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

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

doi:https://open-science.canada.ca/handle/123456789/3424

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

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dc.contributor.author: Mwimanzi, Francis; Cheung, Peter K.; Sang, Yurou; Yaseen, Fatima; Kalikawe, Rebecca; Datwani, Sneha; Burns, Laura; Young, Landon; Leung, Victor; Ennis, Siobhan; Brumme, Chanson J.; Montaner, Julio S. G.; Dong, Winnie; Prystajecky, Natalie; Lowe, Christopher F.; DeMarco, Mari L.; Holmes, Daniel T.; Simons, Janet; Niikura, Masahiro; Romney, Marc G.; Brumme, Zabrina L.; Brockman, Mark A.; Brockman, Mark A.
dc.date.accessioned: 2025-02-11T15:11:31Z
dc.date.available: 2025-02-11T15:11:31Z
dc.date.issued: 2023-02-09
dc.description.abstract - en: 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.
dc.description.sponsorship: This work was supported by the Public Health Agency of Canada through an award from the COVID-19 Immunology Task Force COVID-19 (2020-HQ-000120; to MGR, ZLB, and MAB). Additional funding was received from the Canadian Institutes for Health Research (GA2-177713 and Coronavirus Variants Rapid Response Network FRN-175622; to MAB) and the Canada Foundation for Innovation through Exceptional Opportunities Fund – COVID-19 awards (to MAB, MD, MN, and ZLB). FM is supported by a fellowship from the CIHR Canadian HIV Trials Network. FY was supported by an SFU Undergraduate Research Award. MLD and ZLB hold Scholar Awards from the Michael Smith Foundation for Health Research.
dc.identifier.doi: https://doi.org/10.1093/ofid/ofad073
dc.identifier.issn: 2328-8957
dc.identifier.pubmedID: 36910697
dc.identifier.uri: https://open-science.canada.ca/handle/123456789/3424
dc.language.iso: en
dc.publisher - en: Oxford University Press on behalf of Infectious Diseases Society of America
dc.relation.replaces: https://open-science.canada.ca/handle/123456789/3421
dc.rights - en: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.rights - fr: Creative Commons Attribution - Pas d'utilisation commerciale - Pas de modification 4.0 International (CC BY-NC-ND 4.0)
dc.rights.uri - en: https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.uri - fr: https://creativecommons.org/licenses/by-nc-nd/4.0/deed.fr
dc.subject - en: Health; Coronavirus diseases; Immunization
dc.subject - fr: Santé; Maladie à coronavirus; Immunisation
dc.subject.en - en: Health; Coronavirus diseases; Immunization
dc.subject.fr - fr: Santé; Maladie à coronavirus; Immunisation
dc.title - en: 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
dc.type - en: Article
dc.type - fr: Article
local.article.journalissue: 3
local.article.journaltitle - en: Open Forum Infectious Diseases
local.article.journalvolume: 10
local.pagination: 1-11
local.peerreview - en: Yes
local.peerreview - fr: Oui

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