Paediatrics (RCH) - Research Publications

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    Biological sex influences antibody responses to routine vaccinations in the first year of life
    Zimmermann, P ; Perrett, KP ; Ritz, N ; Flanagan, KL ; Robins-Browne, R ; van der Klis, FRM ; Curtis, N ; Abruzzo, V ; Allen, K ; Bonnici, R ; Casalaz, D ; Elborough, H ; Freyne, B ; Gardiner, K ; Germano, S ; Kollmann, T ; Messina, N ; Morrison, C ; Nakaya, H ; Ponsonby, AL ; Shann, F ; South, M ; Vuillermin, P (WILEY, 2020-01)
    AIM: We investigated the effect of early-life factors, namely sex, delivery mode, feeding method and antibiotic exposure, on antibody responses to routine vaccinations administered during the first year of life. METHODS: One and seven months after the primary course of routine vaccines and 1 month after routine vaccines at 12 months of age, antibodies against 26 vaccine antigens were measured in 398 healthy infants. The geometric mean concentration (GMC) of antibodies (adjusted for effect modifiers with multiple linear regression) and the seroprotection rate for each vaccine were compared for each early-life factor. RESULTS: Sex had an influence on GMCs. Antibody concentrations were significantly lower at 7 months of age in females for tetanus and filamentous haemagglutinin and at 13 months of age for pertactin. In contrast, at 13 months of age, antibody concentrations were significantly higher in females for polio type 3, pneumococcal serotype 6A and measles. Sex did not have an influence on seroprotection rates. Delivery mode, feeding method and antibiotic exposure did not exert a substantial influence on vaccine antibody concentrations. CONCLUSION: There is a difference between males and females in the humoral response to routine vaccinations in the first year of life.
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    Correlation of Vaccine Responses
    Zimmermann, P ; Ritz, N ; Perrett, KP ; Messina, NL ; van der Klis, FRM ; Curtis, N (FRONTIERS MEDIA SA, 2021-04-02)
    INTRODUCTION: The humoral response to vaccinations varies widely between individuals. There is no data available on the correlation between responses to different vaccines. In this study, we investigated the correlation of antibody responses between routine vaccine antigens in infants. METHODS: One and seven months after the 6-month vaccinations and one month after the 12-month vaccinations, antibody concentrations to diphtheria, tetanus, pertussis, polio (serotypes 1-3), Haemophilus influenzae type b (Hib), pneumococcus (13 serotypes), meningococcus C, measles, mumps and rubella were measured using fluorescent bead-based multiplex immune-assays. For the correlation of antibody responses, Spearman's rank correlation coefficients (ρ) with 95% confidence intervals (CI) were calculated between responses to each vaccine antigen. RESULTS: The correlation between concentrations of antibodies to the vaccinations ending at 6 months of age was higher one month compared to seven months after vaccination. The strongest correlations at both time points were observed between antibody responses to different polio serotypes, certain pneumococcal serotypes and between responses to diphtheria and pneumococcal (conjugated to a diphtheria toxoid) vaccine antigens. Correlation between responses to tetanus, Hib, pertussis, polio and other vaccine antigens were weak. The correlation between antibody responses to the 12-month vaccine antigens was weaker than to the 6-month vaccine antigens and there was a negative correlation between responses to measles, mumps, rubella vaccine and non-live vaccine antigens (meningococcus C, tetanus and Hib). There was only weak correlation between antibody responses to vaccines of the same type (e.g. conjugated polysaccharide or toxoid vaccines). CONCLUSION: Correlation between antibody responses to similar antigens in the same vaccine (such as different serotypes of a bacteria or virus), as well as responses to antigens conjugated to similar carrier proteins, are strong. In contrast, correlation between responses to other vaccines are weak. Measuring antibody responses to one or a few vaccine antigens therefore does not offer a reliable surrogate marker of responses to unrelated vaccines.
