Investigating vaccine uptake dynamics of neutrophils using HIV-1 Envelope glycoprotein trimer

Abstract

ABSTRACTRhesus macaques were previously immunized with two distinct subunit vaccine candidates, to monitor antigen trafficking by immune cells infiltrating the site of injection. The first, a formulation based on the HIV-1 envelope glycoprotein (Env) and the other based on the RSV-fusion (F) protein. Neutrophil and monocyte uptake profiles were vastly different between the vaccine candidates despite similar cell infiltration numbers, hinting that antigen characteristics could orchestrate different innate responses. Notably, the Env trimer is significantly more glycosylated than RSV-F.Recapitulating thesein vivoobservations under reliablein vitroconditions is thus of importance in exploring uptake dynamics and insights into the manipulation of innate responses. The study later demonstrated a complement component, Mannose Binding Lectin (MBL), to be resistant to heat-inactivation and binds Env in a CRDdependent manner. Interestingly, the data suggests a heat-labile component of the serum hinders MBL from binding to Env, which corresponded to a weaker uptake profile. Also, the generation of 3 differentially glycosylated Env variants to study glycan-mediated uptake by neutrophils derived contrary observations. In all, modulation of MBL interactions could potentially target specific innate immune cells, particularly neutrophils, and the later development of adaptive immune responses after immunization.