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Rotavirus-specific IgG Antibodies From Mothers’ Serum May Inhibit Infant Immune Responses to the Pentavalent Rotavirus Vaccine

2014; Lippincott Williams & Wilkins; Volume: 34; Issue: 1 Linguagem: Inglês

10.1097/inf.0000000000000481

1532-0987

Sylvia Becker‐Dreps, Samuel Vilchez, Daniel E. Velásquez, Sung-Sil Moon, Michael G. Hudgens, Luis Enrique Zambrana, Baoming Jiang,

Congenital Anomalies and Fetal Surgery

To the Editors: Rotavirus vaccines have lower effectiveness in low and middle income countries. One possible explanation is vaccine inhibition by rotavirus-specific antibodies present in mothers' sera or breast milk. IgG antibodies in maternal sera are transferred through the placenta and may inhibit vaccine-elicited immune responses, as recently reported for the 116E rotavirus vaccine.1 Also, breast milk IgA and neutralizing antibodies may directly inhibit the oral vaccine upon administration.2,3 Breast milk from low and middle income country mothers has higher levels of rotavirus-specific antibodies as compared with mothers from high income countries,3,4 indicating a greater potential for inhibition. The authors examined the association between rotavirus-specific antibodies in maternal sera and breast milk and immunogenicity to the first dose of the pentavalent rotavirus vaccine (RV5, Rotateq [Merck Sharp & Dohme]) in respective infants. Mother–infant pairs were recruited in León, Nicaragua in 2012. Eligibility criteria included normal birth weight, gestational age >35 weeks, currently breastfeeding ≥4 times daily, and mother and infant without known immune disorder or blood transfusion. The authors measured rotavirus-specific antibodies in maternal and infant serum at the time of RV5 immunization, and in infant serum 4 weeks following the first dose (postdose 1) by enzyme-linked immunosorbent assays.2,4 Breast milk samples of mothers collected at the time of immunization were assayed for rotavirus-specific IgA and neutralizing antibodies.2 For IgA and IgG assays, the authors started dilutions at 1:10, whereas for breast milk neutralizing antibody assays, they started dilutions at 1:2. Preimmunization seropositivity was defined as preimmunization rotavirus-specific IgA titers ≥40.5 Seroconversion was defined as a≥4-fold increase in rotavirus-specific IgA titers in the infant between the preimmunization and postdose 1 serum samples. Spearman's rank correlation coefficients were estimated to examine associations between rotavirus-specific IgG antibodies in maternal serum and infant preimmunization serum. Wilcoxon rank-sum tests were used to compare antibody titers between groups. The 45 infants enrolled had a median preimmunization rotavirus-specific IgA titer of 10 and a postdose 1 titer of 80. Among all the infants, 22.2% were seropositive prior to immunization. There was a positive association between rotavirus-specific IgG titers in maternal serum and preimmunization infant serum (r = 0.57, P < 0.0001). Sixty-nine percent of infants met the seroconversion definition postdose 1. Infants who did not seroconvert had mothers with higher serum rotavirus-specific IgG titers as compared with mothers of infants who did seroconvert (median 5120 in nonseroconverters vs. 2560 in seroconverters, P = 0.02) (Table 1). Also, seroconversion occurred among 30% of infants who were IgA seropositive prior to immunization versus 80% of infants who were not IgA seropositive prior to immunization (P = 0.005). There was no significant difference in breast milk rotavirus-specific IgA titers between infants who did and did not seroconvert, although the sample size may not have been large enough to detect a small difference.TABLE 1: Comparison of Baseline Rotavirus-specific Antibody Titers Between Infants Who Seroconverted* and Infants Who Did Not Seroconvert (median Titers [Interquartile Ranges])This study suggests that high titers of maternal rotavirus-specific IgG antibodies at the time of immunization may inhibit RV5-elicited immune responses. It is unclear whether these infants will be protected through active immunization from the remaining RV5 doses. Also, infants who were IgA seropositive prior to immunization were less likely to seroconvert. The clinical importance of preimmunization IgA seropositivity in terms of vaccine immunogenicity and protection from rotavirus disease warrants further investigation. SylviaBecker-Dreps, MD, MPH Department of Family Medicine School of Medicine University of North Carolina at Chapel Hill Chapel Hill, NC SamuelVilchez, PhD Department of Microbiology and Parasitology Faculty of Medical Sciences National Autonomous University of Nicaragua León, Nicaragua DanielVelasquez, MSc Sung-SilMoon, PhD Gastroenteritis and Respiratory Viruses Laboratory Branch Division of Viral Diseases Centers for Disease Control and Prevention Atlanta, GA Michael G.Hudgens, PhD Department of Biostatistics Gillings School of Global Public Health University of North Carolina at Chapel Hill Chapel Hill, NC Luis EnriqueZambrana, MD, MPH Center for Epidemiology and Health National Autonomous University of Nicaragua, León, Nicaragua BaomingJiang, DVM, PhD Gastroenteritis and Respiratory Viruses Laboratory Branch Division of Viral Diseases Centers for Disease Control and Prevention Atlanta, GA