tetano
Editor, Senior Moderator
Open Forum Infect Dis
. 2023 Feb 9;10(3)
fad073.
doi: 10.1093/ofid/ofad073. eCollection 2023 Mar.
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[SUP] 1 [/SUP], Hope R Lapointe[SUP] 2 [/SUP], Peter K Cheung[SUP] 1 2 [/SUP], Yurou Sang[SUP] 1 [/SUP], Fatima Yaseen[SUP] 1 [/SUP], Rebecca Kalikawe[SUP] 1 [/SUP], Sneha Datwani[SUP] 1 [/SUP], Laura Burns[SUP] 3 [/SUP], Landon Young[SUP] 3 [/SUP], Victor Leung[SUP] 4 5 [/SUP], Siobhan Ennis[SUP] 1 [/SUP], Chanson J Brumme[SUP] 2 4 [/SUP], Julio S G Montaner[SUP] 2 4 [/SUP], Winnie Dong[SUP] 2 [/SUP], Natalie Prystajecky[SUP] 5 6 [/SUP], Christopher F Lowe[SUP] 3 5 [/SUP], Mari L DeMarco[SUP] 3 5 [/SUP], Daniel T Holmes[SUP] 3 5 [/SUP], Janet Simons[SUP] 3 5 [/SUP], Masahiro Niikura[SUP] 1 [/SUP], Marc G Romney[SUP] 3 5 [/SUP], Zabrina L Brumme[SUP] 1 2 [/SUP], Mark A Brockman[SUP] 1 2 [/SUP]
Affiliations
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.
. 2023 Feb 9;10(3)
fad073.doi: 10.1093/ofid/ofad073. eCollection 2023 Mar.
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[SUP] 1 [/SUP], Hope R Lapointe[SUP] 2 [/SUP], Peter K Cheung[SUP] 1 2 [/SUP], Yurou Sang[SUP] 1 [/SUP], Fatima Yaseen[SUP] 1 [/SUP], Rebecca Kalikawe[SUP] 1 [/SUP], Sneha Datwani[SUP] 1 [/SUP], Laura Burns[SUP] 3 [/SUP], Landon Young[SUP] 3 [/SUP], Victor Leung[SUP] 4 5 [/SUP], Siobhan Ennis[SUP] 1 [/SUP], Chanson J Brumme[SUP] 2 4 [/SUP], Julio S G Montaner[SUP] 2 4 [/SUP], Winnie Dong[SUP] 2 [/SUP], Natalie Prystajecky[SUP] 5 6 [/SUP], Christopher F Lowe[SUP] 3 5 [/SUP], Mari L DeMarco[SUP] 3 5 [/SUP], Daniel T Holmes[SUP] 3 5 [/SUP], Janet Simons[SUP] 3 5 [/SUP], Masahiro Niikura[SUP] 1 [/SUP], Marc G Romney[SUP] 3 5 [/SUP], Zabrina L Brumme[SUP] 1 2 [/SUP], Mark A Brockman[SUP] 1 2 [/SUP]
Affiliations
- PMID: 36910697
- PMCID: PMC10003738
- DOI: 10.1093/ofid/ofad073
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.