Newborns of mothers vaccinated against pertussis (whooping cough) during pregnancy have antibodies not only in their blood but also in their nasal membranes, the entry site for Bordetella pertussis, the bacteria that cause the highly contagious disease, a phase 4 randomized controlled trial shows for the first time.

The Gambian Pertussis Study Team conducted the immunologic vaccine substudy among healthy pregnant women and their 160 infants at a single center in Gambia from February 2019 to May 2021. The women, who were aged 18 to 40 years, were randomly assigned to receive an inactivated tetanus, diphtheria, acellular pertussis, and poliovirus (Tdap–IPV) vaccine or a tetanus-toxoid (TT)-only vaccine at 28 to 34 weeks’ gestation.

Their infants were randomly assigned in a 1:1 ratio to receive the primary three-dose series consisting of either a diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccine or a diphtheria, tetanus, acellular pertussis (DTaP) vaccine at ages 8, 12, and 16 weeks. 

The investigators used nasosorption devices to collect nasal mucosal lining fluid (MLF) from infants at ages 8, 16, 17, and 20 weeks and at 9 months. Outcomes were levels of nasal anti-B pertussis immunoglobin G (IgG) and immunoglobulin A (IgA) and anti-pertussis toxin IgG before and after receipt of the DTaP or DTwP primary immunization series at ages 8 and 20 weeks and 9 months and levels of nasal T-cell–related cytokines at age 17 weeks.

“Mucosal protection against pertussis depends on antibodies and the activation of mucosal-resident memory T cells, both of which are differentially induced by acellular pertussis and whole-cell pertussis vaccines,” the study authors wrote.

The findings were published last week in The Lancet Microbe.

Broad nasal cytokine responses after whole-cell vaccination 

Before primary vaccination, 8-week-old infants born to mothers who received the Tdap–IPV vaccine during pregnancy had higher concentrations of maternally derived nasal anti–pertussis toxin IgG (geometric mean ratio [GMR], 3.84) and anti–B pertussis IgG (GMR, 6.45)—but not IgA—than infants whose mothers were given the TT vaccine. 

After receipt of the primary vaccination series, both groups of infants who received the DTwP vaccine had significantly higher geometric mean concentrations (GMCs) of nasal anti–B pertussis IgG than infants given the DTaP vaccine (5.42 arbitrary units per milliliter [AU/mL] for the TT–DTwP group and 4.40 AU/mL for the Tdap–IPV–DTwP group, versus 2.16 AU/mL for the Tdap–IPV–DTaP group). 

In addition, the DTaP-vaccinated infants of mothers who received the Tdap–IPV vaccine during pregnancy had the lowest anti–B pertussis IgG concentrations—even those who had low levels of maternally derived antibodies before vaccination.

Likewise, relative to TT vaccination, Tdap–IPV vaccination during pregnancy was tied to lower nasal anti-pertussis toxin IgG responses in 20-week-old infants after completion of the DTwP and DTaP primary immunization series. 

This blunting effect, however, was more evident after DTwP receipt (GMC, 0.016 IU/mL for Tdap–IPV–DTwP, compared with 0.073 IU/mL for TT–DTwP and 0.021 IU/mL for Tdap–IPV–DTaP versus 0.058 IU/mL for the TT–DTaP group). Broad nasal T-cell–linked cytokine responses were noted after primary immunization in infants vaccinated with DTwP but not DTaP, with no apparent effects from the vaccine given in pregnancy.

Acellular vaccines provide shorter-term protection

“We knew that maternal antibodies are passed on by way of the placenta,” senior study author Beate Kampmann, MD, PhD, of Charite Universitatsmedizin in Berlin, said in a Charite news release. “We were surprised, however, to find that we could also detect them in the nasal mucosa of newborns—in a manner that is gentle on the children. This underlines the effectiveness of indirect vaccination.”