Avoidance of neutralization by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4 and BA.5

To the editors:

Omicron subvarian mutations and responses of neutralizing antibodies.

Panel A shows the genealogy of mutations identified in sub-variants BA.1, BA.2, BA.2.12.1 and BA.4 or BA.5 of SARS-CoV-2 compared to reference WA1. / 2020 insulation. BA.4 and BA.5 have the same sequence of head protein and are thus grouped together. FP represents a synthetic peptide, HR1 heptad replication 1, HR2 heptad replication 1, D N-terminal domain, RBD receptor binding domain, RBM receptor binding motive, 1 subdomain and SD2 subdomain 2. Panel B shows neutralizing antibody titers. The two-dose BNT162b2 reporter RNA was detected by luciferase-based pseudovirus neutralization assays 6 months after receiving the vaccine series and 2 weeks after the third (enhanced) dose from 27 participants. Panel C shows neutralizing antibody titers in participants infected with subA variant BA.1 or BA.2. All infected participants were vaccinated, except for 1 participant who had a negative neutralizing antibody titer. Nine participants showed two or three periods after infection. Neutralizing antibody titers were measured with SARS-CoV-2 reference isolate WA1 / 2020 and omicron BA.1, BA.2, BA.2.12.1 and BA.4 or BA.5 subvariants. Panels B and C show the medians (black bars) numerically and factor differences from other subvariants; The horizontal line shows the lower limit of the definition for analysis.

In recent months, several lines of the omicron (B.1.1.529) variant of coronavirus 2 (SARS-CoV-2) severe acute respiratory syndrome have emerged.1 BA.1 and BA.2 showed significant avoidance of neutralizing antibodies with subvariants.2-5 BA.2.12.1 subvariant is now the predominant strain in the US, while BA.4 and BA.5 are predominant in South Africa (Figure 1A). Subvariants BA.4 and BA.5 have the same sequence of head protein.

We evaluated neutralizing antibody titers against SARS-CoV-2 isolate WA1 / 2020 and 27 participants against BA.1, BA.2, BA.2.12.1 and BA.4 or BA.5 omicron subvariants. 27 participants (range 2 to 113) vaccinated and RNA vaccine enhanced with BNT162b2 messenger (Pfizer – BioNTech) and infected with BA.1 or BA.2 subvariants 29 days ago (Table S1 and S2 Appendix, full text of this letter Available at .org). Participants in the vaccine cohort were excluded if they had a history of SARS-CoV-2 infection or had a positive nucleocapsid serological test, or if they had received another vaccine or immunosuppressive drug against coronavirus disease (Kovid-19) in 2019.

Six months after the first two BNT162b2 vaccinations, the median titer of neutralizing antibody pseudovirus WA1 / 2020 was 124, but less than 20 against all tested omicron subvariants (Figure 1B). Two weeks after the increase in dose, the median titer of neutralizing antibodies increased significantly to 5,783 against WA1 / 2020 isolate, 900 against BA.1, 829 against BA.2, and 410 against BA.2.12.1. subvarian and against BA.4 or BA.5 subvarian 275. These data showed that the neutralizing antibody titer was 6.4-fold against BA.1, 7.0-fold against BA.2, and 7.0-fold against BA.2 / 2020 compared with the response against WA1 / 2020 isolate. 2.12.1, and 21.0 times against BA.4 or BA.5. In addition, the median titer was 2.2 times lower than that of BA.2.12.1 and 3.3 times lower against BA.4 or BA compared with the median titer of neutralizing antibodies against subA variant BA.1. 5 subvariants.

All but one of the participants with Omicron’s BA.1 or BA.2 subvarian were vaccinated against Covid-19. Due to variation in sampling after the onset of infection, some samples may not reflect the highest titers of antibodies (Table S2). Among participants with a history of Kovid-19, the median titer of neutralizing antibodies was 11,050 against WA1 / 2020 isolation, 1,740 against BA.1 sub-variant, 1,910 against BA.2 sub-variant, and 1,150 against BA.2.12.1 sub-variant. , and 590 against the sub-variant BA.4 or BA.5 (Figure 1C). These data show that the median titer of neutralizing antibodies was 6.4 times lower against BA.1, 5.8 times lower against BA.2, and 9.6 times lower against BA.2.12 compared to WA1 / 2020 isolate. 1, and 18.7 times against BA.4 or BA.5. In addition, the median titer was 1.5 times lower for subgroup BA.2.12.1 and 2.9 times lower for subgroup BA.4 or BA.5 compared to median titers for subvariant BA.1. .

These data suggest that sub-variants BA.2.12.1, BA.4, and BA.5 significantly leak neutralizing antibodies from both vaccination and infection. In addition, neutralizing antibody titers against sub-variant BA.4 or BA.5 and (to a lesser extent) titers against sub-variant BA.2.12.1 were lower than the titers against sub-variant BA.1 and BA.2, which neutralizes the SARS -CoV-2 omicron variant. continued to develop with an increase in escape. These findings provide an immunological context for current growth resulting from subvalances BA.2.12.1, BA.4, and BA.5 in populations with high rates of vaccinations and BA.1 or BA.2 infections.

Nicole P. Hachmann, BS
Jessica Miller, BS
Ay-ris Yu. Collier, Doctor of Medical Sciences
John D. Ventura, Ph.D.
Jinzhou Yu, Candidate of Philosophical Sciences.
Marjorie Rowe, BS
Esther A. Bondi, MSN
Olivia Powers, BS
Nehali Surve, MS
Kevin Hall, BS
Dan H. Barush, Candidate of Medical Sciences.
Beth Israel Deacons Medical Center, Boston, MA
[email protected]

supported by a grant (CA260476) National Institutes of Health (NIH), by Massachusetts Pathogen Preparedness Consortiumand by Ragon Institute. Dr. Supported by Barush Musk Foundation. Dr. Collier is supported by the Reproductive Scientists Development Program Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentWith a grant from the Burroughs Wellcome Fund (HD000849) and a grant (AI69309) NIH.

The full disclosure forms provided by the authors are available at NEJM.org with the full text of this letter.

This letter was published on June 22, 2022 on NEJM.org.

  1. 1. Viana R, M, Amoako DG, etc. Rapid epidemic expansion of the SARS-CoV-2 omicron variant in southern Africa. nature 2022; 603:679686.

  2. two. Cele S, Jackson L., Khoury DS, etc. Omicron gets rid of the extensive but incomplete Pfizer BNT162b2 neutralization. nature 2022; 602:654656.

  3. 3. Liu L., Iketani S, Guo Y., etc. Surprising escape of antibodies seen with the omicron variant of SARS-CoV-2. nature 2022; 602:676681.

  4. 4. Yu J., Collier AY, Rowe M, etc. Neutralization of BA.1 and BA.2 variants of SARS-CoV-2 omicron. N Engl J Med 2022; 386:15791580.

  5. 5. Iketani S, Liu L., Guo Y., etc. Antibody avoidance properties of SARS-CoV-2 omicron subline. nature 2022; 604:553556.

Leave a Comment

Your email address will not be published.