In a recent study published in the medRxiv* Preprint server, the researchers analyzed the crystallizable receptor (Fc) binding profiles of antibodies and fragments of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern, including Omicron, among the Two-dose messenger ribonucleic acid (mRNA) -vaccinated pregnant women.
Studies have shown that SARS-CoV-2 infections are likely to induce severe coronavirus disease 2019 (COVID-19) in pregnant women. However, pregnancy was an exclusion criterion in the initial vaccine trials, which resulted in a delay in the deployment of the vaccine in this population. Shortly after the emergency use authorization (EUA) of the COVID-19 vaccines, studies including the pregnant population were conducted and demonstrated robust antibody titers after mRNA vaccination throughout of pregnancy.
Subsequently, the emergence of the SARS-CoV-2 Omicron variant led to a worldwide increase in COVID-19 cases. Animal studies indicate that the opsonophagocytosis and cytotoxicity induced by the vaccine protect against serious infections with SARS-CoV-2. In addition, pregnant individuals exhibit a fully functional Fc response after the two doses of the mRNA vaccine. However, the antibody-induced protection induced by the COVID-19 mRNA vaccine against the emerging variant of SARS-CoV-2 Omicron and other VOCs in pregnant women is not well established.
In this study, researchers determined the antibody isotype binding titers specific to the receptor binding domain (RBD) or peak (S) and the binding to the Fcγ receptor of the Omicron variant of SARS-CoV-2 and d ‘other VOCs in Pfizer at two doses (BNT62b2) or Pregnant women vaccinated with Moderna (mRNA-1273).
Uncomplicated single pregnant women aged 18 or older were recruited for the study after submitting informed consent. After two to four weeks of Moderna and Pfizer vaccination in two doses, 10 samples were each taken from the two vaccination groups.
Wild type SARS-CoV-2 (WT) RBD antigens, alpha, beta, delta, and Omicron VOCs were collected from Sino-Biologicals and Moderna Incorporated, respectively. In addition, the stabilized S protein of all SARS-CoV-2 VOCs was produced using HEK293 cells. The antigen-specific antibody subclass, isotypes and Fcγ receptor binding of SARS-CoV-2 VOCs were analyzed using the Luminex multiplexing assay.
The results indicated that the specific binding capacity to immunoglobulin G (IgG), IgA, IgM isotypes of antibodies induced by Moderna and Pfizer vaccines in pregnant women was largely preserved in Delta, WT, Alpha and Beta VOC RBDs. In contrast, there was a 16-24-fold and 10-23-fold reduction in IgG, IgA and IgM binding for immune responses induced by Pfizer and Moderna vaccines to Omicron RBD.
Compared to the significant decrease in binding against Omicron RBD, relatively stable anti-Spike IgM and IgG binding antibodies against Omicron and all other VOCs were induced by Pfizer vaccination in pregnant women; however, IgA responses to Omicron were significantly lower in pregnant women receiving Pfizer vaccine.
Moderna vaccine recipients had a more consistent level of anti-Spike IgG and IgM responses and higher IgA responses against all VOCs in pregnant women compared to recipients of the Pfizer vaccine. However, the responses of Moderna vaccine on all three isotypes to Omicron were inferior to its response to WT SARS-CoV-2.
Despite the significant reduction in specific isotypic binding of Omicron in pregnant women vaccinated with Moderna, there were comparable levels of Omicron recognition between Moderna and Pfizer mRNA vaccines due to the overall, more uniform antibody titers. or higher induced by Moderna vaccines.
The RBD-binding antibodies induced by Moderna and Pfizer vaccines against WT, Alpha, Beta and Delta VOCs were able to bind to all Fc receptors. However, the vaccine-induced Omicron RBD specific antibodies lost all binding to the Fc receptor. Despite this, the S-specific antibodies induced by the Pfizer and Moderna vaccines against WT, Alpha, Beta, Delta and Omicron VOCs showed detectable binding on all Fc receptors. In addition, Omicron S-specific antibodies binding to phagocytic FcγR2a and cytotoxic Fcgγ3a Fc receptors were relatively better preserved after the two vaccinations.
Study results demonstrated lower detectable Omicron specific isotypic immunity after Pfizer and Moderna vaccinations. Fc receptor binding to Omicron RBD was almost absent in these vaccines; however, binding of the FcγR2a and Fcgγ3a Fc receptors to the Omicron S protein was relatively preserved after the two vaccinations.
Thus, regardless of loss of neutralization, preservation of Omicron S recognition and Fc receptor binding after mRNA vaccination mitigates the severity and death rates associated with SARS infection. Omicron CoV-2 in pregnant women.
The study provides information on the persistence of extra-neutralizing properties of antibodies induced by the mRNA vaccine, resulting in protection against the Omicron variant. Current results may guide future vaccination and booster vaccination campaigns for pregnant women. However, further studies are needed to determine whether Fc receptor recruitment alone can confer robust protection against Omicron, the effects of booster vaccination on Fc receptor recruitment qualities and duration of Fc functions.
medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.