Heterologous Effects of Pertussis and Influenza Vaccines During Pregnancy on Maternal and Infant Innate Immune Responses A Pilot Study

Background: Research has demonstrated that some vaccines may have effects on the immune system beyond their intended targets. These heterologous effects of vaccination occur through reprogramming of innate immune cells, resulting in enhanced cytokine responses to unrelated pathogens and have been observed most evidently following Bacillus Calmette-Guerin vaccination. Pregnant women in the United Kingdom are offered influenza and acellular pertussis (Tdap) vaccines to protect the mother and infant, respectively, from infection. Little is known about the potential heterologous effects of vaccines given during pregnancy on the maternal and infant immune systems. Objective: To investigate heterologous innate immune responses in mothers and infants from pertussis-vaccinated and pertussis/influenza double-vaccinated pregnancies compared with unvaccinated pregnancies, in a pilot cohort. Methods: In this pilot study, samples collected as part of 2 maternal immunization studies were utilized. Maternal and cord peripheral blood mononuclear cells (PBMCs) were collected at birth from women who had received both Tdap and influenza vaccination, only the Tdap vaccine or no vaccines during pregnancy. To further investigate the effect of influenza vaccination alone, PBMCs were collected from nonpregnant women before and after seasonal influenza vaccination. PBMCs were incubated with pattern recognition receptor (PRR) ligands, vaccine adjuvants or CRM197 for 24 hours and cytokine responses were quantified in supernatants by enzyme-linked immunosorbent assay. Results: PBMC from women who received both Tdap and influenza vaccines had reduced IL-1 beta, IL-6 and IL-8 cytokine responses to PRR ligand stimulation, compared with those from women who received Tdap alone. Maternal vaccine status during pregnancy did not impact cytokine responses to PRR stimulation in cord PBMCs. Seasonal influenza vaccination did not alter cytokine responses to PRR ligands in nonpregnant women. Conclusions: Our pilot study suggests that PBMC from women receiving combined Tdap and influenza vaccination during pregnancy may have reduced in vitro cytokine responses to nonpertussis stimuli. Larger cohorts of mother-infant pairs need to be studied to confirm these findings, study the potential mechanisms and control for potential confounders.