Membrane Env Liposomes Facilitate Immunization with Multivalent Full-Length HIV Spikes

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• HIV vaccine development aims to generate broadly neutralizing antibodies (bNAbs) targeting the viral envelope glycoprotein spikes (mEnv).
• Current soluble Env (sEnv) vaccines face challenges with stability, antigenicity, and deletion of critical neutralizing epitopes.
• Multivalent membrane-embedded Env (mEnv) vaccines are difficult to produce due to trimer instability and low expression levels.

Purpose of the Study:

• To develop a novel multivalent mEnv vaccine platform for eliciting HIV bNAbs.
• To create a biochemically defined platform using mEnv spikes embedded in liposomes (MELs).
• To assess the immunogenicity and neutralizing capacity of MELs against HIV.

Main Methods:

• Purified and fixed mEnv trimers were incorporated into liposomes using a mild detergent method.
• The resulting membrane Env liposomes (MELs) were characterized for mEnv orientation and particle size (133 nm).
• Rabbits were immunized sequentially with MELs, and elicited antibody responses were analyzed.

Main Results:

• MELs displayed mEnv spikes in the correct orientation and were recognized by HIV bNAbs.
• Immunization with MELs elicited antibodies capable of neutralizing tier 2 HIV isolates.
• Analysis provided insights into improving antibody responses by modifying immunogens, particularly concerning glycosylation sites.

Conclusions:

• MELs represent a stable, biochemically defined platform for rational immunization strategies to elicit HIV bNAbs.
• This platform enables high-valency display of mEnv and may be adaptable for other membrane-bound targets.
• The MEL approach offers a promising avenue for developing effective HIV vaccines.