The study focuses on the antibody-mediated response against different variants of SARS-CoV-2.

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

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

Study: The course of SARS-CoV-2 and the immunological history of patients determine the magnitude and potency of antibody-mediated immunity. Image Credit: NIAID

About the study

This study aimed to assess the potency and magnitude of antibodies produced as a result of different immune responses against different variants of SARS-CoV-2.

The team obtained serum samples and compiled the immunological history assessed on the basis of SARS-CoV-2 spike 1 (S1) proteins and spike receptor binding domain (S-RBD) by immunoassay enzymatic (ELISA). Metadata was also collected, including date of serum sample collection, SARS-CoV-2 polymerase chain reaction (PCR) status, and vaccination status. The team then classified the serum samples into four groups: naive (N), vaccinated (V), infected (I), and infected and vaccinated (I).V† Serum samples from groups I and IV were subdivided according to the infecting variant of SARS-CoV-2: infected-Wuhan (IW), infected-alpha (I39 samples), 107 infected delta (I15 samples), infected-Wuhan-vaccinated (IWV60 samples), infected-alpha-vaccinated (IV69 samples), and infected-delta-vaccinated (IV

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

Using the 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 between strains N, V, I and I was quantified.V by titrating neutralizing antibodies to each variant of SARS-CoV-2.

Results

The study results showed that serum samples collected from naive patients had the lowest levels of anti-SARS-CoV-2 S antibodies, as these participants had not been exposed to the SARS-CoV-2 S antigen. Anti-SARS-CoV-2 S antibody levels were higher in infected people than in vaccinated people, while levels were significantly lower in participants who were both infected and vaccinated. In addition, participants who were infected had higher amounts of anti-SARS-CoV-2N antibodies compared to those who were infected and vaccinated.

Concentrations of anti-SARS-CoV-2 Spike and anti-nucleocapsid antibodies in samples from patients with different histories of SARS-CoV-2 exposure.  The name of the antigens is at the top of each panel.  The patient groups are defined as follows: N: naive (yellow);  V: vaccinated (purple);  I: infected (orange);  IV: infected and vaccinated (cyan).  Antibody concentrations are reported in arbitrary units of MSD/ml.  The box plots represent the interquartile range and median values.

Concentrations of antibodies to SARS-CoV-2 tip and nucleocapsid in samples from patients with different histories of SARS-CoV-2 exposure. The name of the antigens is at the top of each panel. The patient groups are defined as follows: N: naive (yellow); V: vaccinated (purple); I: infected (orange); IV: infected and vaccinated (cyan). Antibody concentrations are reported in arbitrary units of MSD/ml. The box plots represent the interquartile range and median values.

Notably, anti-N levels in vaccinated subjects were significantly lower than those in naive subjects. Taken together, these results indicate that exposure to SARS-CoV-2 antigens, both through vaccination and infection, results in higher levels of anti-SARS-CoV-2 antibodies than in vaccinated humans alone.

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

Neutralizing reactions obtained 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 by immunological history (N: naive; V: vaccinated; I: infected; IV: infected and vaccinated).  Neutralizing activity was measured using Wuhan (blue), Alpha (red), Delta (green), and Omicron (gray) spike glycoprotein pseudotypes carrying HIV (SARS-CoV-2) and represented by a 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 repetitions.  The box plots represent the interquartile range and 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 as a function of patient history of exposure to SARS-CoV-2. (A) Patient sera were grouped by immunological history (N: naive; V: vaccinated; I: infected; IV: infected and vaccinated). Neutralizing activity was measured using Wuhan (blue), Alpha (red), Delta (green), and Omicron (gray) spike glycoprotein pseudotypes carrying HIV (SARS-CoV-2) and represented by a 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 repetitions. The box plots represent the interquartile range and 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 group I . haveV showed higher neutralizing antibody titers than those found in all other groups corresponding to each variant tested. On the other hand, infected patients showed different antibody titers against each SARS-CoV-2 variant compared to vaccinated participants. This was seen in the non-significant differences observed in the infected and vaccinated groups corresponding to the Wuhan, Alpha, Delta and Omicron variants of SARS-CoV-2. However, vaccinated patients had significantly higher antibody titres to Omicron, while the neutralizing potency was very low. Taken together, these results indicate that the evolution of SARS-CoV-2 antigens is directional, that is, it evolved to evade antibody-mediated immunity, and that the type and number of viral exposures increase the potency of antibody. -mediated immunity.

The team also noted that patients who were both vaccinated and had a history of Delta virus infection showed the highest neutralizing potency against other variants. According to measures of neutralization bias, people infected with specific variants had different antibody titers against the other variants. This indicates that patients who belonged to the infected group had lower antibody titres 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 comparable to those of vaccinated and infected individuals.

In addition, a comparison of neutralizing antibody titers across all patient groups showed that individuals vaccinated before being infected with the Delta variant or those infected with the Wuhan variant before being vaccinated showed the highest antibody titers against all SARS-CoV infections. 2 variants. This indicates that patients infected before being vaccinated had higher neutralizing potency and antibody titers to each variant.

Conclusion

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

*Important announcement

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

Reference magazine:

  • The course of SARS-CoV-2 and the immunological history of patients determine the extent and potency of antibody-mediated immunity. Maria Manali, Laura A Bissett, Julien Amat, Nicola Logan, Sam Scott, Ellen Hughes, William Harvey, Richard Orton, Emma Thomson, Rory Gunson, Mafalda Viana, Brian Willett, Pablo Ramiro Murcia, bioRxiv 2022.05.06.490867, DOI: https: //doi.org/10.1101/2022.05.06.490867https://www.biorxiv.org/content/10.1101/2022.05.06.490867v1

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