Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Aug 10;13(1):4686.
doi: 10.1038/s41467-022-32396-9.

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

Khadija Khan  1   2 , Farina Karim  1   2 , Yashica Ganga  1 , Mallory Bernstein  1 , Zesuliwe Jule  1 , Kajal Reedoy  1 , Sandile Cele  1   2 , Gila Lustig  3 , Daniel Amoako  4   5 , Nicole Wolter  4   6 , Natasha Samsunder  3 , Aida Sivro  3   7 , James Emmanuel San  8 , Jennifer Giandhari  8 , Houriiyah Tegally  8   9 , Sureshnee Pillay  8 , Yeshnee Naidoo  8 , Matilda Mazibuko  1 , Yoliswa Miya  1 , Nokuthula Ngcobo  1 , Nithendra Manickchund  10 , Nombulelo Magula  11 , Quarraisha Abdool Karim  3   12 , Anne von Gottberg  4   6 , Salim S Abdool Karim  3   12 , Willem Hanekom  1   13 , Bernadett I Gosnell  10 ; COMMIT-KZN Team; Richard J Lessells  8 , Tulio de Oliveira  8   9   14 , Mahomed-Yunus S Moosa  10 , Alex Sigal  15   16   17   18
Collaborators, Affiliations

Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

Khadija Khan et al. Nat Commun. .

Erratum in

  • Author Correction: Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection.
    Khan K, Karim F, Ganga Y, Bernstein M, Jule Z, Reedoy K, Cele S, Lustig G, Amoako D, Wolter N, Samsunder N, Sivro A, San JE, Giandhari J, Tegally H, Pillay S, Naidoo Y, Mazibuko M, Miya Y, Ngcobo N, Manickchund N, Magula N, Karim QA, von Gottberg A, Abdool Karim SS, Hanekom W, Gosnell BI; COMMIT-KZN Team; Lessells RJ, de Oliveira T, Moosa MS, Sigal A. Khan K, et al. Nat Commun. 2022 Oct 13;13(1):6057. doi: 10.1038/s41467-022-33371-0. Nat Commun. 2022. PMID: 36229444 Free PMC article. No abstract available.

