Study shows that fully vaccinated individuals retain cross-neutralizing memory B cells against SARS-CoV-2 Omicron variant

B cells produce antibodies to protect against viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). But SARS-CoV-2 evolves with more mutations that make it harder for antibodies to identify – making the role of memory B cells that produce broader reactivity even more valuable.

Study: Two doses of mRNA vaccine induce cross-neutralizing memory B cells against SARS-CoV-2 Omicron variant.  Image credit: Viacheslav Lopatin / ShutterstockStudy: Two doses of mRNA vaccine induce cross-neutralizing memory B cells against SARS-CoV-2 Omicron variant. Image credit: Viacheslav Lopatin / Shutterstock

New research recently published in bioRxiv* Preprint server suggests that memory B cells play a significant role in the increased protection against post-vaccination variants of concern. The study found that increases in dormant memory B-cell subgroups showed strong cross-reactivity against several variants, including Omicron.

The study

The research team enrolled 51 healthcare professionals who were fully vaccinated with two-dose Pfizer-BioNTech mRNA vaccine and were willing to donate blood samples. Blood samples were taken 31 days and 146.5 days after receiving the second dose to study antibody levels and the number of circulating memory B cells.

A separate cohort of 40 volunteers who previously recovered from infection with coronavirus disease 2019 (COVID-19) and had acquired natural immunity also donated their blood samples for research.

Neutralizing antibody protection against several SARS-CoV-2 variants of concern

In this study, the researchers investigated the possibilities of vaccine-induced neutralizing antibodies over time. Their focus was neutralizing antibodies that identify and bind to the receptor binding domain as it contains many epitopes. Receptor-binding domain proteins were created using several SARS-CoV-2 strains including the original discovered in Wuhan, Beta and Delta.

Against the Wuhan strain, two doses of the mRNA vaccine produced robust IgG antibody titers with an increase of over 2000-fold a month after vaccination. In addition, IgA titers increased 44-fold after vaccination. Given the greater boost in IgG antibody levels, the researchers suggest that IgG antibodies play a significant role in neutralization.

There was a reduction in vaccine-induced IgG titers against Beta and Delta. The vaccines produced a 2.4-2.7 times for Beta and 1.1 times for Delta. Neutralizing antibodies had a challenging time against variants with mutations that allow them to escape detection. Nevertheless, IgG antibodies had modest success in binding to the receptor binding domain of the variants.

As time went on, vaccine-induced neutralizing antibodies directed against Wuhan and the Delta variant declined. However, with Beta, other neutralizing antibodies in addition to IgG increased over time, resulting in a gradual increase in neutralizing potency.

There was a 1.1-fold increase in IgG levels against the Beta variant months after vaccination. Overall, the range of neutralizing antibodies increased twice against the Beta variant, but decreased by 1.1 times against Delta.

B-memory cells against the variants

While IgG antibodies decreased over time after vaccination, the researchers found the opposite effect in receptor-binding domain-binding IgG + memory B cells. These memory B cells showed a 1.8-fold increase as time went on.

Four subsets of IgG + memory B cells were examined. One month after vaccination, they produced four subgroups, but after 4.9 months, the number of B-memory cells was different.

Resting memory B-cell subsets increased by 3.5-fold, but atypical memory B-cell subset decreased. This led to an expansion of resting memory B cells to compensate for the loss of the atypical subset.

The memory B cells showed strong cross-reactivity when exposed to the receptor binding domains of Beta and Delta. Cross-reactivity against Beta ranged from 73.3% to 79%, while there was 71.4% to 79.3% cross-reactivity against Delta.

Resting memory B-cell subgroup showed increased cross-reactivity against both variants over time, suggesting increased variant reactivity and cellularity.

Omicron drastically reduced the number of IgG antibodies that could bind to its receptor binding domain. The decrease in neutralization against Omicron continued over time, suggesting that the mutations on Omicron offset mature neutralizing reactions.

But to the researcher’s surprise, dormant memory produced B cells similar neutralizing activities as the Beta and Omicron variants. About 59% produced antibodies with cross-neutralization against Beta and 27% produced cross-neutralization against Omicron.

Study restrictions

Because booster shots have only recently been made available, the researchers were unable to study the effect of the third dose on memory B cells over time. For this reason, it is difficult to measure the number of cross-neutralizing memory B cells and how it is associated with cross-neutralizing antibody responses after a third dose. In addition, the current study focuses on neutralizing antibodies, but animal models have shown that protection against non-neutralizing antibodies is also achieved.

*Important message

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

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