However, how these measurements relate to antibody levels and durations of protection in populations over time, and after BNT162b2 vaccination, is not fully understood. Similarly for the mRNA-1273 vaccine, anti-spike antibody and neutralization titers were inversely associated with SARS-CoV-2 infection, with 68.5% of vaccine efficacy up to 126 days after the second dose mediated by day 29 neutralization titers 15. However, large population-based investigations of how these different dosing intervals, or other factors, affect longer-term antibody changes after the second dose are limited, but they are essential to assess the duration of protection and the need for booster doses.Īfter the ChAdOx1 vaccine, anti-spike IgG and pseudovirus neutralization titers are associated with protection against symptomatic SARS-CoV-2 infection 14. With the rapid emergence of the Delta variant, and greater protection after second than first vaccine doses 10, 11, 12, from mid-2021 dosing intervals were reduced to 8 weeks 13 to achieve greater protection faster. However, these studies were based on relatively small sample sizes ( n < 600) or specific population groups such as healthcare workers, potentially reducing generalizability, and antibody levels were measured only at specific times after second doses. Subsequent UK studies showed that extended BNT162b2 dosing intervals generated higher antibody responses than the 3-week interval 7, 8, 9. Response peak unibox trial#Although the ChAdOx1 trial found higher vaccine efficacy with dosing intervals of at least 6 weeks 6, BNT162b2 trials did not compare different dosing intervals. With widespread Alpha variant transmission, in January 2021 the UK government extended the dosing interval from 3–4 weeks to 12 weeks for all vaccines to maximize first dose coverage, based on preliminary data showing high short-term efficacy from single BNT162b2 (90%) and ChAdOx1 (70%) doses 5. Up to 4 October 2021, 85% and 78% of the population (aged ≥12 years) have received one and two doses, respectively 4. In the UK, vaccines were initially prioritized to older adults, frontline health and social care workers, and clinically vulnerable individuals, and then offered to other adults in decreasing age order 3. The Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1 nCoV-19 (hereafter ChAdOx1) SARS-CoV-2 vaccines have been widely used in the United Kingdom (UK) and worldwide 1, 2. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable. At least 67% protection against infection was estimated to last for 2–3 months after two ChAdOx1 doses, for 5–8 months after two BNT162b2 doses in those without prior infection and for 1–2 years for those unvaccinated after natural infection. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. Prior infection significantly increased antibody peak level and half-life with both vaccines. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination.
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