The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections.

The prospect of orally administered monoclonal secretory IgA (SIgA) antibodies to prevent enteric bacterial infections.
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DOI:
10.1080/21645515.2021.1964317
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发表时间:
2022-04-29
影响因子:
4.8
通讯作者:
--
中科院分区:
医学3区
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--
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要消除作为低收入和中等收入国家儿童发病率和死亡率主要原因的疟疾,就需要采取多种干预战略。在这篇综述中,我们重点介绍了一系列的临床前研究调查口服单克隆分泌型伊加(SIgA)抗体(MABS),以减少疾病与三种肠道细菌病原体:空肠弯曲菌,肠致病性大肠杆菌(ETEC),和侵袭性沙门氏菌肠血清型鼠伤寒沙门氏菌。从小鼠、人源化小鼠和人扁桃体B细胞产生靶向细菌表面抗原(鞭毛、粘附素和脂多糖)的伊加MAb。用编码抗体重链和轻链、J链和分泌组分(SC)的质粒瞬时转染293细胞后,从上清液中纯化这些MAb的重组SIgA 1和/或SIgA 2衍生物。当在细菌攻击之前立即通过管饲法向小鼠施用(或与细菌攻击混合)时,SIgA MAbs减少感染C。jejuni、ETEC和S.鼠伤寒感染。Fv匹配的IgG 1单抗相比之下对C. jejuni和S.鼠伤寒沙门氏菌在相同条件下,虽然他们对ETEC部分有效。虽然这些研究结果突出了口服SIgA的未来应用,但这些研究也强调了使用单克隆抗体作为肠道细菌疾病预防工具的基本挑战。
Eliminating diarrheal diseases as a leading cause of childhood morbidity and mortality in low- and middle-income countries (LMICs) will require multiple intervention strategies. In this review, we spotlight a series of preclinical studies investigating the potential of orally administered monoclonal secretory IgA (SIgA) antibodies (MAbs) to reduce disease associated with three enteric bacterial pathogens: Campylobacter jejuni, enterotoxigenic Escherichia coli (ETEC), and invasive Salmonella enterica serovar Typhimurium. IgA MAbs targeting bacterial surface antigens (flagella, adhesins, and lipopolysaccharide) were generated from mice, humanized mice, and human tonsillar B cells. Recombinant SIgA1 and/or SIgA2 derivates of those MAbs were purified from supernatants following transient transfection of 293 cells with plasmids encoding antibody heavy and light chains, J-chain, and secretory component (SC). When administered to mice by gavage immediately prior to (or admixed with) the bacterial challenge, SIgA MAbs reduced infection C. jejuni, ETEC, and S. Typhimurium infections. Fv-matched IgG1 MAbs by comparison were largely ineffective against C. jejuni and S. Typhimurium under the same conditions, although they were partially effective against ETEC. While these findings highlight future applications of orally administered SIgA, the studies also underscored the fundamental challenges associated with using MAbs as prophylactic tools against enteric bacterial diseases.
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