In a recent study published on the website of the bioRxiv*, 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 there is immunological heterogeneity against SARS-CoV-2 infection.
Study: The course of SARS-CoV-2 and the immunological history of patients determine 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 immunological history assessed based on SARS-CoV-2 spike 1 (S1) proteins and spike-receptor binding domain (S-RBD) via immunoassay -enzymatic (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 classified the serum samples into four groups: naïve (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 (Ia39 samples), 107 infected-delta (Id15 samples), infected-Wuhan-vaccinated (IWV60 samples), infected-alpha vaccinated (IαV69 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 that carried 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 was quantified between strains N, V, I and IV by titrating neutralizing antibodies against each variant of SARS-CoV-2.
The study results showed that serum samples collected from naïve patients had the lowest levels of anti-SARS-CoV-2 S antibodies since these participants had not been exposed to the S antigen of the SARS-CoV-2. Anti-SARS-CoV-2 S antibody levels were higher in infected people than in vaccinated people, while levels were significantly lower in participants who had been both infected and vaccinated. Additionally, participants who had been infected had higher amounts of anti-SARS-CoV-2N antibodies compared to those who had been infected and vaccinated.
Concentrations of antibodies against SARS-CoV-2 tip and nucleocapsid 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. The patient groups are defined as follows: 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 display the interquartile range and the median values.
Notably, anti-N levels in vaccinated individuals were significantly lower than those in naïve individuals. Taken together, these results indicate that exposure to SARS-CoV-2 antigens, both through vaccination and infection, results in higher amounts of anti-SARS-CoV-2 antibodies than in humans. vaccinated people only.
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 patient concerned. A consistent reduction in neutralization and antigenic drift could be identified by considering the chronology of appearance of the variants.
Neutralizing responses elicited against pseudotyped viruses carrying the S protein of different SARS-CoV-2 variants as a function of patient 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 represented by 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 display 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 group IV exhibited higher neutralizing antibody titers than those found in all other groups corresponding to each variant tested. On the other hand, infected patients showed varying 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 titers against 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 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 virus infection showed the highest neutralizing potency against other variants. According to measures of neutralization bias, people infected with specific variants had distinct antibody titers against the other variants. This indicates that patients belonging to 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.
Furthermore, comparison of neutralizing antibody titers across all patient groups showed that individuals who had been vaccinated before being infected with the Delta variant or those who had been infected with the Wuhan variant before being vaccinated showed the highest antibody titers against all SARS-CoV-2 variants. This indicates that patients who were infected before being vaccinated had higher neutralizing potency and antibody titers against each variant.
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. Additionally, further studies are needed to understand the effects of prior exposure to SARS-CoV-2 on the manifestation and outcome of COVID-19.
*bird is important
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health behavior or be treated as established information.
- 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/10.1101/2022.05.06.490867, https://www.biorxiv.org/content/10.1101/2022.05.06.490867v1