Synthetic melanin bound to subunit vaccine antigens significantly enhances CD8+ T-cell responses

Cytotoxic T-lymphocytes (CTLs) play a key role in immunity against cancer; however, the induction of CTL responses with currently available vaccines remains difficult. Because several reports have suggested that pigmentation and immunity might be functionally linked, we investigated whether melanin can act as an adjuvant in vaccines. Short synthetic peptides (8–35 amino acids long) containing T-cell epitopes were mixed with a solution of L-Dopa, a precursor of melanin. The mixture was then oxidized to generate nanoparticles of melanin-bound peptides. Immunization with melanin-bound peptides efficiently triggered CTL responses in mice, even against self-antigens and at a very low dose of peptides (microgram range). Immunization against a tumor antigen inhibited the growth of established tumors in mice, an effect that was abrogated by the depletion of CD8+ lymphocytes. These results demonstrate the efficacy of melanin as a vaccine adjuvant.

细胞毒性T淋巴细胞（Cytotoxic T-lymphocytes, CTLs）在抗肿瘤免疫中发挥关键作用，但当前现有疫苗诱导CTL应答仍颇具难度。鉴于多项研究提示色素沉着与免疫功能可能存在功能性关联，本研究探讨了黑色素（melanin）能否作为疫苗佐剂。将携带T细胞表位（T-cell epitopes）的短合成肽（长度8~35个氨基酸）与黑色素前体左旋多巴（L-Dopa）溶液混合，经氧化反应后制备得到黑色素结合肽纳米颗粒。以该黑色素结合肽免疫小鼠，可高效诱导CTL应答，即便针对自身抗原且肽给药剂量低至微克级时亦有效。针对肿瘤抗原的免疫接种可抑制小鼠体内已定植肿瘤的生长，该效应可通过清除CD8+淋巴细胞而被阻断。上述结果证实了黑色素作为疫苗佐剂的有效性。