Impact of age and SARS-CoV-2 breakthrough infection on humoral immune responses after three doses of COVID-19 mRNA vaccine
- DOI
- Language of the publication
- English
- Date
- 2022-10-04
- Type
- Submitted manuscript
- Author(s)
- Mwimanzi, Francis
- Lapointe, Hope R.
- 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.
- Publisher
- medRxiv
Abstract
Background Longer-term immune response data after three doses of COVID-19 mRNA vaccine remain limited, particularly among older adults and following Omicron breakthrough infection. Methods We quantified wild-type- and Omicron-specific serum IgG levels, ACE2 displacement activities and live virus neutralization up to six months post-third dose in 116 adults aged 24-98 years who remained COVID-19-naïve or experienced their first SARS-CoV-2 infection during this time. Results Among 78 participants who remained COVID-19-naïve throughout follow-up, wild-type- and Omicron BA.1-specific IgG concentrations were comparable between younger and older adults, though 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 among COVID-19-naïve younger and older adults, with median half-lives ranging from 69-78 days. Antiviral antibody function declined substantially over time in COVID-19-naïve individuals, particularly older adults: by six months, BA.1-specific neutralization was undetectable in 96% of older adults, versus 56% of younger adults. SARS-CoV-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. Conclusions Our findings underscore the immune benefits of third COVID-19 mRNA vaccine doses in adults of all ages, but rapid decline of Omicron-specific neutralization activity in COVID-19-naïve individuals, particularly among older adults, demonstrates the need for fourth doses within 3-6 months to maintain systemic responses. Individuals who experienced SARS-CoV-2 breakthrough infection post-third vaccine dose however can likely delay a fourth dose beyond this timeframe.
Subject
- Health,
- Immunization,
- Coronavirus diseases
Rights
Pagination
1-30
Peer review
No
Sponsors
This work was supported by the Public Health Agency of Canada through a COVID-19 Immunology Task Force COVID-19 "Hot Spots" Award (2020-HQ-000120 to MGR, ZLB, MAB). Additional funding was received from the Canadian Institutes for Health Research (GA2-177713 and the Coronavirus Variants Rapid Response Network (FRN-175622) to MAB), the Canada Foundation for Innovation through Exceptional Opportunities Fund COVID-19 awards (to MAB, MD, MN, 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.
Relation
- Is replaced by:
- https://doi.org/10.1093/ofid/ofad073