Prevaccination Rotavirus Serum IgG and IgA Are Associated With Lower Immunogenicity of Live, Oral Human Rotavirus Vaccine in South African Infants
Prevaccination Rotavirus Serum IgG and IgA Are Associated With Lower Immunogenicity of Live, Oral Human Rotavirus Vaccine in South African Infants
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DOI：
10.1093/cid/civ828
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发表时间：
2016-01-15
影响因子：
11.8
通讯作者：
Madhi, Shabir A.
中科院分区：
文献类型：
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作者：
Moon, Sung-Sil;Groome, Michelle J.;Madhi, Shabir A.
背景口服轮状病毒（RV）活疫苗在非洲国家的儿童中显示出适度的疗效，原因尚不完全清楚。我们检测了预先存在的抗轮状病毒抗体对单价RV疫苗（RV 1）免疫原性的可能抑制作用。在南非索韦托，当婴儿5-8周龄时，在常规免疫接种访视时登记母婴对。在RV 1第一次和第二次给药前以及第二次给药后1个月获得婴儿血清样品。在对婴儿给予每个剂量的RV 1之前获得母体血清和母乳样品。RV特异性免疫球蛋白G（IgG），伊加，和中和活性的婴儿血清和血清或母乳样品的母亲使用酶联免疫吸附试验或微量中和试验。在入组时RV伊加血清阴性的107对婴儿血清中，我们观察到婴儿和母亲第1次给药前血清中IgG滴度之间存在强正相关，婴儿第1次给药前血清中IgG滴度与第1次给药后RV 1血清转化之间存在显著负相关。同样，RV 1后婴儿伊加血清转化的母亲血清中第1次给药前IgG滴度显著低于婴儿未血清转化的母亲。高水平的既存血清IgG，包括经胎盘获得的母体IgG，似乎对婴儿中RV 1的免疫原性具有抑制作用，并且可能部分导致RV疫苗在这种和其他低收入环境中的有效性降低。
Background. Live oral rotavirus (RV) vaccines have shown modest efficacy among children in African countries for reasons that are not completely understood. We examined the possible inhibitory effect of preexisting antirotavirus antibodies on immunogenicity of monovalent RV vaccine (RV1).Methods. Mother-infant pairs were enrolled at presentation for their routine immunization visit in Soweto, South Africa, when infants were aged 5-8 weeks. Infant serum samples were obtained before the first and second doses of RV1 and 1 month after the second dose. Maternal serum and breast milk samples were obtained prior to administration of each dose of RV1 to infants. RV-specific immunoglobulin G (IgG), IgA, and neutralizing activity in sera of infants and serum or breast milk samples of mothers were measured using enzyme-linked immunosorbent assays or a microneutralization test.Results. Of the 107 serum pairs from infants who were seronegative for RV IgA at enrollment, we observed a strong positive association between IgG titers in pre-dose 1 sera of infants and mothers and significant negative associations between IgG titers in pre-dose 1 sera of infants and seroconversion to RV1 post-dose 1. Similarly, mothers whose infants' IgA seroconverted after RV1 had significantly lower pre-dose 1 IgG titers in sera than those whose infants did not seroconvert.Conclusions. High levels of preexisting serum IgG, including transplacentally acquired maternal IgG, appeared to have an inhibitory effect on the immunogenicity of RV1 among infants and may, in part, contribute to lower efficacy of RV vaccines in this and other low-income settings.