Impact of the expression system on the immune responses to self-assembling protein nanoparticles (SAPNs) displaying HIV-1 V1V2 loop

Abstract

The V1V2 loop of the Env protein is a major target for HIV-1 vaccine development because in multiple studies antibodies to this region correlated with protection. Although SAPNs expressed in E. coli elicited anti-V1V2 antibodies, the Env protein is heavily glycosylated. In this study the technology has been adapted for expression in mammalian cells. SAPNs containing a V1V2 loop from a B-subtype transmitter/founder virus were expressed in E. coli, ExpiCHO, and Expi293 cells. Independent of the expression host, particles were well-formed. All SAPNs raised high titers of V1V2-specific antibodies, however, SAPNE.coli induced a mainly anti-V1 response, while SAPNExpiCHO and SAPNExpi293 induced a predominantly anti-V2 response. In an ADCP assay, sera from animals immunized with the SAPNExpiCHO or SAPNExpi293 induced a significant increase in phagocytic activity. This novel way of producing SAPNs displaying glycosylated epitopes could increase the antibody titer, functional activity, and shift the immune response towards the desired pathway.