P19-07. Development of a protective HIV/SIV vaccine based on a self-boosting cytomegalovirus vector
Bibliographic record
Abstract
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus responsible for asymptomatic, dormant, lifelong infection in healthy individuals. HCMV frequently reactivates inducing a strong, mucosally-oriented immune response. These features of HCMV provide advantages over other viral vectors investigated to date as HIV vaccine candidates. Therefore, we hypothesize that an HCMV-based vaccine can elicit safe and protective HIV-specific immunity in humans. Cytomegaloviruses are highly species-specific viruses and generally restricted in their ability to infect even closely related hosts. Therefore, to test our hypothesis, we propose to use rhesus cytomegalovirus (RhCMV), a non-human primate cytomegalovirus, as a vaccine vector to induce protective immunity to simian immunodeficiency virus (SIV) in cynomolgus macaques (CM). RhCMV is considered the best animal model for HCMV, and SIV pathogenesis in CM closely mimics HIV/AIDS pathogenesis in humans. Phase 1: To determine if CMV sero-positive CM can be re-infected with RhCMV and to evaluate immunogenicity of the vector. Phase 2: Construction of RhCMV expressing codon-optimized SIV antigens gag, pol, env and Nef-Tat-Rev fusion protein, and assess the levels and pattern of SIV antigen expression and growth in vitro . Phase 3: Compare the in vivo growth and immunogenicity of these vectors and their ability to confer protection following a multi-low dose mucosal challenge with pathogenic SIVmac239 in CM. Phase 1: To differentiate RhCMV from endogenous cynomolgus CMV, a recombinant RhCMV expressing green fluorescent protein (RhCMV-EGFP) has been constructed. Six CMV seropositive adult CM were subcutaneously inoculated with live RhCMV-EGFP and two animals were inoculated with UV-inactivated RhCMV-EGFP. Four CM serve as control animals. Currently we are in the process of evaluation of clinical and immunological responses to the vaccine vector (RhCMV) and to EGFP. This RhCMV-based SIV vaccine study will address key issues of the immunogenicity, protective efficacy and self boosting-capacity of this herpesvirus vector.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".