Varun Kishor Phadke, MD is a third-year infectious diseases fellow in the Emory T32 Vaccinology Training Program (VTP). Dr. Phadke works in the areas of vaccine clinical trials and maternal immunization, with a focus on pertussis.
Pertussis is an important cause of morbidity and mortality in infants who are too young to receive the childhood pertussis vaccine (i.e. aged <2 months), especially in developing countries. Maternal immunization against pertussis – administration of pertussis-containing vaccine during pregnancy – takes advantage of the normal transplacental transfer of antibodies to the developing fetus to provide protection to the infant in the first weeks to months immediately after birth. A small number of countries, including the United States, have already adopted a strategy of routine immunization of pregnant women with a pertussis-containing vaccine (tetanus, reduced diphtheria, and acellular pertussis, or Tdap) in order to prevent infant pertussis. Although maternal immunization with Tdap is currently the only viable strategy for protecting newborn infants from pertussis, this intervention has never been evaluated in a prospective clinical trial.
Dr. Phadke is a co-investigator under Saad Omer, MBBS, MPH, PhD on a clinical trial studying maternal immunization against pertussis in Guatemala. Dr. Omer and his team plan to enroll approximately 380 pregnant women and randomize them to receive either Td (Tetanus and reduced diphtheria; the standard of care) or Tdap. The team will then evaluate the immune response of the pregnant women to the vaccines, as well as their infants’ subsequent immune responses to their own childhood pertussis vaccine. In addition, the team will determine the incidence of pertussis in the infants of both groups of women.
They hope to bridge two specific knowledge gaps with this study:
First, it is well known that passively acquired maternal antibodies can interfere with the infant immune response to childhood vaccines. Although high levels of maternal antibodies to pertussis do not seem to substantially affect the infant immune response to acellular pertussis vaccines (used in developed countries), there are some studies that indicate that high levels of maternal antibodies are associated with a reduced infant immune response to whole-cell pertussis vaccines. So the first aim is to determine the impact of maternal immunization with Tdap on the infant’s immune response to whole-cell pertussis vaccine. This will help guide the implementation of maternal Tdap in countries that use whole-cell vaccine in the childhood schedule (such as Guatemala).
Next, gender-specific differences in vaccine-induced immune responses have been well-described, but there have only been a small number of studies that have specifically compared pregnant and non-pregnant women. Since maternal immunization is increasingly being recognized as a strategy for protecting young infants from a variety of vaccine-preventable diseases (not just pertussis), a better understanding of the effect of pregnancy on vaccine-induced immune responses is needed. The second aim is to learn more about the effect of pregnancy on the immune response to vaccines. This will help guide the optimal timing and dose of vaccines during pregnancy, as well as provide a foundation for rational vaccine design in this population.