T cell immunity remains effective against SARS-CoV-2 Omicron subvariant

In a recent study posted on bioRxiv* Researchers report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant substrains effectively evade B-cell immune responses by altering neutralizing antibody epitopes. increase.

Relatively, T-cell immunity, which primarily targets the viral spike (S) protein, is relatively impervious to SARS-CoV-2 variants and, as a result, may help prevent severe symptoms associated with coronavirus disease 2019. It may still be effective. (COVID-19 (new coronavirus infectious disease).

study: The progressive loss of conserved spike protein-neutralizing antibody sites in the omicron sublineage is balanced by conserved T-cell recognition epitopes. Image credit: Billion Photos / Shutterstock.com

Background

Most viral mutations do not significantly affect its properties, but certain mutations alter the viral transmissibility, disease severity, and efficacy of therapeutics, diagnostic tools, public health measures, and vaccines. There is a possibility. These types of mutational threats have therefore led scientists around the world to continuously screen for emerging and circulating SARS-CoV-2 variants.

Omicron subspecies of SARS-CoV-2 have evolved into multiple sublineages, the earliest of which included BA.1, BA.2, BA.4, and BA.5. More recently, additional Omicron substrains were identified, including BA.4.6, BF.7, BA.2.75, BA.2.75.2, BQ.1.1, and XBB, replacing the previously dominant BA.5 as the dominant substrain. Currently emerging as a circulating stock. .

In addition to understanding the transmissibility, pathogenicity, and immune evasion properties of these new subspecies, researchers also examined immune patterns in human populations. These patterns are often determined by repeated infections with the SARS-CoV-2 variant (VOC) of concern and vaccination dose.

About research

Investigators in the current study utilized well-established artificial intelligence/machine learning-based early-warning systems to identify the omicron substrain in both naïve vaccinated individuals and those who experienced breakthrough infections. BA.4.6, assessed the immune response to BF. 7, BA.2.75, BA.2.75.2, BQ.1.1, and XBB.

Three study cohorts including 18 infection-naive individuals aged 55 years or younger who received three doses of the Pfizer-BioNTech BNT162b2 messenger ribonucleic acid (mRNA) vaccine were evaluated. Fifteen of them aged 60 years and older who received four doses of the BNT162b2 vaccine were also included.

In addition, this study included 3-dose vaccinated individuals who experienced a breakthrough infection with the Omicron substrain. Of these individuals, 14 He had BA.1, 19 He had BA.2, and 17 He had BA.4/BA.5.

Serum neutralization is 50% pseudovirus neutralization (pVN₅₀) Geometric Mean Titer (GMT).In addition, a total of 506 neutralizing B-cell epitopes within cells spike protein We examined the extent to which B-cell epitope conservation corresponds to cross-neutralization of individual SARS-CoV-2 variants.

BA.2.75.2 and XBB escape neutralization by vaccination and Omicron infection

When sera from 3- and 4-vaccinated individuals were tested against BA.4/BA.5, GMT values ​​were 5- to 6-fold lower than the wild-type strain. Similar GMT values ​​were reported when sera from vaccinated individuals with BA.1 infection were tested against BA.4/BA.5. However, history of infection with BA.2 and BA.4/BA.5 led to higher GMT titers for BA.4/BA.5.

Neutralization titers in all three patient groups who experienced breakthrough infection were significantly more to Omicron BA.4.6/BF.7 and BA.2.75 compared to naive SARS-CoV-2 vaccinees was. Furthermore, low titers were observed against BQ.1.1 when sera from naïve and her BA.1 recoverers were tested, whereas BA.2 and BA.4/BA.5 recoverers were less susceptible to this It showed moderately high neutralizing titers against subvariants.

The history of breakthrough infection with BA.2 in vaccinated individuals was greater for BA.4/BA.5 and BA.4.6/BF.7 compared to triple-vaccinated individuals. leading to cross-neutralization. This neutralization was even more pronounced when quadruple vaccinees were considered after breakthrough infection with BA.4/BA.5.

These findings indicate that previous infections with some Omicron sublineages continue to protect against some of these subvariants. However, BA.2.75.2 and XBB have evolved to induce neutralizing antibody responses in both vaccinated naïve individuals and those who experienced a previous breakthrough infection with her Omicron subvariant. I’ve learned to dodge well.

Conservation of B-cell and T-cell epitopes

Of the 506 neutralizing B-cell epitopes analyzed, 91% contained positions altered by at least one SARS-CoV-2 variant. Up to 43% of B-cell epitopes were partially conserved in Alpha, Beta, and Delta variants, but this conservation dropped to <22% in Omicron BA.1 variants and <12% in BA.2.75.2. significantly decreased. and XBB subvariants.

A total of 260 unique human leukocyte antigen (HLA) class I epitope sequences were analyzed, 244 of which were found in the SARS-CoV-2 wild-type spike protein. Of these epitopes, approximately 27% constituted positions that were mutated in at least one SARS-CoV-2 variant analyzed. Conversely, of the 468 HLA class II epitopes analyzed, 49% were located within the mutated region.

Nevertheless, about 90% of CD8⁺ and CD4⁺ T-cell epitopes were conserved in alpha, beta, and delta variants.Similarly, a high rate of 80% and approximately 70% for CD8⁺ and CD4⁺ Conservation of T-cell epitopes was observed in Omicron BA.2.75.2, BQ.1.1, and XBB strains.

This finding is consistent with previous evidence explaining the maintenance of T-cell immunity against Omicron subvariants in individuals with a history of SARS-CoV-2 wild-type infection.

T-cell epitopes of the wild-type SARS-CoV-2 S glycoprotein, Neutralizing antibody It is largely conserved between variants.

Conclusion

The results of this study indicate that SARS-CoV-2 VOCs are unlikely to break T cell-mediated immunity at the population level.Therefore, T-cell immunity can effectively limit the severity of COVID-19 symptomseven in the absence of neutralizing antibodies.

Taken together, these findings highlight the importance of enhancing T-cell immunity through targeted vaccine strategies that induce CD8⁺ T cell immunity in addition to antibody production.

*Important Notices

medrex sib We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.