A bivalent pneumococcal histidine triad protein D-choline-binding protein A vaccine elicits functional antibodies that passively protect mice from Streptococcus pneumoniae challenge.
A bivalent pneumococcal histidine triad protein D-choline-binding protein A vaccine elicits functional antibodies that passively protect mice from Streptococcus pneumoniae challenge.
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DOI：
10.1080/21645515.2016.1202389
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发表时间：
2016-11
影响因子：
4.8
通讯作者：
Brookes RH
中科院分区：
文献类型：
--
作者：
Ochs MM;Williams K;Sheung A;Lheritier P;Visan L;Rouleau N;Proust E;de Montfort A;Tang M;Mari K;Hopfer R;Gallichan S;Brookes RH
基于保守肺炎球菌蛋白的疫苗正在研究中，因为肺炎球菌多糖和多糖结合疫苗的血清型复盖不完整，并可能最终由于血清型替换而减少。在这里，我们检测了候选双价胆碱结合蛋白A-肺炎球菌组氨酸三联体蛋白D(PCPA-PhtD)疫苗诱导的人类抗体的功能性。在建立的被动保护模型中，对接种了PCPA-PhtD候选疫苗的受试者免疫前和免疫后的血清进行了测试，在被动保护模型中，小鼠通过静脉注射肺炎链球菌A66.1株进行攻击。采用酶联免疫吸附试验(EL ISA)检测血清抗体浓度。用基于流式细胞术的方法检测血清抗体与细菌表面的结合。在被动保护模式中，根据免疫前样本活性低的特点选择20名受试者的血清。细菌表面结合与抗PCPA的相关性(0.87；p<；0.0001)大于与抗PhtD的相关性(0.71；p<；0.0001)。在被动保护试验中，预测生存的优势比为4 70[95%可信区间(CI)，46.8 to>；999.9]，高于抗PhtD浓度(3.4[95%CI，1.9~5.6])或细菌表面结合(9.4[95%CI，3.6~2 4.3])。混合免疫后血清也保护小鼠免受肺炎链球菌3型菌株WU2的攻击。双价候选疫苗诱导的抗PCPA和抗PhtD抗体均可介导对肺炎链球菌的保护作用。该结果还表明，该抗体效价可作为评估肺炎球菌蛋白疫苗诱导的抗体功能活性的替代指标。
Vaccines based on conserved pneumococcal proteins are being investigated because serotype coverage by pneumococcal polysaccharide and polysaccharide conjugate vaccines is incomplete and may eventually decrease due to serotype replacement. Here, we examined the functionality of human antibodies induced by a candidate bivalent choline-binding protein A- pneumococcal histidine triad protein D (PcpA-PhtD) vaccine. Pre- and post-immune sera from subjects who had been vaccinated with the PcpA-PhtD candidate vaccine were tested in an established passive protection model in which mice were challenged by intravenous injection with Streptococcus pneumoniae serotype 3 strain A66.1. Serum antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Bacterial surface binding by serum antibodies was determined by a flow cytometry-based assay. Sera from 20 subjects were selected based on low activity of pre-immune samples in the passive protection model. Bacterial surface binding correlated more strongly with anti-PcpA (0.87; p < 0.0001) than with anti-PhtD (0.71; p < 0.0001). The odds ratio for predicting survival in the passive protection assay was higher for the anti-PcpA concentration (470 [95% confidence interval (CI), 46.8 to >999.9]) than for the anti-PhtD concentration (3.4 [95% CI, 1.9 to 5.6]) or bacterial surface binding (9.4 [95% CI, 3.6 to 24.3]). Pooled post-immune serum also protected mice against a challenge with S. pneumoniae serotype 3 strain WU2. Both anti-PcpA and anti-PhtD antibodies induced by the bivalent candidate vaccine mediate protection against S. pneumoniae. The results also showed that the ELISA titer might be useful as a surrogate for estimating the functional activity of antibodies induced by pneumococcal protein vaccines.
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影响因子：
3.1
作者：
Glover, David T.;Hollingshead, Susan K.;Briles, David E.
通讯作者：
Briles, David E.
影响因子：
5.5
作者：
Seiberling, Michael;Bologa, Monica;Gurunathan, Sanjay
通讯作者：
Gurunathan, Sanjay
影响因子：
3.1
作者：
Khan, M. N.;Pichichero, M. E.
通讯作者：
Pichichero, M. E.
影响因子：
5.5
作者：
Denoel, Philippe;Philipp, Mario T.;Doyle, Lara;Martin, Dale;Carletti, Georges;Poolman, Jan T.
通讯作者：
Poolman, Jan T.
影响因子：
3.1
作者：
Kaur, Ravinder;Surendran, Naveen;Pichichero, Michael E.
通讯作者：
Pichichero, Michael E.