Profiling the dynamics of maternally acquired and infection-induced antibodies against influenza B in early childhood: a longitudinal paired mother-infant cohort study from southern China.

Abstract

Influenza B virus infection can cause clinical outcomes that are as severe as those caused by influenza A in young children. However, the early-life immunological trajectory of influenza B remains poorly characterised. We aimed to assess the transplacental transfer and decay of maternal antibodies, and characterise the dynamics and cross-reactivity of infection-induced antibodies in early childhood. Between Sept 20, 2013, and Oct 14, 2015, we enrolled 1054 mothers and their 1066 infants in a prospective cohort study in China. Eligible participants were mothers who delivered at the study sites and provided written informed consent for themselves and their infants. Among these individuals, 531 mothers and their 534 neonates were selected for the present analysis via stratified random sampling. Maternal venous and cord blood were collected at delivery, with follow-up serum samples from children at 2, 4, 6, 12, 24, and 36 months and at 5-8 years. Haemagglutination inhibition assays measured titres against four B/Victoria and two B/Yamagata strains. We assessed the transplacental transfer efficiency and the half-life as well as the time-to-loss of maternal antibodies and characterised the kinetics and cross-reactivity of influenza B infection-induced antibodies from birth to 5-8 years. Maternal antibodies were efficiently transferred (mean transfer ratio 0·9-1·0), and neonatal antibody titres were strongly correlated with maternal titres (r>0·8, p<0·0001). At birth, neonatal seropositivity ranged from 28% to 79% for different strains. A two-fold increase in maternal titres was associated with an 84% increase in neonatal titres (95% CI 81-88). Maternal antibody half-lives ranged from 44 days to 48 days, and 50% of infants lost protective antibodies by 2·2-2·5 months. By age 3 years, 30% of children had serological evidence of influenza B infection. Infection risk increased with age (seroincidence was 1% [0-11 months], 12% [12-23 months], 10% [24-35 months], and 15% [36-42 months]; p<0·0001). Higher maternal and child pre-epidemic titres reduced infection risk for the homologous strain (mean adjusted relative risk: 0·45-0·62 for maternal titres and 0·46-0·56 for child titres; p<0·01). Following infection, children's titres rose to geometric mean titres of 46-56. Infection-induced antibody responses were stronger against homo-lineage strains than against hetero-lineage strains. These findings highlight the transient nature of maternally derived immunity and the suboptimal immunogenicity of influenza B infection in early childhood, underscoring the potential value of maternal vaccination and timely childhood immunisation to bridge the early-life immunity gap. National Natural Science Foundation of China and the Key Program of the National Natural Science Foundation of China.