FluGen, Inc., Madison, WI 53711, USA.
IIT Research Institute, Chicago, IL 60616, USA.
Vaccine. 2018 Aug 9;36(33):5097-5103. doi: 10.1016/j.vaccine.2018.06.053. Epub 2018 Jul 13.
Current influenza vaccines do not provide effective protection against heterologous influenza viruses. The ability of the novel M2SR influenza vaccine to protect against drifted influenza viruses was evaluated in naïve ferrets and in ferrets with pre-existing immunity to influenza. In naïve ferrets, M2SR provided similar protection against drifted challenge viruses as the comparator vaccine, FluMist®. However, in ferrets with pre-existing immunity, M2SR provided superior protection than FluMist in two model systems. In the first model, ferrets were infected with influenza A H1N1pdm and influenza B viruses to mimic the diverse influenza exposure in humans. The pre-infected ferrets, seropositive to H1N1pdm and influenza B but seronegative to H3N2, were then vaccinated with H3N2 M2SR or monovalent H3N2 FluMist virus (A/Brisbane/10/2007, clade 1) and challenged 6 weeks later with a drifted H3N2 virus (clade 3C.2a). Antibody titers to Brisbane/10/2007 were higher in M2SR vaccinated ferrets than in FluMist vaccinated ferrets in the pre-infected ferrets whereas the opposite was observed in naïve ferrets. After challenge with drifted H3N2 virus, M2SR provided superior protection than FluMist monovalent vaccine. In the second model, the impact of homologous pre-existing immunity upon vaccine-induced protection was evaluated. Ferrets, pre-infected with H1N1pdm virus, were vaccinated 90 days later with H1N1pdm M2SR or FluMist monovalent vaccine and challenged 6 weeks later with a pre-pandemic seasonal H1N1 virus, A/Brisbane/59/2007 (Bris59). While cross-reactive serum IgG antibodies against the Bris59 HA were detected after vaccination, anti-Bris59 hemagglutination inhibition antibodies were only detected post-challenge. M2SR provided better protection against Bris59 challenge than FluMist suggesting that homologous pre-existing immunity affected FluMist virus to a greater degree than M2SR. These results suggest that the single replication intranasal M2SR vaccine provides effective protection against drifted influenza A viruses not only in naïve ferrets but also in those with pre-existing immunity in contrast to FluMist viruses.
目前的流感疫苗不能为异源流感病毒提供有效保护。本研究评估了新型 M2SR 流感疫苗对漂移流感病毒的保护作用，实验对象为无免疫史的雪貂和已有流感免疫史的雪貂。在无免疫史的雪貂中，M2SR 对漂移挑战病毒的保护作用与对照疫苗 FluMist®相似。然而，在已有免疫史的雪貂中，M2SR 在两种模型系统中的保护作用优于 FluMist。在第一个模型中，雪貂感染甲型 H1N1pdm 和乙型流感病毒，以模拟人类接触的多样化流感病毒。感染后的雪貂对 H1N1pdm 和乙型流感病毒呈血清阳性反应，但对 H3N2 呈血清阴性反应，然后用 H3N2 M2SR 或单价 H3N2 FluMist 病毒（A/Brisbane/10/2007，分支 1）进行疫苗接种，并在 6 周后用漂移的 H3N2 病毒（分支 3C.2a）进行攻毒。在感染后的雪貂中，M2SR 接种组的 Brisbane/10/2007 抗体滴度高于 FluMist 接种组，而在无免疫史的雪貂中则相反。用漂移的 H3N2 病毒攻毒后，M2SR 提供的保护优于 FluMist 单价疫苗。在第二个模型中，评估了同源性预先存在的免疫对疫苗诱导的保护作用的影响。感染 H1N1pdm 病毒的雪貂在 90 天后用 H1N1pdm M2SR 或 FluMist 单价疫苗进行接种，并在 6 周后用流行前季节性 H1N1 病毒 A/Brisbane/59/2007（Bris59）进行攻毒。接种后检测到针对 Bris59 HA 的交叉反应性血清 IgG 抗体，但仅在攻毒后检测到抗 Bris59 血凝抑制抗体。M2SR 对 Bris59 攻毒的保护作用优于 FluMist，表明同源预先存在的免疫对 FluMist 病毒的影响大于 M2SR。这些结果表明，与 FluMist 病毒相比，单次复制的鼻内 M2SR 疫苗不仅对无免疫史的雪貂，而且对已有免疫史的雪貂均能有效预防漂移的甲型流感病毒。