Abstract

SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to Omicron BA.1 including substitutions in the spike receptor binding domain. Here we isolated live BA.4 and BA.5 viruses and measured BA.4/BA.5 neutralization elicited by BA.1 infection either in the absence or presence of previous vaccination as well as from vaccination without BA.1 infection. In BA.1-infected unvaccinated individuals, neutralization relative to BA.1 declines 7.6-fold for BA.4 and 7.5-fold for BA.5. In vaccinated individuals with subsequent BA.1 infection, neutralization relative to BA.1 decreases 3.2-fold for BA.4 and 2.6-fold for BA.5. The fold-drop versus ancestral virus neutralization in this group is 4.0-fold for BA.1, 12.9-fold for BA.4, and 10.3-fold for BA.5. In contrast, BA.4/BA.5 escape is similar to BA.1 in the absence of BA.1 elicited immunity: fold-drop relative to ancestral virus neutralization is 19.8-fold for BA.1, 19.6-fold for BA.4, and 20.9-fold for BA.5. These results show considerable escape of BA.4/BA.5 from BA.1 elicited immunity which is moderated with vaccination and may indicate that BA.4/BA.5 may have the strongest selective advantage in evading neutralization relative to BA.1 in unvaccinated, BA.1 infected individuals.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Escape of BA.4 and BA.5 from BA.1 elicited immunity in unvaccinated participants.
a Daily Covid-19 cases (purple, left axis) and excess deaths (orange, right axis) in South Africa. b Combined fraction of BA.4 and BA.5 in South Africa and the US according to GISAID deposited sequence data. Prevalence was calculated by dividing the number of submitted BA.4 and BA.5 sequences by total submitted sequences per 2-week period starting February 15, 2022. c Percentage of South Africans vaccinated over time. d Neutralization of BA.4 and BA.5 compared to BA.1 virus by BA.1 infection elicited neutralizing immunity in n = 24 unvaccinated participants. Numbers are geometric mean titer (GMT) FRNT50. Dashed line is most concentrated plasma tested. e Geometric mean (GM) of fold-drops in neutralization and their 95% confidence intervals for BA.4 and BA.5 relative to BA.1 calculated from (d). For panels (d) and (e), orange points represent BA.1, yellow BA.4, and pink BA.5. p-values were determined by a two-sided Wilcoxon rank sum test and represented as ***0.001-0.0001. Exact p-values were 4.4 × 10−4 for both BA.4 and BA.5. Source data are provided as a Source Data file.
Fig. 2
Fig. 2. Escape of BA.4 and BA.5 from immunity elicited by vaccination combined with BA.1 breakthrough infection.
a Neutralization of ancestral virus with the D614G substitution, BA.1, BA.4 and BA.5 by vaccine elicited neutralizing immunity with BA.1 breakthrough infection in n = 15 participants. Numbers are geometric mean titer (GMT) FRNT50. Dashed line is most concentrated plasma tested. b Geometric mean (GM) of fold- drops in neutralization and their 95% confidence intervals for BA.4 and BA.5 relative to BA.1 calculated from (a). c GM of fold-drops in neutralization and their 95% confidence intervals for BA.1, BA.4 and BA.5 relative to ancestral/D614G virus calculated from (a). For all panels, green points are values for ancestral/D614G, orange points are BA.1, yellow points are BA.4, and pink points are BA.5. p-values were determined by a two-sided Wilcoxon rank sum test and represented as **0.01-0.001, ***0.001-0.0001, ****<0.0001. Exact p-values were 7.9 × 10−3 for BA.1, 9.7 × 10−5 for BA.4, and 1.9 × 10−4 for BA.5. Source data are provided as a Source Data file.
Fig. 3
Fig. 3. Escape of BA.4 and BA.5 from immunity elicited by vaccination combined in the absence of BA.1 infection.
a Neutralization of ancestral/D614G, BA.1, BA.4 and BA.5 by vaccine elicited neutralizing immunity in n = 18 participants. Numbers are geometric mean titer (GMT) FRNT50. Dashed line is most concentrated plasma tested. b Geometric mean (GM) of fold-drops in neutralization and their 95% confidence intervals for BA.4 and BA.5 relative to BA.1 calculated from (a). c GM of fold-drops in neutralization and their 95% confidence intervals for BA.1, BA.4 and BA.5 relative to ancestral/D614G virus calculated from (a). For all panels, green points are values for ancestral/D614G, orange points are BA.1, yellow points are BA.4, and pink points are BA.5. p-values were determined by a two-sided Wilcoxon rank sum test and represented as ****<0.0001. Exact p-values were 7.2 × 10−5 for BA.1, 3.2 × 10−5 for BA.4, and 2.4 × 10−5 for BA.5. Source data are provided as a Source Data file.
See this image and copyright information in PMC

References

    1. Cele, S. et al. Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization. Nature, 10.1038/s41586-021-04387-1 (2021). - PMC - PubMed
    1. Rössler, A., Riepler, L., Bante, D., von Laer, D. & Kimpel, J. SARS-CoV-2 Omicron variant neutralization in serum from vaccinated and convalescent persons. N. Engl. J. Med.10.1056/NEJMc2119236 (2022). - PMC - PubMed
    1. VanBlargan, L. A. et al. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies. Nat. Med., 10.1038/s41591-021-01678-y (2022). - PMC - PubMed
    1. Richardson, S. I. et al. SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals. Cell Host Microbe, 10.1016/j.chom.2022.03.029 (2022). - PMC - PubMed
    1. Planas D, et al. Considerable escape of SARS-CoV-2 Omicron to antibody neutralization. Nature. 2022;602:671–675. doi: 10.1038/s41586-021-04389-z. - DOI - PubMed

Publication types

Substances