Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant
Intranasal Immunization of Ferrets with Commercial Trivalent Influenza Vaccines Formulated in a Nanoemulsion-Based Adjuvant
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DOI：
10.1128/cvi.00035-11
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发表时间：
2011-07-01
影响因子：
--
通讯作者：
Baker, James R., Jr.
中科院分区：
文献类型：
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作者：
Hamouda, Tarek;Sutcliffe, Joyce A.;Baker, James R., Jr.
NB-1008是一种表面活性剂稳定的水包大豆油纳米乳剂（NE）佐剂，通过简单混合将流感病毒抗原掺入NE中。鼻内给予抗原与NE佐剂有效地产生粘膜和血清抗体应答以及强有力的细胞Th 1免疫应答。为了证明W（80）5EC NE的佐剂作用，将用于肌内施用的灭活的商业流感疫苗（Fluzone或Fluvirin）与W（80）5EC NE佐剂混合，并鼻内施用给未接种的雪貂。单次鼻内免疫后，含佐剂的流感疫苗引起血清血凝抑制（HAI）几何平均滴度（GMT）升高，疫苗中存在的三种血凝素（HA）抗原的滴度范围为196至905，滴度约高出19至90倍标准肌内商业无佐剂流感疫苗剂量的1/50。针对存在的三种病毒株中的每一种，实现了67%至100%的血清转化率。含佐剂的鼻用流感疫苗还对疫苗中不存在的其他五种H3 N2流感病毒株产生了显著的交叉免疫，并在用同源活病毒攻击后产生了无菌免疫。在249只接受含佐剂流感疫苗的雪貂中未观察到安全性问题。这些发现证明了W（80）5EC NE对鼻内给药流感疫苗的佐剂能力，并为研究鼻内W（80）5EC佐剂流感疫苗在人体中的应用提供了基础。
NB-1008 is a surfactant-stabilized soybean oil-in-water nanoemulsion (NE) adjuvant with influenza virus antigen incorporated into the NE by simple mixing. Intranasal administration of the antigen with NE adjuvant efficiently produces both mucosal and serum antibody responses as well as a robust cellular Th1 immune response. To demonstrate the adjuvant effect of the W(80)5EC NE, a killed commercial influenza vaccine for intramuscular administration (Fluzone or Fluvirin) was mixed with the W(80)5EC NE adjuvant and administered intranasally to naive ferrets. After a single intranasal immunization, the adjuvanted influenza vaccine elicited elevated serum hemagglutination inhibition (HAI) geometric mean titers (GMTs) ranging from 196 to 905 for the three hemagglutinin (HA) antigens present in the vaccine, which are approximately 19- to 90-fold higher titers at 1/50 the standard intramuscular commercial nonadjuvanted influenza vaccine dose. Seroconversion rates of 67% to 100% were achieved against each of the three viral strains present. The adjuvanted nasal influenza vaccine also produced significant cross immunity to five other H3N2 influenza virus strains not present in the vaccine and produced sterile immunity after challenge with homologous live virus. No safety issues were observed in 249 ferrets receiving the adjuvanted influenza vaccine. These findings demonstrate the ability of W(80)5EC NE to adjuvant nasally administered influenza vaccine and provide a basis for studying the intranasal W(80)5EC-adjuvanted influenza vaccine in humans.