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The Effect of Maternal Immunisation During Pregnancy on Infant Vaccine Responses.
EClinicalMedicine 2019; 13:21-30E

Abstract

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.

Authors+Show Affiliations

Department of Paediatrics, The University of Melbourne, Parkville, Australia. Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, Australia. Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia. Department of Paediatrics, Fribourg Hospital HFR and Faculty of Science and Medicine, University of Fribourg, Switzerland.Food Allergy Research Group and Melbourne Children's Trial Centre, Murdoch Children's Research Institute, Parkville, Australia. Departments of Allergy and Immunology and General Medicine, Royal Children's Hospital Melbourne, Parkville, Australia. School of Population and Global Health, The University of Melbourne, Parkville, Australia.Department of Paediatrics, The University of Melbourne, Parkville, Australia. Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia.Department of Paediatrics, The University of Melbourne, Parkville, Australia. Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia.Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, Australia. Infectious Diseases Unit, University of Basel Children's Hospital, Basel, Switzerland.Laboratory for Infectious Diseases and Screening, National Institute of Public Health and the Environment, Bilthoven, the Netherlands.Department of Paediatrics, The University of Melbourne, Parkville, Australia. Infectious Diseases Unit, The Royal Children's Hospital Melbourne, Parkville, Australia. Infectious Diseases Research Group, Murdoch Children's Research Institute, Parkville, Australia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31517260

Citation

Zimmermann, Petra, et al. "The Effect of Maternal Immunisation During Pregnancy On Infant Vaccine Responses." EClinicalMedicine, vol. 13, 2019, pp. 21-30.
Zimmermann P, Perrett KP, Messina NL, et al. The Effect of Maternal Immunisation During Pregnancy on Infant Vaccine Responses. EClinicalMedicine. 2019;13:21-30.
Zimmermann, P., Perrett, K. P., Messina, N. L., Donath, S., Ritz, N., van der Klis, F. R. M., & Curtis, N. (2019). The Effect of Maternal Immunisation During Pregnancy on Infant Vaccine Responses. EClinicalMedicine, 13, pp. 21-30. doi:10.1016/j.eclinm.2019.06.010.
Zimmermann P, et al. The Effect of Maternal Immunisation During Pregnancy On Infant Vaccine Responses. EClinicalMedicine. 2019;13:21-30. PubMed PMID: 31517260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Effect of Maternal Immunisation During Pregnancy on Infant Vaccine Responses. AU - Zimmermann,Petra, AU - Perrett,Kirsten P, AU - Messina,Nicole L, AU - Donath,Susan, AU - Ritz,Nicole, AU - van der Klis,Fiona R M, AU - Curtis,Nigel, Y1 - 2019/07/26/ PY - 2019/03/31/received PY - 2019/06/01/revised PY - 2019/06/18/accepted PY - 2019/9/14/entrez PY - 2019/9/14/pubmed PY - 2019/9/14/medline KW - Adacel KW - Antibodies KW - BCG, Bacillus Calmette-Guérin vaccine KW - Boostrix KW - CI, confidence interval KW - FHA, filamentous haemagglutinin KW - FIM, fimbriae KW - Flu KW - GMC, geometric mean antibody concentration KW - GMR, geometric mean antibody ratio KW - HepB, hepatitis B KW - Heterologous KW - Hib, Haemophilus influenzae type b KW - Humoral KW - IPV, inactivated polio vaccine KW - IgG, immunoglobulin G KW - Immunisation KW - Immunoglobulin KW - Influenza KW - MIS BAIR, Melbourne Infant Study: BCG for Allergy and Infection Reduction KW - MMR, measles-mumps-rubella vaccine KW - MenC, meningococcus type C KW - Non-specific KW - PCV13, 13-valent conjugate pneumococcal vaccine KW - PRN, pertactin KW - PT, pertussis toxin KW - TCV, tetanus-containing vaccine KW - TIV, trivalent inactivated influenza vaccine KW - Titre KW - Vaccination KW - dTpa KW - dTpa, diphtheria-tetanus-acellular pertussis vaccine SP - 21 EP - 30 JF - EClinicalMedicine JO - EClinicalMedicine VL - 13 N2 - 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. SN - 2589-5370 UR - https://www.unboundmedicine.com/medline/citation/31517260/The_Effect_of_Maternal_Immunisation_During_Pregnancy_on_Infant_Vaccine_Responses L2 - https://linkinghub.elsevier.com/retrieve/pii/S2589-5370(19)30103-8 DB - PRIME DP - Unbound Medicine ER -