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Abstract Therapeutic antibodies, due to their high affinity and specificity toward their biological targets, may demonstrate reduced harmful side effects compared with traditional drug moieties. While most of the as‐yet clinically approved antibody therapeutics have targeted extracellular or membrane‐bound domains, the ability to target intracellular antigens with antibodies opens up tremendous opportunities for imaging, diagnosis, and therapeutic applications. Generally, delivery concerns have limited the ability to target intracellular antigens, as many antibodies cannot easily cross the cell membrane due to their size and surface chemistry. Delivery platforms have been explored to address this issue, including physical methods, fusion protein/peptide techniques, and synthetic carrier‐based systems. This review summarizes the progress of carrier‐based intracellular antibody delivery systems employing synthetic lipids, polymers, and inorganic nanomaterials. Antibodies targeting various epitopes have been loaded through adsorption, conjugation, or physical encapsulation strategies. Successful intracellular deliveries have been demonstrated largely through fluorescence imaging using dye‐labeled antibody cargos. Specific synthetic delivery platforms have great potential for ex vivo and in vivo therapeutic applications. Challenges and opportunities are further discussed for material scientists to explore in this research area.
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This content will become publicly available on May 5, 2026
Novel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particles
Summary Immunofocusing on conserved, subdominant epitopes is critical for vaccines against highly diverse viruses such as HIV-1, influenza, and SARS-CoV-2. The eight-residue N-terminus of the HIV-1 fusion peptide (FP) is one such example of a promising yet small target. We developed new FP immunogens using three alphavirus-like particles (VLPs) and introduced additional glycans to mask shared carrier-specific epitopes. In two independent guinea pig studies, sequential immunization with heterologous carriers enhanced FP-directed antibody titers, which were further improved with glycan engineering. Separately, using diverse FP variants sharing the same N-terminal six amino acids increased neutralizing antibody titers. When combined, these two strategies led to higher FP-directed titers and, after Env trimer boosting, induced FP-directed neutralizing antibodies against multi-clade wild-type HIV-1 in nearly all animals. These findings established the importance of minimizing recurrent off-target epitopes across immunizations and support the engineered VLPs as a promising platform for peptide immunization. HighlightsNovel HIV-1 fusion peptide immunogens using glycan-engineered alphavirus-like particlesImproved FP-directed response by minimizing recurrent carrier-specific epitopes across immunizationsImproved neutralizing response by sequential immunization with diverse FP variantsFP-directed antibodies neutralizing multi-clade wildtype viruses in nearly all animals
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- Award ID(s):
- 2400220
- PAR ID:
- 10623852
- Publisher / Repository:
- bioRxiv
- Date Published:
- Format(s):
- Medium: X
- Institution:
- bioRxiv
- Sponsoring Org:
- National Science Foundation
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