Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.
Athens Veterinary Diagnostic Laboratory, University of Georgia, Athens, GA 30602, USA.
Viruses. 2023 Jan 9;15(1):184. doi: 10.3390/v15010184.
The influenza neuraminidase (NA) is a promising target for next-generation vaccines. Protection induced by vaccination with the computationally optimized broadly reactive NA antigen (N1-I COBRA NA) was characterized in both influenza serologically naive and pre-immune ferret models following H1N1 (A/California/07/2009, CA/09) or H5N1 (A/Vietnam/1203/2004, Viet/04) influenza challenges. The N1-I COBRA NA vaccine elicited antibodies with neutralizing ELLA activity against both seasonal and pandemic H1N1 influenza, as well as the H5N1 influenza virus. In both models, N1-I COBRA NA-vaccinated ferrets that were challenged with CA/09 virus had similar morbidity (weight loss and clinical symptoms) as ferrets vaccinated with the CA/09 HA control vaccine. There were significantly reduced viral titers compared to the mock-vaccinated control animals. Ferrets vaccinated with N1-I COBRA NA or Viet/04 NA vaccines were protected against the H5N1 virus infection with minimal clinical symptoms and negligible weight loss. In contrast, ferrets vaccinated with the CA/09 NA vaccine lost ~10% of their original body weight with 25% mortality. Vaccination with either HA or NA vaccines did not inhibit contact transmission of CA/09 virus to naïve cage mates. Overall, the N1-I COBRA vaccine elicited protective immune responses against both H1N1 and H5N1 infections and partially mitigated disease in contact-transmission receiving ferrets. These results indicate that the N1-I COBRA NA performed similarly to the CA/09 HA and NA positive controls. Therefore, the N1-I COBRA NA alone induces protection against viruses from both H5N1 and H1N1 subtypes, indicating its value as a vaccine component in broadly protective influenza vaccines.
流感神经氨酸酶（NA）是下一代疫苗的有前途的靶标。在对 H1N1（A/加利福尼亚/07/2009，CA/09）或 H5N1（A/越南/1203/2004，Viet/04）流感进行挑战后，在血清学上未致敏和预先免疫的雪貂模型中，对经过计算优化的广泛反应性 NA 抗原（N1-I COBRA NA）进行了疫苗接种所诱导的保护作用进行了描述。N1-I COBRA NA 疫苗引发的抗体具有中和 ELLA 活性，可针对季节性和大流行性 H1N1 流感以及 H5N1 流感病毒。在这两种模型中，用 CA/09 病毒进行挑战的 N1-I COBRA NA 疫苗接种的雪貂的发病率（体重减轻和临床症状）与用 CA/09 HA 对照疫苗接种的雪貂相似。与模拟接种的对照动物相比，病毒滴度明显降低。用 N1-I COBRA NA 或 Viet/04 NA 疫苗接种的雪貂可免受 H5N1 病毒感染，症状轻微，体重减轻可忽略不计。相比之下，用 CA/09 NA 疫苗接种的雪貂体重减轻了约 10％，死亡率为 25％。用 HA 或 NA 疫苗接种均不会抑制 CA/09 病毒向未感染的笼内同伴的接触传播。总体而言，N1-I COBRA 疫苗可针对 H1N1 和 H5N1 感染产生保护性免疫应答，并在接触传播接受疫苗接种的雪貂中部分减轻疾病。这些结果表明，N1-I COBRA NA 的作用与 CA/09 HA 和 NA 阳性对照相似。因此，N1-I COBRA NA 单独诱导对 H5N1 和 H1N1 亚型病毒的保护，表明其作为广泛保护性流感疫苗的疫苗成分的价值。
