Vaccine-Induced Antipertussis Antibodies in Breast Milk
Vaccine-Induced Antipertussis Antibodies in Breast Milk
Background Pertussis vaccination during pregnancy or immediately after delivery is a strategy that is increasingly being recommended to protect young infants from disease. Breast milk contains disease-specific antibodies that can contribute to the protection of young infants. The composition of breast milk could be altered by vaccination during pregnancy or near delivery. However, the quantification of these antibodies in breast milk lacks standardization.
Methods In this paper, sample preparation procedures and detection methods for total and antipertussis toxin (anti-PT) secretory immunoglobulin (sIg) A are proposed that can be accurately repeated and are in accordance with European Medicines Agency and Food and Drug Administration requirements. Both antibody analytes were measured in breast milk samples of lactating women obtained 8–9 weeks postpartum to compare different maternal pertussis vaccination strategies: vaccination during pregnancy, shortly after or at delivery (cocoon), less than 5 years before delivery or more than 5 years before delivery.
Results The validated immunoassays could quantitatively detect total and anti-PT sIgA in the processed breast milk samples. Significantly higher levels of anti-PT sIgA were measured in breast milk after pertussis vaccination during pregnancy or at delivery [geometric mean concentration (GMC): 2.56 and 2.15 IU/mg] in contrast to mothers with no recent (>5 years) pertussis vaccination (GMC: 0.96 IU/mg; P = 0.014 and P = 0.028).
Conclusion Vaccination against pertussis in the second/third trimester of pregnancy or immediately postpartum significantly increased the levels of anti-PT sIgA in breast milk.
In several industrialized countries with long-standing and successful infant vaccination programs, pertussis has become an increasing health problem, particularly in young vulnerable infants, who are too young to be protected by current infant vaccination programs. As a result of epidemiological changes, some countries have decided to implement additional recommendations for pertussis vaccination, such as additional booster doses in adolescents and adults, the cocoon strategy (ie, vaccinating adults that are in regular contact with newborns and young infants) and vaccination during pregnancy (gestational vaccination), to reduce the number of (severe) pertussis cases in young infants (eg, in United States, United Kingdom and Belgium). Since September 2013, pregnant women in Belgium have been recommended to receive a booster vaccination against pertussis during each pregnancy between 24 and 32 weeks of gestation; if this vaccination was missed, a pertussis booster vaccination is offered immediately at or soon after delivery (as part of the cocoon vaccination strategy).
Human breast milk contains a variety of components that positively influence the nutritional status, general development and overall health of newborns and young infants. The World Health Organization recommends colostrum within the first hours of life and exclusive breastfeeding up to the age of 6 months. Breast milk contains several classes of immunoglobulins (Ig): IgG, secretory Ig (sIg) M and sIgA, the latter being the predominant Ig in breast milk. These sIgA antibodies are secreted into the lumens of mucosal organs and can provide protection to the infant by binding pathogenic microorganisms, thereby inhibiting the invasion and colonization of the mucosal membranes. Disease-specific sIgA antibodies are able to bind microorganisms directly, although the Fc part of the sIgA molecule can bind bacterial carbohydrates; sIgA functions as a first-line barrier to protect the epithelium from pathogens and toxins. Maternal vaccination (during pregnancy as well as immediately after delivery) can increase the amount of specific sIgA transmitted through breast milk, which was recently shown for pertussis vaccination during pregnancy by Abu Raya et al.
A thorough literature survey demonstrated that no detection methods for the measurement of sIgA against vaccine-preventable diseases in breast milk have been thoroughly validated. In general, data on pre-analytical procedures for breast milk are rather scarce. Well-validated assays are needed to generate accurate data that can be easily compared among laboratories. An ongoing study on pertussis vaccination in pregnant women in Belgium (clinicaltrials.gov NCT01698346) offered the opportunity to validate commercial immunoassays and to analyze the influence of different maternal vaccination strategies on total sIgA and anti-Bordetella pertussis toxin sIgA in breast milk.
