A Trial to Evaluate an HIV Envelope Trimer, N332-GT5 gp140, Adjuvanted With SMNP in Adult Participants Without HIV

Description

This study will evaluate the safety and immunogenicity of combining 2 FIH products: N332-GT5 gp140 HIV trimer protein adjuvanted with SMNP, co-administered as 2 bolus immunizations (week 0 and 8) or fractionated escalating dose prime (6 immunizations over 3 weeks) followed by bolus immunization boost (week 10), via either subcutaneous (SC) route in the upper arm or intramuscular (IM) route to the deltoid. N332-GT5 gp140 is based on the BG505 MD39 native-like trimer (NLT). The dose escalation study (Part A) will determine the maximum safe dose, within our schema, of N332-GT5 gp140 and SMNP for 4 vaccination modalities: IM/bolus, IM/fractionated escalating dose prime, SC/bolus, and SC/fractionated escalating dose prime. A primary endpoint will be safety and tolerability. The trial will evaluate: (1) the concept of generalized germline targeting for HCDR3-dominant bnAb precursors; (2) germline targeting for V3-glycan (V3G)-specific BG18-class bnAbs; (3) establishing a safe and effective dose of SMNP in humans; (4) immunogenicity of an HIV Env trimer adjuvanted with SMNP; and (5) ranking of HIV trimer immune response magnitude and quality for bolus/IM, bolus/SC, and fractionated escalating dose with one of either IM or SC.