Haemophilus influenzae Protein D antibody suppression in a multi-component vaccine formulation.
Haemophilus influenzae Protein D antibody suppression in a multi-component vaccine formulation.
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DOI：
10.1002/2211-5463.13498
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发表时间：
2022-12
期刊：
影响因子：
2.6
通讯作者：
Pichichero, Michael
中科院分区：
文献类型：
--
作者：
Michel, Lea V.;Kaur, Ravinder;Gleghorn, Michael L.;Holmquist, Melody;Pryharski, Karin;Perdue, Janai;Jones, Seth P.;Jackson, Niaya;Pilo, Isabelle;Kasper, Anna;Labbe, Natalie;Pichichero, Michael
关键词：
不可分型流感嗜血杆菌（NTHi）已成为引起儿童急性中耳炎（AOM）、儿童和成人急性鼻窦炎以及成人慢性支气管炎急性加重的主要粘膜病原体。因此，迫切需要开发一种疫苗来保护免受NTHi感染。需要多组分疫苗以避免出现表达允许疫苗逃逸的修饰蛋白的菌株。蛋白D（PD）、外膜蛋白（OMP）26和蛋白6（P6）是针对NTHi的主要蛋白疫苗候选物。在使用小鼠模型的临床前研究中，我们发现重组表达的PD、OMP26和P6在作为单独疫苗接种后诱导稳健的抗体应答，但当PD和OMP26组合成单一疫苗制剂时，PD抗体水平显著降低。我们假设PD和OMP26在物理化学上相互作用以掩蔽PD抗原表位，从而导致对抗体应答的观察到的影响。然而，柱层析和质谱分析并不支持我们的假设。我们推测这种作用可能是通过蛋白疫苗免疫抗原竞争机制在体内发挥的。我们发现，当PD和OMP 26被注射到小鼠的同一条腿或不同的腿中时，使得抗原分别在相同或不同的区域淋巴结处进行免疫处理，相同腿疫苗接种的PD的抗体水平显著较低。不同的腿疫苗接种产生的PD抗体水平在数量上与单独接种PD相似。我们得出结论，将PD和OMP26混合到单一疫苗制剂中需要进一步的制剂研究。当用NTHi蛋白疫苗候选物蛋白D或OMP 26注射小鼠时，存在对每种蛋白质的强烈抗体应答。然而，当蛋白D和OMP26混合到单一疫苗制剂中时，小鼠不能产生针对蛋白D的抗体。我们提出抗体抑制的结果从两种蛋白质之间的物理化学相互作用或抗原竞争。
Nontypeable Haemophilus influenzae (NTHi) has emerged as a dominant mucosal pathogen causing acute otitis media (AOM) in children, acute sinusitis in children and adults, and acute exacerbations of chronic bronchitis in adults. Consequently, there is an urgent need to develop a vaccine to protect against NTHi infection. A multi‐component vaccine will be desirable to avoid emergence of strains expressing modified proteins allowing vaccine escape. Protein D (PD), outer membrane protein (OMP) 26, and Protein 6 (P6) are leading protein vaccine candidates against NTHi. In pre‐clinical research using mouse models, we found that recombinantly expressed PD, OMP26, and P6 induce robust antibody responses after vaccination as individual vaccines, but when PD and OMP26 were combined into a single vaccine formulation, PD antibody levels were significantly lower. We postulated that PD and OMP26 physiochemically interacted to mask PD antigenic epitopes resulting in the observed effect on antibody response. However, column chromatography and mass spectrometry analysis did not support our hypothesis. We postulated that the effect might be in vivo through the mechanism of protein vaccine immunologic antigenic competition. We found when PD and OMP26 were injected into the same leg or separate legs of mice, so that antigens were immunologically processed at the same or different regional lymph nodes, respectively, antibody levels to PD were significantly lower with same leg vaccination. Different leg vaccination produced PD antibody levels quantitatively similar to vaccination with PD alone. We conclude that mixing PD and OMP26 into a single vaccine formulation requires further formulation studies. When mice are injected with NTHi protein vaccine candidates Protein D or OMP26, there is a robust antibody response to each protein. However, when Protein D and OMP26 are mixed into a single vaccine formulation, mice fail to produce antibody to Protein D. We propose antibody suppression results from a physiochemical interaction or antigenic competition between the two proteins.
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影响因子：
3.1
作者：
Kaur, Ravinder;Pichichero, Michael
通讯作者：
Pichichero, Michael
影响因子：
3
作者：
Michel, Lea Vacca;Kaur, Ravinder;Pichichero, Michael E.
通讯作者：
Pichichero, Michael E.
影响因子：
5.5
作者：
HUNT, JD;JACKSON, DC;STEWART, DJ
通讯作者：
STEWART, DJ
影响因子：
5.5
作者：
Pichichero, Michael E.;Kaur, Ravinder;Casey, Janet R.;Sabirov, Albert;Khan, M. Nadeem;Almudevar, Anthony
通讯作者：
Almudevar, Anthony
影响因子：
15.3
作者：
BRODY, NI;SISKIND, GW
通讯作者：
SISKIND, GW