BioIndustrial Division, Instituto/Fundação Butantan, SP, Brazil.
Vaccine. 2010 Mar 16;28(13):2505-9. doi: 10.1016/j.vaccine.2010.01.044. Epub 2010 Jan 30.
Consecutive lots of H5N1 (A/Vietnam/1194/2004 - NIBRG-14) split virion and whole virus vaccines were produced in a pilot-scale laboratory. The average yields of vaccine doses (15 microg HA) per egg were 0.57 doses for H5N1 split virion vaccine and 1.12 for H5N1 whole virus vaccine, compared to 2.09 doses for the seasonal H3N2 split virion vaccine. H5N1 split virion vaccine lots complied with WHO protein content criteria, while some lots of the H5N1 whole virus vaccine showed protein content per dose higher than the limit established. All lots of both vaccines showed ovalbumin (OVA) concentration below the recommended limit. Dose sparing strategies using adjuvant formulations using aluminum hydroxide (Al(OH)(3)) and monophosphoryl lipid A (MPLA) from Bordetella pertussis were tested in mice. Both 3.75 microg HA and 7.5 microg HA of H5N1 split virion vaccine with Al(OH)(3) or Al(OH)(3) plus MPLA in aqueous suspension showed higher hemagglutination-inhibition (HAI) titers when compared to the same vaccine dose without any adjuvant. Immunization with the H5N1 inactivated whole virus vaccine was also performed using 3.75 microg HA and HAI titers were higher than those induced by the split virion vaccine. Moreover, the use of Al(OH)(3) with MPLA as an emulsion induced a further increase in HAI titers.
连续批次的 H5N1（A/Vietnam/1194/2004-NIBRG-14）裂病毒和全病毒疫苗在中试规模实验室中生产。每只鸡蛋的疫苗剂量（15μgHA）的平均产量为 H5N1 裂病毒疫苗 0.57 剂和 H5N1 全病毒疫苗 1.12 剂，而季节性 H3N2 裂病毒疫苗为 2.09 剂。H5N1 裂病毒疫苗批次符合世卫组织蛋白质含量标准，而一些 H5N1 全病毒疫苗批次的剂量蛋白含量高于规定的限制。两种疫苗的所有批次的卵清白蛋白（OVA）浓度均低于推荐限量。在小鼠中测试了使用佐剂配方的剂量节约策略，佐剂配方使用来自百日咳博德特氏菌的氢氧化铝（Al（OH）（3））和单磷酰脂质 A（MPLA）。与不含任何佐剂的相同疫苗剂量相比，3.75μgHA 和 7.5μgHA 的 H5N1 裂病毒疫苗与 Al（OH）（3）或 Al（OH）（3）加 MPLA 水悬浮液中的血凝抑制（HAI）滴度更高。使用 3.75μgHA 对 H5N1 灭活全病毒疫苗进行免疫接种，HAI 滴度高于裂病毒疫苗诱导的滴度。此外，使用 Al（OH）（3）与 MPLA 作为乳剂可进一步提高 HAI 滴度。
