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

Khadija Khan; Farina Karim; Yashica Ganga; Mallory Bernstein; Zesuliwe Jule; Kajal Reedoy; Sandile Cele; Gila Lustig; Daniel Amoako; Nicole Wolter; Natasha Samsunder; Aida Sivro; James Emmanuel San; Jennifer Giandhari; Houriiyah Tegally; Sureshnee Pillay; Yeshnee Naidoo; Matilda Mazibuko; Yoliswa Miya; Nokuthula Ngcobo; Nithendra Manickchund; Nombulelo Magula; Quarraisha Abdool Karim; Anne von Gottberg; Salim S Abdool Karim; Willem Hanekom; Bernadett I Gosnell; COMMIT-KZN Team; Richard J Lessells; Tulio de Oliveira; Mahomed-Yunus S Moosa; Alex Sigal

doi:10.1038/s41467-022-32396-9

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

Nat Commun. 2022 Aug 10;13(1):4686. doi: 10.1038/s41467-022-32396-9.

Authors

Khadija Khan^{1

2}, Farina Karim^{1

2}, Yashica Ganga¹, Mallory Bernstein¹, Zesuliwe Jule¹, Kajal Reedoy¹, Sandile Cele^{1

2}, Gila Lustig³, Daniel Amoako^{4

5}, Nicole Wolter^{4

6}, Natasha Samsunder³, Aida Sivro^{3

7}, James Emmanuel San⁸, Jennifer Giandhari⁸, Houriiyah Tegally^{8

9}, Sureshnee Pillay⁸, Yeshnee Naidoo⁸, Matilda Mazibuko¹, Yoliswa Miya¹, Nokuthula Ngcobo¹, Nithendra Manickchund¹⁰, Nombulelo Magula¹¹, Quarraisha Abdool Karim^{3

12}, Anne von Gottberg^{4

6}, Salim S Abdool Karim^{3

12}, Willem Hanekom^{1

13}, Bernadett I Gosnell¹⁰; COMMIT-KZN Team; Richard J Lessells⁸, Tulio de Oliveira^{8

9

14}, Mahomed-Yunus S Moosa¹⁰, Alex Sigal^{15

16

17

18}

Collaborators

COMMIT-KZN Team:
Thandeka Khoza, Theresa Smit, Emily Wong

Affiliations

¹ Africa Health Research Institute, Durban, South Africa.
² School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
³ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.
⁴ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
⁵ School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
⁶ School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
⁷ Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa.
⁸ KwaZulu-Natal Research Innovation and Sequencing Platform, Durban, South Africa.
⁹ Centre for Epidemic Response and Innovation (CERI), School of Data Science and Computational Thinking, Stellenbosch University, Stellenbosch, South Africa.
¹⁰ Department of Infectious Diseases, Nelson R. Mandela School of Clinical Medicine, University of KwaZulu-Natal, Durban, South Africa.
¹¹ Division of Internal Medicine, Nelson R. Mandela School of Medicine, University of Kwa-Zulu Natal, Durban, South Africa.
¹² Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
¹³ Division of Infection and Immunity, University College London, London, UK.
¹⁴ Department of Global Health, University of Washington, Seattle, WA, USA.
¹⁵ Africa Health Research Institute, Durban, South Africa. alex.sigal@ahri.org.
¹⁶ School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa. alex.sigal@ahri.org.
¹⁷ Centre for the AIDS Programme of Research in South Africa, Durban, South Africa. alex.sigal@ahri.org.
¹⁸ Max Planck Institute for Infection Biology, Berlin, Germany. alex.sigal@ahri.org.

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Antibodies, Neutralizing
Antibodies, Viral
COVID-19* / prevention & control
Humans
Neutralization Tests
SARS-CoV-2
Spike Glycoprotein, Coronavirus* / genetics

Substances

Antibodies, Neutralizing
Antibodies, Viral
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2

Grants and funding

R01 AI138546/AI/NIAID NIH HHS/United States