Phase I HIV vaccine trial with DNAALVAC-HIV gp120 delta V1 vaccines

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

The project will exploit the DNA/ALVAC-HIV vaccine platform's ability to induce lasting trained monocyte memory in combination with a clade AE (A244 strain) V1-deleted HIV-gp160 prime and a novel V1-deleted HIV gp120/alum protein boost. The deletion of V1 from the gp120 envelope will be specially engineered to minimize antibody interference and elicit a high level of antibodies to V2, the primary correlate of risk in RV144. Alum hydroxide will be used as adjuvant for its ability to maximize the induction of trained immunity (through its ability to induce IL-1B) and CD4+ T-cell responses that constituted the secondary correlate of decreased risk of HIV acquisition in RV144. The overall objective of this proposal is to design and produce both a novel HIV V1-deleted A244 gp160 (A244 DeltaV1 gp160) DNA vaccine and a novel HIV V1-deleted A244 gp120 (A244 DeltaV1 gp120) in GMP conditions for testing in a phase I human HIV vaccine trial. These immunogens will first be tested in macaques to assess whether this approach also induces long-lasting, non-interfering antibodies, innate monocyte memory, and adaptive CD4+ T-cells with a low inflammatory profile in humans. The investigation of protective monocyte, or NK memory trained immunity, will prove beneficial in combatting additional infectious diseases and cancer. Evolutionary conserved from invertebrates, trained immunity is an ancient trait of the human immune system that is defined by durable epigenetic reprogramming of monocytes, providing the first line of defense against pathogens .This will lead not only to the production and testing of a novel HIV vaccine, but also to the thorough investigation of unexplored host protective immune responses in non-human primates (NHP) whose immune system mirrors that of humans.