Liposome-displayed apob fragment for active immunotherapy against atherosclerosis

The National Heart, Lung, and Blood Institute awarded Pop Biotechnologies Inc. $309,794 under the Cardiovascular Diseases Research program (CFDA 93.837) on August 1, 2026, for a Phase I Small Business Innovation Research project to develop a liposome-displayed apolipoprotein B fragment vaccine candidate for active immunotherapy against atherosclerosis.

Pop Biotechnologies will advance a P210 peptide vaccine by combining it with the company's spontaneous nanoliposome antigen particle (SNAP) platform, which uses cobalt porphyrin-phospholipid (COPOP) liposomes to convert histidine-tagged peptides into stabilized ~100 nanometer particles. The SNAP system incorporates monophosphoryl lipid A (3D6A-PHAD, a TLR4 agonist) and QS-21 (an inflammasome activator) as the CPQ adjuvant system to elicit cellular immune responses. The preliminary research hypothesis holds that low-affinity P210-reactive T cell population modulation drives the observed atheroprotective effects in murine atherosclerosis models. Pop Biotechnologies partners with Cedars-Sinai, which pioneered the P210 epitope immunotherapy approach. The work addresses atherosclerotic cardiovascular disease, which remains the leading cause of mortality in the United States despite lipid-lowering therapeutics.

The award period runs from August 1, 2026 through July 31, 2027. Work is performed in Amherst, New York.

Abstract

Although lipid-lowering therapeutics like statins offer benefit, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality in the US. ASCVD is primarily a chronic, immune-mediated inflammatory disease, therefore immune modulating treatments hold potential to rationally address the underlying cause. Low- density lipoprotein (LDL) and its apolipoprotein B-100 (APOB-100) scaffold are central to ASCVD disease pathology, making these key targets for novel immune modulating therapies. Our group at cedars-sinai pioneered ASCVD active immunotherapy focused on the P210 epitope, which is derived from APOB-100. Our extensive immunization screening of pools of APOB peptides identified the synthetic P210 peptide which could reproducibly confer atheroprotective effects in murine atherosclerosis models. To advance a P210 vaccine, we will partner with POP biotechnologies (POP BIO), who is commercializing an active immunotherapy platform based on their spontaneous nanoliposome antigen particle (SNAP) vaccine system. SNAP is enabled by cobalt porphyrin-phospholipid (COPOP) liposomes, which convert histidine-tagged short peptide antigens into ~100 NM biostable particles by simple admixture. COPOP liposomes incorporate synthetic monophosphoryl lipid a (3D6A-phad; a TLR4 agonist) and QS-21 (an inflammasome activator), to form the CPQ adjuvant system that elicits ultrapotent cellular responses. The CPQ adjuvant system has demonstrated that short MHC class-I peptides induce high frequency antigen-specific CD8+ T cells. P210 is a not a strong binder for most murine or human MHC-I alleles, which provides our current working hypothesis that low affinity P210-reactive T cell population modulation is responsible for the observed efficacy. In a major advance for our research our preliminary data has shown that CPQ system can be combined with P210 to elicit P210-specific CD8+ T cells, thereby providing a premise for the proposed studies. To advance P210-SNAP towards eventual clinical testing we will carry out the following aims: specific aim 1: formulate P210-SNAP peptide vaccines and assess immunogenicty: we will evaluate multiple SNAP vaccine formulations to determine the most effective approach for inducing P210-specific CD8+ T-cell responses. Specific aim 2. Validate the translational potential of P210- SNAP in our humanized A2KB-TG apoe-/- transgenic mouse model: the optimized vaccine will be tested in hypercholesterolemic transgene mice on apoe-/- background carrying human HLA-A0201 (named A2KB-TG apoe-/- mice) to assess its ability to reduce atherosclerosis. Outcomes will include reductions in lesion size and markers of plaque phenotypes. The translational potential will be assessed by testing the vaccine in young mice for atherosclerosis progression and aged and high-FAT diet-induced models that reflect clinical disease scenarios. We will further probe mechanistic aspects of protection by correlating HLA-A2, P210-specific CD8+ T cell frequency with disease burden. We will also collect P210-cross-reactive specific CD8+ T cells and carry out T cell receptor sequencing to characterize T cell repertoire changes.