Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation
Bibliographic record
Abstract
BACKGROUND: Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA. METHODS: Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters. RESULTS: Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination. CONCLUSION: This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT02514018. FUNDING: Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments.
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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".