Differential profiles and inhibitory effect on rotavirus vaccines of nonantibody components in breast milk from mothers in developing and developed countries.
Differential profiles and inhibitory effect on rotavirus vaccines of nonantibody components in breast milk from mothers in developing and developed countries.
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DOI：
10.1097/inf.0b013e318290646d
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发表时间：
2013-08
期刊：
影响因子：
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通讯作者：
Jiang B
中科院分区：
文献类型：
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作者：
Moon SS;Tate JE;Ray P;Dennehy PH;Archary D;Coutsoudis A;Bland R;Newell ML;Glass RI;Parashar U;Jiang B
口服轮状病毒活疫苗对发展中国家儿童的免疫原性和有效性低于中等收入和工业化国家的儿童，这些差异的基础尚未完全了解。最近，我们证明，与美国母亲的母乳相比，印度母亲的母乳对轮状病毒具有显著更高的伊加和中和活性，这可能会降低到达肠道的轮状病毒疫苗的有效滴度。我们扩展了我们的研究，以了解母乳中的这些非抗体成分对我们观察到的轮状病毒疫苗中和活性的具体贡献。母乳样本采集自印度（N = 40）、南非（N = 50）和美国（N = 51）4 - 29周龄（即疫苗合格年龄）母乳喂养婴儿的母亲。我们使用酶免疫测定法、空斑减少测定法或微量中和测定法检测了母乳中的乳铁蛋白、乳凝集素、轮状病毒特异性伊加和对3种轮状病毒疫苗株（Rotarix、RotaTeq G1和116 E）的中和活性。我们观察到较高水平的乳铁蛋白，lactadherin，伊加和中和活性的母乳标本从印度和南非的妇女比那些从美国妇女。我们证明了印度和南非样本中乳铁蛋白或伊加水平与中和活性之间的正相关，但在美国样本中没有。我们证明了乳铁蛋白的抑制作用是剂量或物种依赖性的，如人乳铁蛋白对Rotarix和116 E滴度的更大降低所证明的。Lactadherin也表现出对轮状病毒疫苗的抑制活性，但似乎不太有效。轮状病毒疫苗在发展中国家的免疫原性和有效性较低，部分原因是婴儿在接种时母乳中高水平抗体和非抗体成分的协同抑制作用。因此，需要在母乳喂养人群中采用替代轮状病毒疫苗策略。
Live oral rotavirus vaccines have been less immunogenic and efficacious for children of developing countries than for those in middle income and industrialized countries, and the basis for these differences is not fully understood. Recently, we demonstrated that breastmilk from mothers in India had significantly higher IgA and neutralizing activity against rotavirus that could reduce the effective titer of rotavirus vaccines reaching the gut when compared with that from mothers in the United States. We extended our study to understand the specific contribution of those nonanti-body components in breastmilk to the neutralizing activity against rotavirus vaccine we observed. Breastmilk samples were collected from mothers of breastfeeding infants aged between 4 and 29 weeks (ie, vaccine eligible age) in India (N = 40), South Africa (N = 50) and the United States (N = 51). We examined breastmilk for lactoferrin, lactadherin, rotavirus-specific IgA and neutralizing activity against 3 rotavirus vaccine strains (Rotarix, RotaTeq G1 and 116E) using enzyme immunoassays, a plaque reduction assay or a microneutralization assay. We observed higher levels of lactoferrin, lactadherin, IgA and neutralizing activity in breastmilk specimens from Indian and South African women than those from American women. We demonstrated positive associations between levels of lactoferrin or IgA and neutralizing activity in Indian and South African specimens, but not in American specimens. We demonstrated that the inhibitory effect of lactoferrin was dose- or species-dependent, as evidenced by greater reduction in titer of Rotarix and 116E by human lactoferrin. Lactadherin also exhibited inhibitory activity to rotavirus vaccines but appeared to be less effective. The lower immunogenicity and efficacy of rotavirus vaccines in developing countries could be explained, in part, by synergistic inhibitory effect of high levels of antibody and nonantibody components in breastmilk consumed by infants at the time of immunization. Therefore, there is a need for alternative rotavirus vaccine strategies in breast-feeding populations.