infection resulted in higher amounts of anti-SARS-CoV-2 antibodies compared to those after only the vaccination.

The team found that the neutralizing activity of each sample depended on the infecting variant of SARS-CoV-2 and the immunological history of the respective patient. A consistent reduction in neutralization and antigenic drift could be identified by considering the timeline in which the variants arose.

Neutralizing responses elicited against pseudotyped viruses carrying the S protein of different SARS-CoV-2 variants depending on the patient's exposure history to SARS-CoV-2.  (A) Patient sera were grouped according to immunological history (N: naïve; V: vaccinated; I: infected; IV: infected and vaccinated).  Neutralizing activity was measured using Wuhan (blue), Alpha (red), Delta (green), and Omicron (grey) spike glycoprotein pseudotypes carrying HIV (SARS-CoV-2) and plotted per group of patients (A) and by SARS-CoV-2 variant S (B).  Neutralization was measured at a fixed dilution (1:50).  Each point represents the average of two replicates.  The boxplots displayed the interquartile range and the median values.  Significance levels between patient groups or pseudotyped viruses were tested using the Wilcoxon pairwise test and are shown in the lower panels as connected dot plots.

Neutralizing responses elicited against pseudotyped viruses carrying the S protein of different SARS-CoV-2 variants depending on the patient’s exposure history to SARS-CoV-2. (A) Patient sera were grouped according to immunological history (N: naïve; V: vaccinated; I: infected; IV: infected and vaccinated). Neutralizing activity was measured using Wuhan (blue), Alpha (red), Delta (green) and Omicron (grey) peaks glycoprotein carrying HIV (SARS-CoV-2) pseudotypes and plotted by patient group (A) and by SARS-CoV-2 variant S (B). Neutralization was measured at a fixed dilution (1:50). Each point represents the average of two replicates. The boxplots displayed the interquartile range and the median values. Significance levels between patient groups or pseudotyped viruses were tested using the Wilcoxon pairwise test and are shown in the lower panels as connected dot plots.

In addition, patients belonging to the IV group showed higher neutralizing antibody titers than those found in all other groups corresponding to each variant tested. On the other hand, infected patients displayed varying antibody titers against each SARS-CoV-2 variant compared to vaccinated participants. This was noted in the insignificant differences observed in the infected and vaccinated groups corresponding to the SARS-CoV-2 Wuhan, Alpha, Delta and Omicron variants. However, vaccinated patients had significantly higher antibody titers against Omicron while the neutralizing potency was very low. Taken together, this indicates that the evolution of SARS-CoV-2 antigens is directional, that is, it evolved to evade antibody-mediated immunity, and that the type and the number of viral exposures affect the potency of antibody-mediated immunity.

The team also noted that patients who were both vaccinated and had a history of Delta infection showed the highest neutralizing power against the rest of the variants. Based on measures of neutralization bias, individuals infected with specific variants had distinct antibody titers against other variants. This indicated that patients in the infected group had lower antibody titers than those who were both vaccinated and infected. In contrast, the neutralizing antibody titers of patients infected with the Delta variant against the homologous antigen were similar to those of vaccinated and infected individuals.

Additionally, comparison of neutralizing antibody titers across patient groups showed that individuals who were vaccinated prior to being infected with the Delta variant or those who were infected with the Wuhan variant prior to receiving their vaccination had the highest antibody titers against all SARS-CoV-2 variants. This indicated that patients who were infected before being vaccinated had higher neutralizing potency and antibody titers against each variant.

Conclusion

The study findings highlighted the complexity of the impact of SARS-CoV-2 infection on human immunity. The researchers believe the current study will improve epidemiological models to predict future SARS-CoV-2 transmission trends. Additionally, further studies are needed to understand the effects of prior exposure to SARS-CoV-2 on the manifestation and outcome of COVID-19.

*Important Notice

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

Journal reference:

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