Maternal Immunization as a Strategy to Decrease Susceptibility to Infection in Newborn Infants

Benjamin Lindsey; Beate Kampmann; Christine Jones

Disclosures

Curr Opin Infect Dis. 2013;26(3):248-253. 

In This Article

Maternal Vaccination Against Pertussis

The United Kingdom is currently experiencing a severe outbreak of pertussis, similar to that seen in the United States, Canada and Australia. In 2012, there were 9741 cases of pertussis reported in England and Wales, of which 429 were in infants less than 3 months, representing a 10-fold increase in overall notifications since the last peak year in 2008.[24] Of most concern has been the increase in under 3-month old infants, in whom the risk of severe disease, hospitalization and death is high.[25] There have been 14 pertussis-related deaths in infants in 2012, the highest number reported in a year since 2001 and double the number in the last peak year.[24,26] The young infants who died were all too young to have benefited from protection provided by the routine infant immunizations, which start at 2 months of age.

As a response to the increasing rates of pertussis notifications in the United Kingdom, in September 2012 the Department of Health recommended that all pregnant women in the United Kingdom should be offered pertussis vaccination in the third trimester of each pregnancy.[27] In October 2012, the Advisory Committee on Immunization Practices in the USA updated their recommendations to advise that all pregnant women of 27–36 weeks gestation receive pertussis vaccination.[28]

These recommendations have been underpinned by a number of studies. A recent study has demonstrated that waning of pertussis antibodies after immunization prepregnancy or in early pregnancy resulted in low levels of antibody in 2–3-month old infants, such that it was unlikely to provide sufficient protection until infant primary immunizations were complete.[5] This is because antibody levels to pertussis vaccine antigens peak after just 14 days and begin to wane thereafter.[29] Maternal vaccination in the third trimester of pregnancy however is likely to result in high levels in the mother at a time of maximum transplacental transfer of antibody to the infant.

A number of recent studies have demonstrated efficient transplacental transfer of maternal pertussis antibodies.[5,30] Gall et al.[30] demonstrated that cord blood from infants born to mothers who received Tdap in pregnancy had significantly higher pertussis antibody levels than those whose mothers were not vaccinated. Furthermore, interim analysis of an ongoing study has shown that a prepregnancy booster of pertussis vaccine is associated with efficient transplacental transfer of pertussis antibody to the newborn infant and elevated concentrations of antibody in 1-month old infants of vaccinated mothers.[5] However, maternally derived antibody levels wane rapidly in the infant, with a half-life of only 6 weeks.[5,31]

Two randomized, double-blind studies of maternal pertussis vaccines in pregnancy are currently ongoing in the United States and Canada. These studies will assess the safety and immunogenicity of maternal pertussis vaccine and also will evaluate the impact on infant antibody responses to primary vaccination at 2, 4 and 6 months of age.[32,33]

Transplacentally acquired antibodies are likely to confer protection against pertussis in the first weeks of life, however the effectiveness against clinical infection has not yet been shown. Although no serological correlate of protection has been defined against pertussis, higher levels of antibody are thought to provide better protection than low levels.[34] A strong suggestion of benefit can be inferred from other studies showing protection from infection after the infusion of serum containing antipertussis IgG, and through studies showing a correlation of cord antibody levels with protection from pertussis.[35] Following the introduction of a temporary maternal pertussis vaccination programme in the United Kingdom, the effectiveness in terms of reduction of pertussis infection in young infants will be able to be measured.

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