Background: Dose-sparing approaches can be effective in maintaining immunogenicity and safety while expanding vaccine coverage. We previously demonstrated that a half dose of ChAdOx1 nCoV-19 is as effective and immunogenic for primary vaccination. Methods: This non-inferiority, non-randomized controlled trial evaluated the effectiveness, humoral, and cellular immune responses of a third booster dose—comparing half-dose and full-dose regimens—in individuals aged 18–49 years, with a 1-year follow-up. Results: A total of 2801 participants were enrolled: 2352 received half doses and 449 received full doses. The incidence rate of COVID-19 was 225.0 per 1000 person-years in the half-dose group and 173.8 in the full-dose group, with no significant difference in effectiveness (β = −0.05; 95% CrI: −0.24 to 0.15). No deaths occurred, and hospitalization rates were similar. In a subsample (n = 558), anti-S IgG levels peaked 28 days post-dose and declined by day 180 after the primary series [175 (121–252) vs. 121 (71–208) GMT, p < 0.001], but remained elevated after the booster [192.1 (124–297) vs. 550 (380–797) GMT, p < 0.001]. Booster antibody levels were similar between groups [592.4 (318–1140) vs. 550 (380–797) GMT]. The half-dose group showed high titers against Omicron and robust T/B-cell responses (e.g., EMCD4, EMCD8, IFN⁺CD4⁺, CD19⁺TNF⁺). Conclusions: Fractional half dose of ChAdOx nCov-19 was effective and non-inferior to a full booster dose. Homologous regimen with 3 half doses or 3 full doses induced a similar increase in antibody titers and robust cellular response. ClinicalTrials.gov (NCT05059106).

The present study aimed to evaluate the kinetics of the phenotypic profile and integrative networks of T/B-cells in severe COVID-19 patients, categorized according to disease outcome, during the circulation of the B.1.1.28 and B.1.1.33 SARS-CoV-2 strains in Brazil. Peripheral blood obtained at distinct time points (baseline/D0; D7; D14-28) was used for ex vivo flow cytometry immunophenotyping. The data demonstrated a decrease at D0 in the frequency of CD3⁺ T-cells and CD4⁺ T-cells and an increase in B-cells with mixed activation/exhaustion profiles. Higher changes in B-cell and CD4⁺ T-cells at D7 were associated with discharge/death outcomes, respectively. Regardless of the lower T/B-cell connectivity at D0, distinct profiles from D7/D14-28 revealed that, while discharge was associated with increasing connectivity for B-cells, CD4⁺ and CD8⁺ T-cells death was related to increased connectivity involving B-cells, but with lower connections mediated by CD4⁺ T-cells. The CD4⁺CD38⁺ and CD8⁺CD69⁺ subsets accurately classified COVID-19 vs. healthy controls throughout the kinetic analysis. Binary logistic regression identified CD4⁺CD107a⁺, CD4⁺T-bet⁺, CD8⁺CD69⁺, and CD8⁺T-bet⁺ at D0 and CD4⁺CD45RO⁺CD27⁺ at D7 as subsets associated with disease outcomes. Results showed that distinct phenotypic timeline kinetics and integrative networks of T/B-cells are associated with COVID-19 outcomes that may subsidize the establishment of applicable biomarkers for clinical/therapeutic monitoring.