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Self‐Albumin Camouflage of Carrier Protein Prevents Nontarget Antibody Production for Enhanced LDL‐C Immunotherapy
Author(s) -
Ji Haiying,
Wu Guangxi,
Li Yongyong,
Wang Kun,
Xue Xiaomei,
You Shasha,
Wu Shengming,
Ren Tianbin,
He Bin,
Shi Xueyin
Publication year - 2020
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201901203
Subject(s) - keyhole limpet hemocyanin , antibody , antigen , internalization , epitope , peptide , immunology , chemistry , biology , microbiology and biotechnology , biochemistry , receptor
Elevated low‐density lipoprotein cholesterol (LDL‐C) increases the risk of atherosclerotic cardiovascular disease. Peptide‐based PCSK9 vaccines have shown a promising prospect of reducing LDL‐C. In peptide vaccine (pVax) design, the peptide antigens need to conjugate with carrier protein (CP). However, CP incorporation can induce undesirable anti‐CP antibodies, which sterically mask peptide epitopes from being recognized by specific B cells and impair subsequent therapeutically antibody production. This epitopic suppression has posed a barrier in clinical translation of conjugate vaccines all along. A model CP (keyhole limpet hemocyanin, KLH) is herein camouflaged with serum albumin (SA) into hybrid nanocarriers (SA@N), with PCSK9 peptide being anchored onto the surface to form nanovaccine (SA@NVax). Such camouflage of KLH via high “self” SA coverage is able to inhibit KLH from extracellular immune recognition and prevent detectable anti‐KLH antibody production. Furthermore, the nanovaccine around 70 nm stabilized by intermolecular disulfide network is ideal for internalization and biodegradation by antigen presenting cells as well as better retention in draining lymph nodes and spleen. As expected, the SA@NVax efficiently primes higher anti‐PCSK9 IgG antibody titer than PCSK9 pVax.