Abstract and Introduction
Abstract
Background Pertussis vaccination during pregnancy or immediately after delivery is a strategy that is increasingly being recommended to protect young infants from disease. Breast milk contains disease-specific antibodies that can contribute to the protection of young infants. The composition of breast milk could be altered by vaccination during pregnancy or near delivery. However, the quantification of these antibodies in breast milk lacks standardization.
Methods In this paper, sample preparation procedures and detection methods for total and antipertussis toxin (anti-PT) secretory immunoglobulin (sIg) A are proposed that can be accurately repeated and are in accordance with European Medicines Agency and Food and Drug Administration requirements. Both antibody analytes were measured in breast milk samples of lactating women obtained 8–9 weeks postpartum to compare different maternal pertussis vaccination strategies: vaccination during pregnancy, shortly after or at delivery (cocoon), less than 5 years before delivery or more than 5 years before delivery.
Results The validated immunoassays could quantitatively detect total and anti-PT sIgA in the processed breast milk samples. Significantly higher levels of anti-PT sIgA were measured in breast milk after pertussis vaccination during pregnancy or at delivery [geometric mean concentration (GMC): 2.56 and 2.15 IU/mg] in contrast to mothers with no recent (>5 years) pertussis vaccination (GMC: 0.96 IU/mg; P = 0.014 and P = 0.028).
Conclusion Vaccination against pertussis in the second/third trimester of pregnancy or immediately postpartum significantly increased the levels of anti-PT sIgA in breast milk.
Introduction
In several industrialized countries with long-standing and successful infant vaccination programs, pertussis has become an increasing health problem, particularly in young vulnerable infants, who are too young to be protected by current infant vaccination programs. As a result of epidemiological changes, some countries have decided to implement additional recommendations for pertussis vaccination, such as additional booster doses in adolescents and adults, the cocoon strategy (ie, vaccinating adults that are in regular contact with newborns and young infants) and vaccination during pregnancy (gestational vaccination), to reduce the number of (severe) pertussis cases in young infants (eg, in United States, United Kingdom and Belgium). Since September 2013, pregnant women in Belgium have been recommended to receive a booster vaccination against pertussis during each pregnancy between 24 and 32 weeks of gestation; if this vaccination was missed, a pertussis booster vaccination is offered immediately at or soon after delivery (as part of the cocoon vaccination strategy).
Human breast milk contains a variety of components that positively influence the nutritional status, general development and overall health of newborns and young infants. The World Health Organization recommends colostrum within the first hours of life and exclusive breastfeeding up to the age of 6 months. Breast milk contains several classes of immunoglobulins (Ig): IgG, secretory Ig (sIg) M and sIgA, the latter being the predominant Ig in breast milk. These sIgA antibodies are secreted into the lumens of mucosal organs and can provide protection to the infant by binding pathogenic microorganisms, thereby inhibiting the invasion and colonization of the mucosal membranes. Disease-specific sIgA antibodies are able to bind microorganisms directly, although the Fc part of the sIgA molecule can bind bacterial carbohydrates; sIgA functions as a first-line barrier to protect the epithelium from pathogens and toxins. Maternal vaccination (during pregnancy as well as immediately after delivery) can increase the amount of specific sIgA transmitted through breast milk, which was recently shown for pertussis vaccination during pregnancy by Abu Raya et al.
A thorough literature survey demonstrated that no detection methods for the measurement of sIgA against vaccine-preventable diseases in breast milk have been thoroughly validated. In general, data on pre-analytical procedures for breast milk are rather scarce. Well-validated assays are needed to generate accurate data that can be easily compared among laboratories. An ongoing study on pertussis vaccination in pregnant women in Belgium (clinicaltrials.gov NCT01698346) offered the opportunity to validate commercial immunoassays and to analyze the influence of different maternal vaccination strategies on total sIgA and anti-Bordetella pertussis toxin sIgA in breast milk.