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    The Effect of Maternal Immunisation During Pregnancy on Infant Vaccine Responses
    Zimmermann, P ; Perrett, KP ; Messina, NL ; Donath, S ; Ritz, N ; van der Klis, FRM ; Curtis, N (ELSEVIER, 2019-08)
    INTRODUCTION: Immunisation during pregnancy to protect infants against tetanus, pertussis and influenza is recommended in many countries. However, maternal antibodies can interfere with infant vaccine responses. We investigated the effect of antenatal diphtheria-tetanus-acellular pertussis (dTpa) and trivalent inactivated influenza (TIV) immunisation on specific and heterologous antibody responses to routine immunisations given in the first year of life. METHODS: In total, 471 healthy infants were included. At 7 and 13 months of age, antibodies to the primary course of routine vaccines given at 6 weeks, 4 and 6 months of age (pertussis (pertussis toxin (PT), filamentous haemagglutinin (FHA), pertactin (PRN)), polio (type 1, 2, 3), Haemophilus influenzae type b (Hib), pneumococcus (serotype 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F)) were measured, and at 13 months of age, antibodies to the 12-month routine vaccines (Hib, meningococcus C, measles, mumps and rubella). The seroprotection rates for each vaccine and the geometric mean concentrations (GMC) of antibodies were compared between infants whose mothers did or did not receive dTpa or TIV immunisation during pregnancy. RESULTS: A total of 369 infants were included in the final analysis. Maternal dTpa immunisation was associated with reduced antibody responses to both specific (diphtheria and pertussis) and heterologous (polio and pneumococcus) vaccine antigens. This effect was stronger for persistence of antibodies at 13 months of age than it was at 7 months of age. At 7 months of age, adjusted average antibody concentrations were significantly lower for diphtheria, pertussis (PT, FHA, PRN) and polio type 2, and at 13 months of age, for diphtheria, pertussis (PT, FHA, PRN), polio type 1-3 and pneumococcal serotypes 1, 4, 5, 6A, 6B, 7F, 18C and 23F. Additionally, at 13 months of age, seroprotection rates for diphtheria, PT, pneumococcal serotype 1, 6A and 6B were significantly lower in infants after maternal dTpa immunisation. In contrast, for Hib, in infants with maternal dTpa immunisation, the adjusted average antibody concentration and the seroprotection rate were higher, particularly at 7 months of age. Maternal TIV immunisation had minimal effect on infant vaccine responses. CONCLUSION: Whilst maternal immunisation protects infants in the first few months of life, it might interfere with both specific and heterologous (unrelated) vaccines responses in infants. RESEARCH IN CONTEXT: Evidence before this study: Maternal immunisation during pregnancy helps to protect infants during the period before they complete their primary immunisations. It has been proven to be safe and beneficial. However, pre-existing maternal antibodies can influence antibody responses following infant immunisation, an effect called 'blunting'. Previous studies have investigated the influence of dTpa but not influenza immunisation during pregnancy on infant vaccine responses. The majority of studies investigated antibody concentrations only to the specific vaccine antigens included in the maternal immunisation, and there is scarce data available on heterologous vaccine responses, particularly pneumococcal responses.Added value of this study: In this study, we have shown that maternal dTpa immunisation during pregnancy is associated with reduced antibody responses to both specific (diphtheria and pertussis) and heterologous (polio and pneumococcus) vaccine antigens. This effect is stronger for persistence of antibodies at 13 months of age than after primary immunisation at 7 months of age. In contrast, for Hib, in infants with maternal dTpa immunisation, antibody concentrations are higher, particularly at 7 months of age. Maternal TIV immunisation has minimal effect on infant vaccine responses.Implications of all the available evidence: Whilst maternal immunisation protects infants in the first few months of life, it might interfere with both specific and heterologous (unrelated) vaccines responses in infants. As most vaccines induce very high antibody responses, small differences in antibody concentrations may not be of clinical significance. However, since maternal immunisation during pregnancy also influences seroprotection rates, strategies, such as additional booster doses in the second year of life, particularly for pertussis and pneumococcus, might need to be considered to address this.