Hörner Cindy, Fiedler Anna H, Bodmer Bianca S, Walz Lisa, Scheuplein Vivian A, Hutzler Stefan, Matrosovich Mikhail N, von Messling Veronika, Mühlebach Michael D
Section 4/3: Product Testing of IVMPs, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany.
German Center for Infection Research, Gießen-Marburg-Langen, Germany.
NPJ Vaccines. 2023 Mar 24;8(1):46. doi: 10.1038/s41541-023-00643-9.
A novel Influenza A virus (subtype H7N9) emerged in spring 2013 and caused considerable mortality in zoonotically infected patients. To be prepared for potential pandemics, broadly effective and safe vaccines are crucial. Recombinant measles virus (MeV) encoding antigens of foreign pathogens constitutes a promising vector platform to generate novel vaccines. To characterize the efficacy of H7N9 antigens in a prototypic vaccine platform technology, we generated MeVs encoding either neuraminidase (N9) or hemagglutinin (H7). Moraten vaccine strain-derived vaccine candidates were rescued; they replicated with efficiency comparable to that of the measles vaccine, robustly expressed H7 and N9, and were genetically stable over 10 passages. Immunization of MeV-susceptible mice triggered the production of antibodies against H7 and N9, including hemagglutination-inhibiting and neutralizing antibodies induced by MV-H7(P) and neuraminidase-inhibiting antibodies by MV-N9(P). Vaccinated mice also developed long-lasting H7- and N9-specific T cells. Both MV-H7(P) and MV-N9(P)-vaccinated mice were protected from lethal H7N9 challenge.
一种新型甲型流感病毒(H7N9亚型)于2013年春季出现,并在人畜共患感染患者中导致了相当高的死亡率。为应对潜在的大流行,广泛有效的安全疫苗至关重要。编码外来病原体抗原的重组麻疹病毒(MeV)构成了一个有前景的载体平台,可用于研发新型疫苗。为了在一个原型疫苗平台技术中表征H7N9抗原的效力,我们构建了编码神经氨酸酶(N9)或血凝素(H7)的MeV。拯救了源自莫拉坦疫苗株的候选疫苗;它们的复制效率与麻疹疫苗相当,能强劲表达H7和N9,并且在传代10次后基因稳定。对易感染MeV的小鼠进行免疫引发了针对H7和N9的抗体产生,包括由MV-H7(P)诱导的血凝抑制和中和抗体以及由MV-N9(P)诱导的神经氨酸酶抑制抗体。接种疫苗的小鼠还产生了持久的H7和N9特异性T细胞。接种MV-H7(P)和MV-N9(P)的小鼠均受到保护,免受致死性H7N9攻击。