Tan Mei Peng, Tan Wen Siang, Mohamed Alitheen Noorjahan Banu, Yap Wei Boon
Department of Cell and Molecular Biology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.
Center for Toxicology and Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia.
Vaccines (Basel). 2021 Jul 4;9(7):739. doi: 10.3390/vaccines9070739.
Discovery of conserved antigens for universal influenza vaccines warrants solutions to a number of concerns pertinent to the currently licensed influenza vaccines, such as annual reformulation and mismatching with the circulating subtypes. The latter causes low vaccine efficacies, and hence leads to severe disease complications and high hospitalization rates among susceptible and immunocompromised individuals. A universal influenza vaccine ensures cross-protection against all influenza subtypes due to the presence of conserved epitopes that are found in the majority of, if not all, influenza types and subtypes, e.g., influenza matrix protein 2 ectodomain (M2e) and nucleoprotein (NP). Despite its relatively low immunogenicity, influenza M2e has been proven to induce humoral responses in human recipients. Influenza NP, on the other hand, promotes remarkable anti-influenza T-cell responses. Additionally, NP subunits are able to assemble into particles which can be further exploited as an adjuvant carrier for M2e peptide. Practically, the T-cell immunodominance of NP can be transferred to M2e when it is fused and expressed as a chimeric protein in heterologous hosts such as without compromising the antigenicity. Given the ability of NP-M2e fusion protein in inducing cross-protective anti-influenza cell-mediated and humoral immunity, its potential as a universal influenza vaccine is therefore worth further exploration.
发现通用流感疫苗的保守抗原需要解决一些与当前已获许可的流感疫苗相关的问题，例如每年重新配方以及与流行亚型不匹配。后者导致疫苗效力低下，进而在易感人群和免疫功能低下的个体中引发严重的疾病并发症和高住院率。通用流感疫苗由于存在于大多数（如果不是全部）流感类型和亚型中发现的保守表位，可确保对所有流感亚型的交叉保护，例如流感基质蛋白2胞外域（M2e）和核蛋白（NP）。尽管流感M2e的免疫原性相对较低，但已证明它能在人类受试者中诱导体液反应。另一方面，流感NP可促进显著的抗流感T细胞反应。此外，NP亚基能够组装成颗粒，可进一步用作M2e肽的佐剂载体。实际上，当NP在诸如等异源宿主中融合并表达为嵌合蛋白时，其T细胞免疫优势可以转移到M2e，而不会损害抗原性。鉴于NP-M2e融合蛋白具有诱导交叉保护性抗流感细胞介导免疫和体液免疫的能力，因此其作为通用流感疫苗的潜力值得进一步探索。
