Impact of Age and Severe Acute Respiratory Syndrome Coronavirus 2 Breakthrough Infection on Humoral Immune Responses After Three Doses of Coronavirus Disease 2019 mRNA Vaccine

Francis Mwimanzi; Hope R Lapointe; Peter K Cheung; Yurou Sang; Fatima Yaseen; Rebecca Kalikawe; Sneha Datwani; Laura Burns; Landon Young; Victor Leung; Siobhan Ennis; Chanson J Brumme; Julio S G Montaner; Winnie Dong; Natalie Prystajecky; Christopher F Lowe; Mari L DeMarco; Daniel T Holmes; Janet Simons; Masahiro Niikura; Marc G Romney; Zabrina L Brumme; Mark A Brockman

doi:10.1093/ofid/ofad073

Impact of Age and Severe Acute Respiratory Syndrome Coronavirus 2 Breakthrough Infection on Humoral Immune Responses After Three Doses of Coronavirus Disease 2019 mRNA Vaccine

Open Forum Infect Dis. 2023 Feb 9;10(3):ofad073. doi: 10.1093/ofid/ofad073. eCollection 2023 Mar.

Authors

Francis Mwimanzi¹, Hope R Lapointe², Peter K Cheung^{1

2}, Yurou Sang¹, Fatima Yaseen¹, Rebecca Kalikawe¹, Sneha Datwani¹, Laura Burns³, Landon Young³, Victor Leung^{4

5}, Siobhan Ennis¹, Chanson J Brumme^{2

4}, Julio S G Montaner^{2

4}, Winnie Dong², Natalie Prystajecky^{5

6}, Christopher F Lowe^{3

5}, Mari L DeMarco^{3

5}, Daniel T Holmes^{3

5}, Janet Simons^{3

5}, Masahiro Niikura¹, Marc G Romney^{3

5}, Zabrina L Brumme^{1

2}, Mark A Brockman^{1

2}

Affiliations

¹ Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
² British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada.
³ Division of Medical Microbiology and Virology, St. Paul's Hospital, Vancouver, Canada.
⁴ Department of Medicine, University of British Columbia, Vancouver, Canada.
⁵ Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada.
⁶ British Columbia Centre for Disease Control Public Health Laboratory, Vancouver, Canada.

Abstract

Background: Longer-term immune response data after 3 doses of coronavirus disease 2019 (COVID-19) mRNA vaccine remain limited, particularly among older adults and after Omicron breakthrough infection.

Methods: We quantified wild-type- and Omicron-specific serum immunoglobulin (Ig)G levels, angiotensin-converting enzyme 2 displacement activities, and live virus neutralization up to 6 months after third dose in 116 adults aged 24-98 years who remained COVID-19 naive or experienced their first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during this time.

Results: Among the 78 participants who remained COVID-19 naive throughout follow up, wild-type- and Omicron-BA.1-specific IgG concentrations were comparable between younger and older adults, although BA.1-specific responses were consistently significantly lower than wild-type-specific responses in both groups. Wild-type- and BA.1-specific IgG concentrations declined at similar rates in COVID-19-naive younger and older adults, with median half-lives ranging from 69 to 78 days. Antiviral antibody functions declined substantially over time in COVID-19-naive individuals, particularly in older adults: by 6 months, BA.1-specific neutralization was undetectable in 96% of older adults, versus 56% of younger adults. Severe acute respiratory syndrome coronavirus 2 infection, experienced by 38 participants, boosted IgG levels and neutralization above those induced by vaccination alone. Nevertheless, BA.1-specific neutralization remained significantly lower than wild-type, with BA.5-specific neutralization lower still. Higher Omicron BA.1-specific neutralization 1 month after third dose was an independent correlate of lower SARS-CoV-2 infection risk.

Conclusions: Results underscore the immune benefits of the third COVID-19 mRNA vaccine dose in adults of all ages and identify vaccine-induced Omicron-specific neutralization as a correlate of protective immunity. Systemic antibody responses and functions however, particularly Omicron-specific neutralization, decline rapidly in COVID-19-naive individuals, particularly in older adults, supporting the need for additional booster doses.

Keywords: COVID-19; Omicron; mRNA vaccine; older adults; postvaccination infection.