Allen James D, Zhang Xiaojian, Medina Jessica M, Thomas Matthew H, Lynch Amanda, Nelson Ron, Aguirre Julia, Ross Ted M
Center for Vaccines and Immunology, University of Georgia, Athens, GA 30605, USA.
Department of Infectious Diseases, University of Georgia, Athens, GA 30605, USA.
Vaccines (Basel). 2024 Dec 2;12(12):1364. doi: 10.3390/vaccines12121364.
Standard-of-care influenza vaccines contain antigens that are typically derived from components of wild type (WT) influenza viruses. Often, these antigens elicit strain-specific immune responses and are susceptible to mismatch in seasons where antigenic drift is prevalent. Thanks to advances in viral surveillance and sequencing, influenza vaccine antigens can now be optimized using computationally derived methodologies and algorithms to enhance their immunogenicity. Mice and ferrets that had been previously exposed to historical H1N1 and H3N2 influenza viruses were vaccinated intramuscularly with bivalent mixtures of H1 and H3 recombinant hemagglutinin (rHA) proteins, which were generated using a computationally optimized broadly reactive antigen (COBRA) design methodology. The vaccine antigens were mixed with a cationic lipid nanoparticle adjuvant, Infectimune, which promotes both humoral and cellular immune responses. Mice and ferrets vaccinated with Infectimune and COBRA rHAs elicited protective antibody titers against panels of H1N1 and H3N2 influenza viruses isolated over the past 10 years. These animals also had antibodies that neutralized numerous modern H1N1 and H3N2 influenza viruses in vitro. When challenged with the A/Victoria/2570/2019 H1N1 influenza virus, the COBRA rHA vaccinated animals had minimal weight loss, and no detectable virus was present in their respiratory tissues on day 3 post-infection. These results demonstrate that COBRA rHA vaccines formulated with Infectimune elicit protective antibody responses against influenza strains, which were isolated across periods of time when standard-of-care vaccines were frequently reformulated, thus reducing the need to update vaccines on a nearly annual basis.
标准护理流感疫苗所含抗原通常源自野生型（WT）流感病毒的成分。通常，这些抗原会引发毒株特异性免疫反应，并且在抗原漂移普遍存在的季节容易出现错配情况。得益于病毒监测和测序技术的进步，现在可以使用计算得出的方法和算法来优化流感疫苗抗原，以增强其免疫原性。先前接触过历史H1N1和H3N2流感病毒的小鼠和雪貂通过肌肉注射接种了H1和H3重组血凝素（rHA）蛋白的二价混合物，这些蛋白是使用计算优化的广谱反应性抗原（COBRA）设计方法生成的。疫苗抗原与阳离子脂质纳米颗粒佐剂Infectimune混合，该佐剂可促进体液免疫和细胞免疫反应。用Infectimune和COBRA rHAs接种的小鼠和雪貂产生了针对过去10年中分离出的一系列H1N1和H3N2流感病毒的保护性抗体滴度。这些动物还具有在体外中和多种现代H1N1和H3N2流感病毒的抗体。当用A/维多利亚/2570/2019 H1N1流感病毒攻击时，接种COBRA rHA的动物体重减轻最小，并且在感染后第3天其呼吸道组织中未检测到病毒。这些结果表明，用Infectimune配制的COBRA rHA疫苗可引发针对流感毒株的保护性抗体反应，这些毒株是在标准护理疫苗经常重新配制的时间段内分离出来的，从而减少了几乎每年更新疫苗的必要性。
