Neutralizing antibody responses induced by COVID-19 vaccines against SARS-CoV-2 variants

By Neha MathurMay 19 2022Reviewed by Aimee Molineux

In a recent study published in PLOS Medicine, researchers evaluated the ability of vaccine-induced antibodies to recognize and neutralize various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) in SARS-CoV-2-naive health care workers (HCWs) in the Netherlands.

Background

The World Health Organization (WHO) have assigned VOC status to five SARS-CoV-2 lineages, namely, Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28.P1), Delta (B.1.617.2), and Omicron (B.1.1.529/BA.1), due to their increased transmissibility and virulence.

As per the findings of several randomized clinical trials, the Beta and Delta VOCs are particularly more lethal and potentially diminish the efficacy of several vaccines. A growing body of scientific evidence indicates that Omicron has more resistance to vaccine- and infection-induced immunity compared to other VOCs, thereby reducing the efficacy of all currently used vaccines and necessitating booster immunizations.

Previous studies have focused on one or two vaccines at the most and regression models for directly comparing the humoral responses elicited in response to SARS-CoV-2 VOCs.

About the study

In the present study, researchers performed direct comparisons of the binding and neutralizing activity of antibodies elicited in response to four coronavirus disease 2019 (COVID-19) vaccines against five SARS-CoV-2 VOCs. The team collected blood sera samples from 165 vaccinated but SARS-CoV-2-naive HCWs in the Netherlands who were vaccinated with either of the following four vaccines: BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S. The team repeated the serum sampling five times between January 2021 and January 2022.

They collected the samples from the BNT162b2, mRNA-1273, and AZD122 vaccinees about three weeks post-first vaccination and four weeks post-second vaccination. Since only a single dose of the Ad26.COV2.S vaccine is administered, its recipients were sampled around five and eight weeks post-vaccination. Additionally, they collected serum samples before and after four weeks post BNT162b2 booster shots.

About 65 to 86% of the study population was female in the age group of 35 to 60 years. The number of SARS-CoV-2-naive individuals vaccinated with BNT162b2, mRNA-1273, AZD1222, and Ad26.COV2.S vaccines were 54, 43, 42, and 26, respectively. All of them had received a booster dose of the BNT162b2 vaccine. The team measured the binding of immunoglobulin G (IgG) antibodies elicited in response to the spike (S) proteins of different VOCs using Luminex assays. Pre-fusion stabilized S proteins covalently coupled to v Luminex Magplex beads.

The team used the Median Fluorescence Intensity (MFI) of approximately 50 to 100 beads per well to determine the binding of antibodies, and converted these values into binding antibody units per ml (BAU/ml). They also performed a pseudovirus assay to determine the neutralization titers (IC₅₀), and samples with IC₅₀ <10 IU/ml were defined as having undetectable neutralization.

The authors used univariable and multivariable linear regression analysis to compare changes in antibody titers between the test subjects, and reported results as geometric mean titers (GMTs) with 95% confidence intervals (CIs) while results of mixed models were reported as fold changes with 95% CIs. Lastly, they performed a Spearman’s rank correlation for the comparison between median neutralization titer per vaccine group and reported vaccine efficacy. 

Study findings

The results showed that antibody responses to the SARS-CoV-2 S protein were fairly consistent within the groups, which shows a larger intergroup difference than intragroup difference. They also observed that only one recipient of Ad26.COV2.S had IC50 values under the limit of detection after receiving the primary vaccination series.

Antibody responses in recipients fully vaccinated with mRNA-1273 and BNT162b2 vaccines were significantly higher than that in convalescent individuals four to six weeks from the onset of symptoms, with GMTs of 3077 and 3839 BAU/ml for fully vaccinated individuals compared to 637 BAU/ml for convalescent individuals, respectively.

AZD1222 and Ad26.COV2.S recipients’ responses were significantly lower than both convalescent individuals and mRNA vaccine recipients, with GMTs of 131 and 147 BAU/ml, respectively. The authors observed a significant decline in antibody binding titer for all vaccine groups other than the Ad26.COV2.S group, which showed no decrease in titers between four weeks after the primary vaccination series and before booster vaccination.

Interestingly, neutralizing antibody levels for all groups were substantially higher after booster vaccination compared to initial vaccination. Furthermore, mRNA vaccine recipients showed higher binding responses than adenovirus vaccine recipients among all VOCs.

Conclusions

In this study, the authors compared the ability of four approved COVID-19 vaccines to elicit neutralizing antibodies against different SARS-CoV-2 VOCs and showed that the mRNA vaccines were significantly superior to the adenovirus vector vaccines in terms of inducing neutralizing antibodies against VOCs.

The study findings showed that the neutralizing antibodies in vaccine recipients showed a significant decrease in neutralization efficiency at the peak of their immunity against the VOCs, mainly the Omicron variant, which formed a distinct antigenic cluster.

Notably, recipients of the Ad26.COV2.S vaccine showed no decrease in neutralization titers during a seven-month period, while the mRNA-1273, BNT162b2, and AZD1222 vaccinees showed a significant decline in antibody titers. According to the authors, further research is needed to investigate the reasons behind these interesting observations.