Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.
PLoS One. 2012;7(1):e30252. doi: 10.1371/journal.pone.0030252. Epub 2012 Jan 18.
The increase in recent outbreaks and unpredictable changes of highly pathogenic avian influenza (HPAI) H5N1 in birds and humans highlights the urgent need to develop a cross-protective H5N1 vaccine. We here report our development of a multiple-clade H5N1 influenza vaccine tested for immunogenicity and efficacy to confer cross-protection in an animal model.
METHODOLOGY/PRINCIPAL FINDINGS: Mice received two doses of influenza split vaccine with oil-in-water emulsion adjuvant SP01 by intranasal administration separated by two weeks. Single vaccines (3 µg HA per dose) included rg-A/Vietnam/1203/2004(Clade 1), rg-A/Indonesia/05/2005(Clade 2.1), and rg-A/Anhui/1/2005(Clade 2.3.4). The trivalent vaccine contained 1 µg HA per dose of each single vaccine. Importantly, complete cross-protection was observed in mice immunized using trivalent vaccine with oil-in-water emulsion adjuvant SP01 that was subsequently challenged with the lethal A/OT/SZ/097/03 influenza strain (Clade 0), whereas only the survival rate was up to 60% in single A/Anhui/1/2005 vaccine group.
CONCLUSION/SIGNIFICANCE: Our findings demonstrated that the multiple-clade H5N1 influenza vaccine was able to elicit a cross-protective immune response to heterologous HPAI H5N1 virus, thus giving rise to a broadly cross-reactive vaccine to potential prevention use ahead of the strain-specific pandemic influenza vaccine in the event of an HPAI H5N1 influenza outbreak. Also, the multiple-clade adjuvanted vaccine could be useful in allowing timely initiation of vaccination against unknown pandemic virus.
近期高致病性禽流感（HPAI）H5N1 在鸟类和人类中的爆发增加，且其变化不可预测，这凸显了开发针对 H5N1 的交叉保护疫苗的迫切需要。在此，我们报告了一种多谱系 H5N1 流感疫苗的开发情况，该疫苗已在动物模型中进行了免疫原性和疗效测试，以提供交叉保护。
方法/主要发现：通过鼻腔内给药，用含油包水乳剂佐剂 SP01 的流感裂解疫苗对小鼠进行两次免疫，两次免疫间隔两周。单价疫苗（每剂 3 µg HA）包括 rg-A/Vietnam/1203/2004（Clade 1）、rg-A/Indonesia/05/2005（Clade 2.1）和 rg-A/Anhui/1/2005（Clade 2.3.4）。三价疫苗每剂含各单价疫苗 1 µg HA。重要的是，用含油包水乳剂佐剂 SP01 的三价疫苗免疫的小鼠随后用致死性 A/OT/SZ/097/03 流感株（Clade 0）进行攻毒，观察到完全的交叉保护，而仅用单价 A/Anhui/1/2005 疫苗组的存活率高达 60%。
结论/意义：我们的研究结果表明，多谱系 H5N1 流感疫苗能够引发针对异源高致病性禽流感 H5N1 病毒的交叉保护免疫反应，从而产生一种广泛交叉反应的疫苗，以备在 HPAI H5N1 流感爆发时，在针对特定流行株的流感疫苗之前，提前用于潜在的预防。此外，多谱系佐剂疫苗可能有助于及时启动针对未知大流行病毒的疫苗接种。
