Vaccine-specific antibody secreting cells are a robust early marker of LAIV-induced B-cell response in ferrets
Vaccine-specific antibody secreting cells are a robust early marker of LAIV-induced B-cell response in ferrets
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DOI：
10.1016/j.vaccine.2011.11.001
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发表时间：
2012-01-05
期刊：
影响因子：
5.5
通讯作者：
Woo, Jennifer
中科院分区：
文献类型：
--
作者：
Cherukuri, Anu;Servat, Esteban;Woo, Jennifer
目前，还没有完全阐明减毒活流感疫苗（LAIV）在人体中的有效性的一组强有力的免疫相关性。血清血凝抑制（HAI）试验历来用于测量对注射灭活流感疫苗的体液免疫应答。然而，血清抗体滴度不能可靠地反映LAIV的完整作用机制，LAIV是一种鼻内递送的疫苗，预期除体液免疫应答外还诱导局部粘膜和细胞免疫应答。因此，我们设计了一项研究，以评估在流感感染的雪貂动物模型中LAIV疫苗接种的潜在免疫相关性。雪貂接种LAIV的剂量增加，四周后用同源野生型（wt）H1N1毒株攻击。LAIV疫苗接种后测量的体液免疫应答包括HAI、血清抗体和抗体分泌细胞（ASC）;发现这些应答与该模型中给予的LAIV剂量水平相关。通过测量鼻洗液和肺组织中wt病毒复制的抑制来确定对wt病毒攻击的保护。结果表明，LAIV剂量>5.0 log（10）空斑形成单位（PFU）引起疫苗特异性IgG和伊加ASC频率，并在肺中诱导完全保护。此外，我们开发了一种新的模型，其利用血清阳性的老年雪貂来证明在先前野生型流感感染的背景下，LAIV即使在不存在血清抗体应答的情况下也诱导稳健的疫苗特异性B细胞应答，该结果表明由LAIV产生的效应子B细胞应答不受先前病毒暴露的抑制。最后，我们证明了LAIV elevin株特异性记忆B细胞反应是可测量的野生型流感感染的背景。总之，这些研究的结果将抗原特异性ASC频率确定为LAIV诱导的B细胞免疫应答的有用早期生物标志物。(C)2011爱思唯尔有限公司保留所有权利。
Currently, a robust set of immune correlates for live attenuated influenza vaccine (LAIV) efficacy in humans has not been fully elucidated. The serum hemagglutination inhibition (HAI) assay has been historically used to measure humoral immune responses to injectable inactivated influenza vaccination. However, serum antibody titers do not reliably reflect the complete mechanism of action of LAIV, which is an intranasally delivered vaccine and is expected to induce local mucosal and cellular immune responses in addition to humoral immune responses. Therefore, we designed a study to evaluate potential immune correlates of LAIV vaccination in the ferret animal model of influenza infection. Ferrets were vaccinated with increasing doses of LAIV and four weeks later challenged with a homologous wild-type (wt) H1N1 strain. Humoral immune responses measured following LAIV vaccination included HAI, serum antibodies and antibody secreting cells (ASC); and the responses were found to correlate with the dose level of LAIV administered in this model. Protection from wt virus challenge was determined by measuring inhibition of wt viral replication in nasal washes and in lung tissue. Results demonstrated that LAIV doses >5.0 log(10) Plaque Forming Units (PFU) elicited vaccine-specific IgG and IgA ASC frequencies and induced complete protection in the lungs. Further, we developed a novel model utilizing seropositive older ferrets to demonstrate that in the background of previous wt influenza infection LAIV induces a robust vaccine-specific B-cell response even in the absence of serum antibody response, a result that suggests that effector B-cell responses generated by LAIV are not inhibited by prior viral exposure. Finally, we demonstrated that LAIV elicits strain-specific memory B-cell responses that are measurable in a background of wt influenza infections. Taken together, results from these studies identified the antigen-specific ASC frequency as a useful early biomarker of LAIV-induced B-cell immune response. (C) 2011 Elsevier Ltd. All rights reserved.