Protection against nontypeable Haemophilus influenzae challenges by mucosal vaccination with a detoxified lipooligosaccharide conjugate in two chinchilla models
Protection against nontypeable Haemophilus influenzae challenges by mucosal vaccination with a detoxified lipooligosaccharide conjugate in two chinchilla models
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DOI：
10.1016/j.micinf.2009.09.006
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发表时间：
2010-01-01
影响因子：
5.8
通讯作者：
Gu, Xin-Xing
中科院分区：
文献类型：
--
作者：
Hong, Wenzhou;Peng, Daxin;Gu, Xin-Xing
中耳炎（OM）可在上呼吸道感染开始后发生。通过粘膜接种抑制细菌在鼻咽部（NP）的定植可能通过减少细菌侵入中耳（MEs）来预防OM。在这项研究中，80只龙猫用非分型流感嗜血杆菌（NTHi）与霍乱毒素（CT）混合的脱毒低脂寡糖(dLOS)-破伤风类毒素结合疫苗经鼻免疫。所有接种过疫苗的动物的粘膜和血清抗los抗体水平均有所升高。最后一次免疫2周后，40只龙猫接种NTHi以评估NP定植和ME感染，其余动物接种经口结核菌（T.B.）以检查OM的发展。与对照组相比，接种疫苗不仅抑制了感染组细菌在NP中的定植和向MEs的传播，而且抑制了感染组细菌在NP中的定植和向未感染组的传播。虽然在结核病攻击后，两组的攻击耳朵都没有发现差异，但在接种疫苗的动物中，从NP和未攻击的耳朵中早期清除了NTHi，并且未攻击的汽车中OM的严重程度较低。目前的结果以及我们之前的数据表明，粘膜接种能够抑制NTHi NP定植并预防龙猫OM的发生；免疫攻毒模型适用于粘膜疫苗试验，结核杆菌攻毒模型适用于全身疫苗试验。Elsevier Masson SAS出版。
Otitis media (OM) can occur following outset of upper respiratory tract infections. Inhibition of bacterial colonization in nasopharynx (NP) by mucosal vaccination may prevent OM by reducing bacterial invasion of the middle ears (MEs). In this study, 80 chinchillas were intranasally (i.n.) immunized with a detoxified lipooligosaccharide (dLOS)-tetanus toxoid conjugate vaccine of nontypeable Haemophilus influenzae (NTHi) mixed with cholera toxin (CT) or CT alone. All vaccinated animals responded with elevated levels of mucosal and serum anti-LOS antibodies. Two weeks after the last immunization, 40 chinchillas were challenged i.n. with NTHi to evaluate NP colonization and ME infection while the rest of the animals were challenged transbullarly (T.B.) to examine the development of OM. Compared to the control group, the vaccination inhibited not only bacterial colonization in NP and transmission to MEs in the i.n. challenge group but also bacterial colonization in NP and transmission to unchallenged ears in the T.B. challenge group. Though no difference was found in the challenged ears of either group right after the T.B. challenge, an early clearance of NTHi from NP and unchallenged ears as well as less severity of OM in the unchallenged cars were observed in vaccinated animals. Current results along with our previous data indicate that mucosal vaccination is capable of inhibiting NTHi NP colonization and preventing OM occurrence in chinchillas; the i.n. challenge model is preferable for testing the mucosal vaccines while the T.B. challenge model is superior for testing the systemic vaccines. Published by Elsevier Masson SAS.