HIV-Specific T Cells: Strategies for Fighting a Moving Target
Bibliographic record
Abstract
HIV vaccine development faces many hurdles, including the failure of empirical approaches, an incomplete understanding of protective immunity, and the extreme genetic diversity of HIV-1. HIV is a moving target in at least two key ways: 1) within an infected individual, years of evolution lead to the formation of quasispecies, and selection of variants with increased fitness, and 2) during the course of the pandemic, subtypes change in frequency as they are transmitted from host to host. In spite of this, CD8+ T cells are often able to overcome HIV diversity, leading to relatively high levels of cross-reactive and cross-clade responses. Recent research suggests that the cross-reactivity of HIV-specific CD8+ T cell responses should be evaluated comprehensively, using multiple immunological assays (including those that correlate best with protective immunity), and taking into account subtle differences in epitopic variation, presenting HLA allele, and cognate TCR that all influence recognition and escape. In addition, although escape and cross-reactivity are often predictable, important differences can be present, particularly in the setting of multiple and different clades. Finally, strategies to optimize the induction of protective, cross-reactive T cells, and towards the likely infecting strain in the mucosa where exposure occurs and opportunities to prevent infection are greatest, are urgently needed. Though some cues can be found from observational studies, more in depth analyses of past and ongoing HIV vaccine trials will be needed to know if and how HIV genetic diversity can be overcome by vaccine-induced T cells. Keywords: HIV, vaccine, clade, cell-mediated immunity, pandemic, immunological assays, cross-reactive T cells, vaccine-induced T cells, autologous neutralizing antibodies, malaria, highly exposed seronegative (HESN), SIV vaccination, long-term non-progressors (LTNPs), elite controllers (ECs), HIV diversity, influenza epidemic, Phylogenetic analyses, viral replication, TCR recognition, HIV-specific CD8+ T cell responses, recombinant vaccinia cross-clade screen, protective immunity, viremia, infected placebo recipients, phylogenetic clusters, cross-clade epitopes, IFN, Chromium, Leishmania major, yellow fever, ELISAs, TCR clonotype, immunogenicity, Antagonism, cytokine, cytotoxicity, autoimmune diseases, immune system, HIV vaccination, HIV vaccine, sexually transmitted infections, CMV-vectored vaccine
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.003 | 0.005 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.004 | 0.007 |
| Insufficient payload (model declined to judge) | 0.009 | 0.004 |
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".