Evasion of COVID-19 vaccine-medicated mucosal immunity by SARS-CoV-2 Omicron

In a recent study posted to the medRxiv* preprint server, researchers depicted the evasion of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant to mucosal immunity in SARS-CoV-2 vaccine recipients.

Study: Escape of SARS-CoV-2 variant Omicron to mucosal immunity in vaccinated subjects. Image Credit: Studio Romantic/Shutterstock
Study: Escape of SARS-CoV-2 variant Omicron to mucosal immunity in vaccinated subjects. Image Credit: Studio Romantic/Shutterstock


The SARS-CoV-2 Omicron (B.1.1.529) variant has swiftly replaced previously circulating variants, including Delta, following its first detection on November 24, 2021, and categorization as a variant of concern (VOC) two days later. Omicron outgrew Delta in nations with low (South Africa) and high (Norway) Coronavirus disease 2019 (COVID-19) vaccination coverage alike. In line with Omicron's increased transmissibility, two recent investigations in Norwegian and English households found that the secondary attack rate of COVID-19 was significant when the index case variant was Omicron rather than Delta.

Omicron possessed about 60 mutations relative to other SARS-CoV-2 variants, and among that, around 32 were present in its spike (S) protein region. These mutations enhance the affinity of the Omicron variant to the angiotensin-converting enzyme 2 (ACE2) receptor in hosts, explaining the superior multiplication of Omicron versus Delta in the upper respiratory tract.

Further, these mutations confer substantial SARS-CoV-2 infection/vaccination-induced antibody evasion for Omicron. While SARS-CoV-2-specific antibodies protect vaccinated adults from severe COVID-19, lessons learned from other mucosal diseases show that mucosal antibodies, particularly secretory immunoglobulin A (sIgA), are the most effective at blocking the transmission of respiratory viruses like SARS-CoV-2.

About the study

In the current study, the researchers hypothesized that the SARS-CoV-2 Omicron variant disseminates more quickly than the Delta strain in vaccinated participants as it evades vaccine-mediated mucosal immune responses. The team evaluated mucosal antibody responses to the infections with the SARS-CoV-2 ancestral strain, Omicron, and Delta variants, thereby assessing the postulated hypothesis. 

For this, the authors prospectively gathered nasal epithelial lining fluid (NELF) from 84 otherwise healthy medical personnel from France. These healthcare workers did not have a history of polymerase chain reaction (PCR)-verified SARS-CoV-2 infection and were vaccinated with three shots of the COVID-19 Pfizer-BioNTech messenger ribonucleic acid (mRNA) vaccine 10 to 131 days earlier to NELF procurement. For all participants, NELF was collected before Omicron detection in the geographical region of inclusion, i.e., from December 14 to 31, 2021. Moreover, every volunteer submitted an informed consent before enrolling in the study.

NELF was carefully collected using hydroxylated polyvinyl acetate (PVA) sponges. These sponges were inserted within the inferior turbinate and the nasal septum and left in situ for approximately 15 minutes till they swelled, then softly withdrawn and kept in a 50 ml Falcon tube with 2 ml of saline solution. Simple pressure was used to remove the fluid (nasal secretions+saline) from the sponge, which was then aliquoted and stored at -70°C for further examination.

The VPLEX® SARS-CoV-2 Panel was used to assess IgG and IgA targeting the S of the SARS-CoV-2 Omicron, Delta variants, and ancestor strain. Further, the V-PLEX® Isotyping Panel 1 Human/NHP Kit was used to determine total IgG and IgA levels. Nasal secretions were diluted 10-time before being tested for S-specific and overall IgG and IgA. The V-PLEX® Sector Imager 2400 plate reader was used to collect data, which was then processed using Discovery Workbench 3.0 software.

The ability of NELF antibodies to hinder the adherence of a soluble ACE2 to S of the SARS-CoV-2 Omicron, Delta variants, and the ancestral strain was tested by the multiplex V-PLEX® SARS-CoV-2 Panel 13 ACE2 Kit. Before assessing for binding attenuation, NELF was diluted 10-time. As mentioned above, the data was collected and analyzed using the V-PLEX® Sector Imager 2400 plate reader and the Discovery Workbench 3·0 software, respectively. 

The researchers employed diluent alone as the blank. Further, they computed the percentage inhibition based on the instructions of the manufacturer. Previous studies indicated that this test correlated with viral neutralization tests.

Results and conclusions

The study results indicated that the albumin level in NELF was >100 times lower than in serum, ruling out the likelihood that swabbing nasal fluids inflamed the epithelia, resulting in increased tissue fluid exudation. The authors found that relative to the SARS-CoV-2 Wuhan ancestral strain or Delta variant, mucosal IgA and IgG bind less effectively to the Omicron S protein. In addition, NELF antibodies from COVID-19 vaccine recipients were less effective in hampering the binding of the S protein of the SARS-CoV-2 Omicron mutant to ACE2 than those from the ancestral strain or Delta variant.

Overall, the present study findings showed that the SARS-CoV-2 Omicron strain evaded COVID-19 vaccine-elicited mucosal antibody response more significantly than Delta. Thus, this study possibly explained why Omicron was more likely to spread than existing SARS-CoV-2 variants following its successful worldwide substitution of the Delta variant, including in nations with substantial vaccination coverage.

*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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