Third dose of ChAdOx1 nCoV-19 vaccine and prolonged second dose-intervals are both associated with increased antibody titers

1. An interval of 44-45 weeks between the first and second dose resulted in a four-fold increase in median antibody titers, 28-days after administration, compared to the standard interval of 8-12 weeks.

2. A two-fold increase in median IgG levels was observed among patients 28-days after receiving their third dose compared to 28-days after the second.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The optimal interval of time between the first and second dose of COVID-19 vaccines has been a subject of debate. In addition, while countries facing supply shortages consider the impact of extending the dosing interval, those with a surplus mull over the possibility of a third booster dose. So far, little research has been done to assess the impact of either regimen on SARS-CoV-2 immunogenicity. This sub study of two randomized controlled trials aimed to assess the efficacy of a prolonged second dose of ChAdOx1 nCoV-19, compared to the regular 8-12-week interval. This study also sought to identify the response to a third dose given to patients 28-38 weeks after the second dose. The outcomes measured in this study were IgG-antibody titers levels 28-days after receipt of a second or third dose of ChAdOx1 nCoV-19. According to study results, an increase in immunogenicity was reported among patients with a prolonged second dose interval and among those who received an additional third dose. This study was limited by a small sample size and a single maker of the COVID-19 vaccine. Given the heterogeneity of vaccine accessibility across the world, future studies on other COVID-19 vaccines would be beneficial in informing public health decisions.

Click to read the study in The Lancet

Relevant Reading: Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant

In-depth [randomized controlled trial]: From Mar 11 to Mar 21, 2021, 90 patients were enrolled for a third ChAdOx1 nCoV-19 booster-dose in Oxford, UK. Additionally, of the 1110 patients who had received their first vaccination dose (previous studies), 321 were included in the analysis (267 with first and second-dose interval of 8-12 weeks, 24 with interval of 15-25 weeks, and 30 with an interval of 44-45 weeks) for comparison of delayed second-dose intervals. For each cohort, antibody titers were measured 28-days following the administration of a second or third vaccine. Included patients were those aged 18-55 years old with single or double doses of the ChAdOx1 nCoV-19 vaccination. The majority (>90%) of patients were White and median age, across cohort, ranged from 32-40 years old.

A prolonged interval between first and second doses was correlated with higher median antibody titers compared to a shorter interval (3738 EUs, interquartile range [IQR] 1824-6625] for 44-45 weeks vs. 1860 EUs [IQR 917-4934] for 15-25 weeks vs. 923 EUs [IQR 525-1764] for 8-12 weeks). A statistically significant difference was observed in IgG titers at 28 days after the third dose compared to 28-days after the second dose (3746 EUs, IQR 2047-6420 for third dose vs. 1792 EUs, IQR 899-4634, Wilcoxon signed rank test p=0.0043). Moreover, T-cell response also increased following the administration of a third dose (200 spot-forming units [SFUs] to 399 SFUs per million peripheral blood mononuclear cells [PBMCs], p=0.012). Findings from this study suggest that both an extended first to second dose interval and addition of a third dose provide increased immunogenicity against COVID-19.

Image: PD 

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