Membrane Env liposomes for immunization with HIV spikes

A key goal in HIV vaccine design remains to elicit broadly neutralizing antibodies (bnAbs) against the membrane-embedded envelope glycoprotein spike (mEnv). However, mEnv has lagged behind engineered soluble Envs in vaccine development due to low expression yields and the presence of extraneous proteins on particles. Here, we describe a mEnv vaccine platform that requires no extra proteins or protein engineering. MEnv trimers were fixed, purified and combined with liposomes in mild detergent. On removal of detergent, mEnvs were observed embedded in particles, designated mE nv l iposomes (MELs), which were recognized by HIV bnAbs but not non-nAbs. Following sequential immunization in rabbits, MEL antisera neutralized select tier 2 HIV isolates. Variations between the Env immunogens, including a missing N-glycosylation site at position 197 near the CD4 binding site, provide insights into the specificities elicited and possible ways to improve immunogens. MELs can facilitate vaccine design to elicit HIV bnAbs using biochemically defined and multimerized mEnv.