COVID-19 mRNA vaccines offer protection against Omicron variant in pregnancy

In a recent study published in the medRxiv* preprint server, researchers analyzed antibody and fragment crystallizable (Fc)-receptor binding profiles of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), including Omicron, among two-dose messenger ribonucleic acid (mRNA)-vaccinated pregnant women.

Study: Preserved recognition of Omicron Spike following COVID-19 mRNA vaccination in pregnancy. Image Credit: LightField Studios/ShutterstockStudy: Preserved recognition of Omicron Spike following COVID-19 mRNA vaccination in pregnancy. Image Credit: LightField Studios/Shutterstock

Background

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 during the initial vaccine trials, resulting in delayed vaccine rollouts in this population. Soon after the emergency use authorization (EUA) of COVID-19 vaccines, studies including the pregnant population were conducted and demonstrated robust antibody titers after mRNA vaccination throughout pregnancy.

Subsequently, the emergence of the SARS-CoV-2 Omicron variant has led to a global surge of COVID-19 cases. Animal studies indicate that vaccine-induced Fc-mediated opsonophagocytosis and cytotoxicity protect from severe SARS-CoV-2 infections. Moreover, pregnant individuals exhibit fully functional Fc-response after the two doses of the mRNA vaccine. However, the COVID-19 mRNA vaccine-induced antibody-mediated protection against emerging SARS-CoV-2 Omicron variant and other VOCs in pregnant women is not well established.

The study

In this study, the researchers determined the receptor-binding domain (RBD) or spike (S)-specific antibody isotype binding titers and Fcγ receptor binding of SARS-CoV-2 Omicron variant and other VOCs in two-dose Pfizer (BNT62b2) or Moderna (mRNA-1273)-vaccinated pregnant women.

Uncomplicated single pregnant women who are 18 years or older were enrolled for the study after submitting informed consent. After two to four weeks of two-dose Moderna and Pfizer vaccination, 10 samples were collected each from the two vaccination groups.

The RBD antigens of the SARS-CoV-2 wildtype (WT), alpha, beta, delta VOCs, and Omicron were collected from Sino-Biologicals and Moderna Incorporated, respectively. Further, 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 Luminex multiplexing assay.

Results

The results indicated that the immunoglobulin G (IgG), IgA, IgM isotype-specific binding capacity of Moderna and Pfizer vaccine-induced antibodies in pregnant women were largely preserved across the Delta, WT, Alpha, and Beta VOC' RBDs. In contrast, there was a 16 to 24-fold and 10 to 23-fold reduction in IgG, IgA, and IgM binding for the Pfizer and Moderna vaccine-induced immune responses to the 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 the pregnant Pfizer vaccine recipients.

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 the Pfizer vaccine recipients. However, Moderna vaccine responses across all three isotypes to Omicron were lower than its response to the WT SARS-CoV-2.

Despite the significant reduction in Omicron-specific isotype binding in Moderna-vaccinated pregnant women, there were comparable levels of Omicron recognition between the Moderna and Pfizer mRNA vaccines due to the overall, more uniform or higher antibody titers induced by Moderna vaccines.

Moderna and Pfizer vaccine-induced RBD-binding antibodies against the WT, Alpha, Beta, and Delta VOCs were able to bind across all Fc-receptors. However, the vaccine-induced Omicron RBD-specific antibodies lost all Fc-receptor binding. Despite this, the Pfizer and Moderna vaccine-induced S-specific antibodies against the WT, Alpha, Beta, Delta, and Omicron VOCs showed detectable binding across all Fc-receptors. Further, the Omicron S-specific antibodies binding to the phagocytic FcγR2a and cytotoxic Fcgγ3a Fc-receptors were relatively more preserved after both vaccinations.

Conclusions

The study findings demonstrated a lower detectable Omicron-specific isotype immunity following Pfizer and Moderna vaccinations. The Fc-receptor binding to the Omicron RBD was nearly absent in these vaccines; however, the FcγR2a- and Fcgγ3a Fc-receptor binding to the Omicron S protein was relatively preserved after both vaccinations.

Thus, regardless of the loss of neutralization, the preservation of Omicron S recognition and Fc-receptor binding after the mRNA vaccination attenuates the severity and mortality rates associated with the SARS-CoV-2 Omicron infection among pregnant women.

The study provides insights into the persistence of extra-neutralizing properties of mRNA vaccine-induced antibodies resulting in protection against the Omicron variant. The present findings can guide future vaccination and booster vaccine campaigns for pregnant women. However, further studies are required to determine whether the Fc-receptor recruitment alone can confer robust protection against Omicron, the effects of booster vaccination on Fc-receptor recruiting qualities, and the duration of the Fc functions.

*Important notice

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

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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