Cao Han, Wang Yunfei, Luan Ning, Liu Cunbao
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.
Vaccines (Basel). 2021 Mar 25;9(4):310. doi: 10.3390/vaccines9040310.
Theoretically, the subunit herpes zoster vaccine Shingrix could be used as a varicella vaccine that avoids the risk of developing shingles from vaccination, but bedside mixing strategies and the limited supply of the adjuvant component QS21 have made its application economically impracticable. With lipid nanoparticles (LNPs) that were approved by the FDA as vectors for severe acute respiratory syndrome coronavirus 2 vaccines, we designed a series of vaccines efficiently encapsulated with varicella-zoster virus glycoprotein E (VZV-gE) and nucleic acids including polyinosinic-polycytidylic acid (Poly I:C) and the natural phosphodiester CpG oligodeoxynucleotide (CpG ODN), which was approved by the FDA as an immunostimulator in a hepatitis B vaccine. Preclinical trial in mice showed that these LNP vaccines could induce VZV-gE IgG titers more than 16 times those induced by an alum adjuvant, and immunized serum could block in vitro infection completely at a dilution of 1:80, which indicated potential as a varicella vaccine. The magnitude of the cell-mediated immunity induced was generally more than 10 times that induced by the alum adjuvant, indicating potential as a zoster vaccine. These results showed that immunostimulatory nucleic acids together with LNPs have promise as safe and economical varicella and zoster vaccine candidates.
理论上，亚单位带状疱疹疫苗欣安立适可作为水痘疫苗使用，从而避免接种疫苗引发带状疱疹的风险，但床边混合策略以及佐剂成分QS21的供应有限，使得其应用在经济上不切实际。利用已获美国食品药品监督管理局（FDA）批准作为严重急性呼吸综合征冠状病毒2疫苗载体的脂质纳米颗粒（LNP），我们设计了一系列疫苗，这些疫苗能有效地包裹水痘-带状疱疹病毒糖蛋白E（VZV-gE）以及包括聚肌苷酸-聚胞苷酸（Poly I:C）和天然磷酸二酯CpG寡脱氧核苷酸（CpG ODN）在内的核酸，其中CpG ODN已获FDA批准作为乙肝疫苗中的免疫刺激剂。小鼠的临床前试验表明，这些LNP疫苗诱导产生的VZV-gE IgG滴度比铝佐剂诱导产生的滴度高16倍以上，且免疫血清在1:80稀释度下能完全阻断体外感染，这表明其有作为水痘疫苗的潜力。所诱导的细胞介导免疫强度通常比铝佐剂诱导产生的强度高10倍以上，表明其有作为带状疱疹疫苗的潜力。这些结果表明，免疫刺激核酸与LNP有望成为安全且经济的水痘和带状疱疹候选疫苗。
