BlueWillow Biologics, Ann Arbor, MI, United States.
Fraunhofer USA Center for Molecular Biotechnology (FhCMB), Newark, DE, United States.
Vaccine. 2019 Sep 30;37(42):6162-6170. doi: 10.1016/j.vaccine.2019.08.071. Epub 2019 Sep 5.
Flu vaccines administered intramuscularly (IM) have shown seasonally fluctuating efficacy, 20-60%, throughout the last 15 years. We formulated a recombinant H5 (rH5) in our Nanovax® (NE01) (rH5/NE01) adjuvant for intranasal vaccination in ferrets. We evaluated the regimen, one vs two immunization, and cross clade protection a ferret challenge model.
Plant derived recombinant H5 (rH5) antigen was formulated with NE01 and administered intranasally to ferrets. Immunogenicity (IgG), hemagglutination inhibition (HI), and protection against lethal challenge, were measured following one or two immunizations. Protection against homologous (strain A/Indo) and heterologous (strain A/Vn) was evaluated in ferrets following two immunizations.
IN immunization with rH5/NE01 induced significant IgG levels after one and two immunizations. One vaccination did not induce any HI while low HI was measured after two immunizations. Homologous challenge with H5N1 A/ Indonesia showed 100% survival, with minimal weight loss in animals vaccinated twice compared to the unvaccinated controls. Analysis of nasal wash from these challenged ferrets vaccinated twice showed decreased viral shedding compared to unvaccinated controls. Interestingly, animals that received one vaccination showed 88% survival with moderate weight loss. Cross clade protection was evaluated using an increased antigen dose (45 µg rH5). Vaccinated animals demonstrated increased IgG and HAI antibody responses. Both homologous (A/Indo) and heterologous challenge (A/Vietnam) following two immunizations showed 100% survival with no loss of body weight. However viral clearance was more rapid against the homologous (day 3) compared to the heterologous (day 5) post challenge.
Intranasal administration of NE01 adjuvant-formulated rH5 vaccine elicited systemic and probably mucosal immunity that conferred protection against lethal challenge with homologous or heterologous viral strains. It also enhanced viral clearance with decreased shedding. These outcomes strongly suggest that intranasal immunization using NE01 against flu infections warrants clinical testing.
在过去的 15 年中，肌肉内（IM）接种的流感疫苗显示出季节性波动的效力，为 20-60%。我们在我们的 Nanovax®（NE01）（rH5/NE01）佐剂中配制了一种重组 H5（rH5），用于经鼻接种给雪貂。我们评估了方案，即一次免疫与两次免疫，以及在雪貂挑战模型中的跨谱系保护。
植物来源的重组 H5（rH5）抗原与 NE01 一起配制，并经鼻内接种给雪貂。在一次或两次免疫后，测量免疫原性（IgG）、血凝抑制（HI）和对致死性挑战的保护。在两次免疫后，在雪貂中评估了对同源（株 A/Indo）和异源（株 A/Vn）的保护。
rH5/NE01 的单次免疫可诱导显著的 IgG 水平，一次和两次免疫均可诱导。一次免疫不能诱导任何 HI，而两次免疫后只能测量到低 HI。用 H5N1 A/印度尼西亚进行同源挑战显示 100%的存活率，与未接种疫苗的对照组相比，两次接种疫苗的动物体重减轻最小。对这些经挑战的雪貂进行两次接种的鼻冲洗分析显示，与未接种疫苗的对照组相比，病毒脱落减少。有趣的是，接受一次接种的动物显示 88%的存活率和中度体重减轻。使用增加的抗原剂量（45μg rH5）评估了跨谱系保护。接种疫苗的动物显示出增加的 IgG 和 HAI 抗体反应。两次免疫后，用同源（A/Indo）和异源（A/Vietnam）进行挑战均显示 100%的存活率，体重无减轻。然而，与异源（第 5 天）相比，同源（第 3 天）的病毒清除更快。
NE01 佐剂配制的 rH5 疫苗经鼻内给药可引起全身，可能还有黏膜免疫，可对抗同源或异源病毒株的致死性挑战。它还增强了病毒清除，减少了脱落。这些结果强烈表明，使用 NE01 经鼻免疫流感感染值得进行临床测试。
