COMMENTARY The failed HIV Merck vaccine study: a step back
Bibliographic record
Abstract
or a launching point for future vaccine development? Rafick-Pierre Sekaly The world of human immunodeficiency virus (HIV) vaccines has suffered a baffling setback. The first trial of a vaccine designed to elicit strong cellular immunity has shown no protection against infection. More alarmingly, the vaccine appeared to increase the rate of HIV infection in individuals with prior immunity against the adenovirus vector used in the vaccine. A new study in this issue suggests that a different vaccine approach — using a DNA prime/poxvirus boost strategy — induces polyfunctional immune responses to an HIV immunogen. The disappointing results of the recent vaccine trial suggest that a more thorough assessment of vaccine-induced immune responses is urgently needed, and that more emphasis should be placed on primate models before efficacy trials are undertaken. The pathway to an HIV vaccine has never been considered easy or straightforward ( 1, 2). The challenges involved in developing a successful vaccine have accumulated from the time of the first clinical trials of the Microgenesis vaccine to the highly publicized Vaxgen trial ( 1, 3, 4). These HIV envelope – based vaccines were aimed at inducing neutralizing antibody responses, as several groups had shown that passive transfer of large amounts of neutral izing antibodies could protect primates against infection. Unfortunately, these first trials failed in large part because inducing neutralizing antibodies is a daunting task at which more than one group has failed ( 5). Other reasons for these failures include the genetic variability of the viral envelope proteins, which allows the virus to escape neutralizing antibodies, and the difficulty in identifying immunogens and immunization platforms that consistently induce antibodies that can neutralize several HIV clades ( 6). A shift in focus In light of the difficulties in eliciting neutralizing antibodies, the field has R.-P. Sekaly is at Universit é de Montr é al, CR-CHUM, Institut National de la Sant é et de la Recherche M é dicale U743, Montr é al, Qu é bec H2X1P1, Canada.
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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 | 0.015 | 0.069 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.003 | 0.005 |
| Scholarly communication | 0.004 | 0.007 |
| Open science | 0.008 | 0.002 |
| Research integrity | 0.039 | 0.046 |
| Insufficient payload (model declined to judge) | 0.014 | 0.012 |
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".