03 SARS-cov-2 Infection improves the broadness and persistence of adaptive immunity in vaccinated immunosuppressed children
Bibliographic record
Abstract
Abstract Background Immunosuppressed (IS) children show increased vulnerability to infections including SARS-CoV-2. Therefore, it is necessary to better understand correlates of protection in that particularly vulnerable population to avoid critical illness due to COVID-19. Objectives The objective was to determine whether the three-doses primary vaccination regimen is sufficient for immunosuppressed children to develop comparable immunity as healthy children after two doses of vaccine. Design/Methods To interrogate the impact of vaccination of IS children, we compared a cohort of healthy children (n=52) receiving the standard two-doses regimen to children affected by primary (PID) or secondary humoral immune deficiencies (n=30) who received two or three vaccine doses. In the secondary antibody deficiency (SAD) group (n=14), 11 children were treated with rituximab and three had persistent hypogammaglobulinemia after stem cell transplantation or treatment with CAR T cell therapy. IgG, IgA, and IgM binding the spike protein, its receptor-binding-domain, and nucleocapsid were measured in serum and saliva. Neutralizing antibody titers (nAbs) were determined via live-SARS-CoV-2 micro-neutralizations. Cell-mediated immunity was quantified by assessing interferon-gamma secretion using ELISpot. Results After the second vaccine dose, IS children showed reduced circulating binding and nAbs compared to their healthy counterparts. While all healthy children had nAbs after two doses, only 27% of IS children did. Importantly, the third dose significantly increased nAb titers in PID children to levels comparable to healthy children (median nAb titers of 101 [32-403] in PID after three doses compared to 101 [32-254] in healthy children after two doses), but this finding did not last over time, since PID children had much lower antibody levels in the long term. In contrast, children with SAD did not develop nAb following vaccination. Interestingly, breakthrough (BT) infection induced a profound increase in nAbs in all children, including in children with SAD. Indeed, 80% of infected SAD children developed nAbs after SARS-CoV-2 infection. Functional T cell immunity seemed sufficient to protect against symptomatic disease and complications in children without nAb. Conclusion Three intramuscular vaccine doses are not sufficient for immunosuppressed children to develop potent and persistent immunity against SARS-CoV-2. As BT infection mimics mucosal challenge, these results support the idea that mucosal vaccination strategies could improve immune responses in IS children.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".