Influenza Centre, The Gade Institute, University of Bergen, Bergen, Norway.
Influenza Other Respir Viruses. 2011 Nov;5(6):426-37. doi: 10.1111/j.1750-2659.2011.00256.x. Epub 2011 May 9.
A candidate pandemic influenza H5N1 vaccine should provide rapid and long-lasting immunity against antigenically drifted viruses. As H5N1 viruses are poorly immunogenic, this may require a combination of immune potentiating strategies. An attractive approach is combining the intrinsic immunogenicity of virosomes with another promising adjuvant to further boost the immune response. As regulatory authorities have not yet approved a surrogate correlate of protection for H5N1 vaccines, it is important to test the protective efficacy of candidate H5N1 vaccines in a viral challenge study.
This study investigated in a murine model the protective efficacy of Matrix-M adjuvanted virosomal influenza H5N1 vaccine against highly pathogenic lethal viral challenge.
Mice were vaccinated intranasally (IN) or intramuscularly (IM) with 7·5 μg and 30 μg HA of inactivated A/Vietnam/1194/2004 (H5N1) (NIBRG-14) virosomal adjuvanted vaccine formulated with or without 10 μg of Matrix-M adjuvant and challenged IN with the highly pathogenic A/Vietnam/1194/2004 (H5N1) virus.
IM vaccination provided protection irrespective of dose and the presence of Matrix-M adjuvant, whilst the IN vaccine required adjuvant to protect against the challenge. The Matrix-M adjuvanted vaccine induced a strong and cross-reactive serum antibody response indicative of seroprotection after both IM and IN administration. In addition, the IM vaccine induced the highest frequencies of influenza specific CD4+ and CD8+ T-cells. The results confirm a high potential of Matrix-M adjuvanted virosomal vaccines and support the progress of this vaccine into a phase 1 clinical trial.
候选大流行性流感 H5N1 疫苗应提供针对抗原漂移病毒的快速和持久免疫力。由于 H5N1 病毒的免疫原性较差，这可能需要结合免疫增强策略。一种有吸引力的方法是将类病毒体的固有免疫原性与另一种有前途的佐剂结合使用，以进一步增强免疫反应。由于监管机构尚未批准 H5N1 疫苗的替代保护相关性，因此在病毒挑战研究中测试候选 H5N1 疫苗的保护效力非常重要。
本研究在小鼠模型中研究了 Matrix-M 佐剂的流感 H5N1 病毒样颗粒疫苗对高致病性致死性病毒挑战的保护效力。
通过鼻内（IN）或肌肉内（IM）接种 7.5 μg 和 30 μg 血凝素（HA）的灭活 A/Vietnam/1194/2004（H5N1）（NIBRG-14）类病毒体佐剂疫苗，用或不用 10 μg 的 Matrix-M 佐剂配制，并用高致病性 A/Vietnam/1194/2004（H5N1）病毒进行 IN 挑战。
IM 接种提供了保护，无论剂量和是否存在 Matrix-M 佐剂如何，而 IN 疫苗需要佐剂才能免受挑战。Matrix-M 佐剂疫苗诱导了强烈的交叉反应性血清抗体反应，表明在 IM 和 IN 给药后均具有血清保护作用。此外，IM 疫苗诱导了最高频率的流感特异性 CD4+和 CD8+T 细胞。这些结果证实了 Matrix-M 佐剂的类病毒体疫苗具有很高的潜力，并支持该疫苗进入 1 期临床试验。
