Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern

Dale Kitchin; Simone I Richardson; Mieke A van der Mescht; Thopisang Motlou; Nonkululeko Mzindle; Thandeka Moyo-Gwete; Zanele Makhado; Frances Ayres; Nelia P Manamela; Holly Spencer; Bronwen Lambson; Brent Oosthuysen; Haajira Kaldine; Marizane du Pisanie; Mathilda Mennen; Sango Skelem; Noleen Williams; Ntobeko A B Ntusi; Wendy A Burgers; Glenda G Gray; Linda-Gail Bekker; Michael T Boswell; Theresa M Rossouw; Veronica Ueckermann; Penny L Moore

doi:10.1016/j.xcrm.2022.100535

Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern

Cell Rep Med. 2022 Feb 10;3(3):100535. doi: 10.1016/j.xcrm.2022.100535. eCollection 2022 Mar 15.

Authors

Dale Kitchin^{1

2}, Simone I Richardson^{1

2}, Mieke A van der Mescht³, Thopisang Motlou^{1

2}, Nonkululeko Mzindle^{1

2}, Thandeka Moyo-Gwete^{1

2}, Zanele Makhado^{1

2}, Frances Ayres^{1

2}, Nelia P Manamela^{1

2}, Holly Spencer^{1

2}, Bronwen Lambson^{1

2}, Brent Oosthuysen^{1

2}, Haajira Kaldine^{1

2}, Marizane du Pisanie⁴, Mathilda Mennen⁵, Sango Skelem⁵, Noleen Williams⁵, Ntobeko A B Ntusi^{5

6

7}, Wendy A Burgers^{7

8

9}, Glenda G Gray¹⁰, Linda-Gail Bekker^{7

11}, Michael T Boswell⁴, Theresa M Rossouw³, Veronica Ueckermann⁴, Penny L Moore^{1

2

7

12}

Affiliations

¹ National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS), Johannesburg, South Africa.
² SAMRC Antibody Immunity Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
³ Department of Immunology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
⁴ Division for Infectious Diseases, Department of Internal Medicine, Steve Biko Academic Hospital and University of Pretoria, Pretoria, South Africa.
⁵ Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
⁶ Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
⁷ Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa.
⁸ Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
⁹ Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town, South Africa.
¹⁰ The South African Medical Research Council, Tygerberg, South Africa.
¹¹ The Desmond Tutu HIV Centre, University of Cape Town, Cape Town, South Africa.
¹² Centre for the AIDS Programme of Research in South Africa, Durban, South Africa.

Abstract

The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine has been widely deployed for COVID-19 vaccination programs in resource-limited settings. Here we confirm that neutralizing and binding antibody responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, when tested against multiple SARS-CoV-2 variants. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 4 to 5 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function, and neutralization. These high titer responses are of similar magnitude to humoral immune responses measured in convalescent donors who had been hospitalized with severe illness, and are cross-reactive against diverse SARS-CoV-2 variants, including the neutralization-resistant Omicron (B.1.1.529) variant that currently dominates global infections, as well as SARS-CoV-1. These data have implications for population immunity in areas where the Ad26.COV2.S vaccine has been widely deployed, but where ongoing infections continue to occur at high levels.

Keywords: Ad26.COV2.S; Omicron; SARS-CoV-2; Variant of concern; antibody-dependent cellular cytotoxicity; breakthrough infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Ad26COVS1
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines / therapeutic use
COVID-19* / prevention & control
Humans
SARS-CoV-2 / genetics
Viral Vaccines*

Substances

Ad26COVS1
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Viral Vaccines

Supplementary concepts

SARS-CoV-2 variants

Abstract

Publication types

MeSH terms

Substances

Supplementary concepts

Grants and funding