Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea.
Department of Biosystems and Bioengineering, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
J Microbiol Biotechnol. 2021 Feb 28;31(2):304-316. doi: 10.4014/jmb.2011.11029.
Vaccination is the most effective way to prevent influenza virus infections. However, conventional vaccines based on hemagglutinin (HA) have to be annually updated because the HA of influenza viruses constantly mutates. In this study, we produced a 3M2e-3HA2-NP chimeric protein as a vaccine antigen candidate using an expression system. The vaccination of chimeric protein (15 μg) conferred complete protection against A/Puerto Rico/8/1934 (H1N1; PR8) in mice. It strongly induced influenza virus-specific antibody responses, cytotoxic T lymphocyte activity, and antibody-dependent cellular cytotoxicity. To spare the dose and enhance the cross-reactivity of the chimeric, we used a complex of poly-γ-glutamic acid and alum (PGA/alum) as an adjuvant. PGA/alum-adjuvanted, low-dose chimeric protein (1 or 5 μg) exhibited higher cross-protective effects against influenza A viruses (PR8, CA04, and H3N2) compared with those of chimeric alone or alum-adjuvanted proteins in vaccinated mice. Moreover, the depletion of CD4 T, CD8 T, and NK cells reduced the survival rate and efficacy of the PGA/alum-adjuvanted chimeric protein. Collectively, the vaccination of PGA/alum-adjuvanted chimeric protein induced strong protection efficacy against homologous and heterologous influenza viruses in mice, which suggests that it may be a promising universal influenza vaccine candidate.
疫苗接种是预防流感病毒感染的最有效方法。然而，基于血凝素 (HA) 的传统疫苗每年都需要更新，因为流感病毒的 HA 不断发生突变。在这项研究中，我们使用表达系统生产了一种 3M2e-3HA2-NP 嵌合蛋白作为疫苗抗原候选物。该嵌合蛋白（15 μg）的疫苗接种可使小鼠完全免受 A/Puerto Rico/8/1934（H1N1；PR8）的侵害。它强烈诱导流感病毒特异性抗体反应、细胞毒性 T 淋巴细胞活性和抗体依赖性细胞毒性。为了节省剂量并增强嵌合蛋白的交叉反应性，我们使用聚谷氨酸和明矾（PGA/明矾）复合物作为佐剂。与单独使用嵌合蛋白或明矾佐剂的蛋白相比，PGA/明矾佐剂的低剂量嵌合蛋白（1 或 5 μg）在接种小鼠中表现出更高的针对流感 A 病毒（PR8、CA04 和 H3N2）的交叉保护作用。此外，CD4 T、CD8 T 和 NK 细胞的耗竭降低了 PGA/明矾佐剂嵌合蛋白的存活率和功效。总之，PGA/明矾佐剂嵌合蛋白的接种可诱导小鼠对同源和异源流感病毒产生强烈的保护效力，这表明它可能是一种有前途的通用流感疫苗候选物。
