Passive Immunity to Vibrio cholerae O1 Afforded by a Human Monoclonal IgA1 Antibody Expressed in Milk.
Passive Immunity to Vibrio cholerae O1 Afforded by a Human Monoclonal IgA1 Antibody Expressed in Milk.
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DOI：
10.20411/pai.v5i1.370
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发表时间：
2020
影响因子：
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通讯作者：
Mantis NJ
中科院分区：
文献类型：
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作者：
Baranova DE;Chen L;Destrempes M;Meade H;Mantis NJ
在霍乱流行中，疾病的传播很容易超过疫苗控制措施。在转基因动物的乳汁中表达包括抗体在内的重组蛋白的技术的出现，提高了开发一种自我给药且具有成本效益的基于单克隆抗体（MAb）的预防药物以降低霍乱弧菌感染发生率的前景。我们建立了一种转基因小鼠系，其中霍乱弧菌O1脂多糖核心/脂质a中保守表位特异性的重链和轻链可变区（Fv）以全长人二聚体IgA1 （ZAC-3）表达，并分泌到哺乳期母鼠的乳汁中。在新生小鼠模型中，研究人员评估了含有ZAC-3 IgA1的乳汁对实验性霍乱感染的被动保护能力和对细菌游动行为的影响。新生小鼠被动给予含有ZAC-3 IgA1的乳汁，或在表达ZAC-3 IgA1的母鼠上哺乳，对实验性霍乱感染具有免疫力，这是通过口服攻击后12小时肠道溶解物中霍乱弧菌O1菌落形成单位的减少来测量的。体外分析表明，含有ZAC-3 higa1的牛奶在软琼脂和液体培养基中抑制了霍乱弧菌的运动，并有效地促进了细菌的凝集，这可能是细菌在体内定植减少的原因。这些结果表明，食用牛奶衍生抗体可能是一种被动预防霍乱和其他肠道病原体的策略。
In cholera epidemics, the spread of disease can easily outpace vaccine control measures. The advent of technologies enabling the expression of recombinant proteins, including antibodies, in the milk of transgenic animals raises the prospect of developing a self-administered and cost-effective monoclonal antibody (MAb)-based prophylactic to reduce the incidence of Vibrio cholerae infection. We generated a transgenic mouse line in which the heavy and light chain variable regions (Fv) specific for a conserved epitope in the core/lipid A of V. cholerae O1 lipopolysaccharide were expressed as a full-length human dimeric IgA1 (ZAC-3) and secreted into the milk of lactating dams. Milk containing ZAC-3 IgA1 was assessed for the ability to passively protect against experimental cholera infection in a newborn mouse model and to impact bacterial swimming behavior. Newborn mice that were passively administered ZAC-3 IgA1 containing milk, or that suckled on dams expressing ZAC-3 IgA1, were immune to experimental cholera infection, as measured by a reduction of V. cholerae O1 colony forming units recovered from intestinal lysates 12 hours after oral challenge. In vitro analysis revealed that ZAC-3 hIgA1-containing milk arrested V. cholerae motility in soft agar and liquid media and was effective at promoting bacterial agglutination, possibly accounting for the observed reduction in bacterial colonization in vivo. These results demonstrate that consumption of milk-derived antibodies may serve as a strategy to passively protect against cholera and possibly other enteric pathogens.