This is a phase 1 first-in-human clinical trial to assess the safety, tolerability, and immunogenicity of eOD-GT8 60mer Vaccine, Adjuvanted, in up to 48 healthy adult HIV-negative volunteers.
The study is a randomized, double-blind, placebo-controlled dosage-escalation Phase 1 study intended to evaluate the safety and immunogenicity of the eOD-GT8 60mer Vaccine, Adjuvanted in a prime-boost regimen.
Science published a research article on December 2, 2022, discussing the results of the phase 1 clinical trial.
Each participant received two administrations of a placebo, a low-dose vaccine, or a high-dose vaccine 8 weeks apart. The eOD-GT8 immunogen was designed to activate B cell precursors for HIV VRC01-class bnAbs defined by their usage of heavy chain variable gene alleles VH1-2*02 or *04 and any light chain complementarity determining region 3 with a length of five amino acids. We collected immune cells from participants' blood and lymph nodes and carried out epitope-specific B cell sorting, B cell receptor (BCR) sequencing, and bioinformatic and statistical analyses.
We also produced monoclonal antibodies and measured their binding affinities for the vaccine antigen. The vaccine had a favorable safety profile and induced VRC01-class responses in 97% (35 of 36) of vaccine recipients, with median frequencies reaching 0.1% among immunoglobulin G memory B cells in the blood. bnAb-precursors shared multiple properties with bnAbs and made substantial gains in somatic hypermutation and affinity with the boost.
The results establish clinical proof of concept for the germline-targeting vaccine design priming strategy, support the development of boosting regimens to generate VRC01-class bnAb responses against HIV, and encourage the application of the germline-targeting strategy to other targets in HIV and other pathogens.