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.
Keywords: Adacel; Antibodies; BCG, Bacillus Calmette-Guérin vaccine; Boostrix; CI, confidence interval; FHA, filamentous haemagglutinin; FIM, fimbriae; Flu; GMC, geometric mean antibody concentration; GMR, geometric mean antibody ratio; HepB, hepatitis B; Heterologous; Hib, Haemophilus influenzae type b; Humoral; IPV, inactivated polio vaccine; IgG, immunoglobulin G; Immunisation; Immunoglobulin; Influenza; MIS BAIR, Melbourne Infant Study: BCG for Allergy and Infection Reduction; MMR, measles-mumps-rubella vaccine; MenC, meningococcus type C; Non-specific; PCV13, 13-valent conjugate pneumococcal vaccine; PRN, pertactin; PT, pertussis toxin; TCV, tetanus-containing vaccine; TIV, trivalent inactivated influenza vaccine; Titre; Vaccination; dTpa; dTpa, diphtheria-tetanus-acellular pertussis vaccine.