Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Closed

The effect of timing of gestational Tdap administration on the avidity of pertussis antibodies

Bahaa Abu-Raya, MD, PhD

Summary

BACKGROUND: There is recent worldwide resurgence of pertussis with severe morbidity and mortality among young infants. In an attempt to protect young infants, immunization of all pregnant women against pertussis is currently recommended during 27-36 weeks gestation in a growing number of countries. GAP: The optimal timing of immunization during pregnancy to provide the maximal protection to young infants has not been determined. HYPOTHESIS: Immunization during early 3rd trimester provides the newborns with antibodies with higher avidity as compared to immunization during late 3rd trimester. METHODS: Ammonium thiocyanate was used as a bond-breaking agent to measure the avidity of anti-PT IgG using a range of concentrations between 0.25M (to measure low-avidity antibodies) and 3M (to measure very high-avidity antibodies). Anti-PT IgG levels achieved at each ammonium thiocyanate concentration in newborns of women vaccinated during 28-32 weeks gestation [WG]) vs. 33-36 WG, and between newborns of women vaccinated 5-12 versus 1-4 weeks prior to delivery were compared using t-tests. RESULTS: Newborns of women vaccinated with Tdap during 28-32 WG (n=43) had higher concentrations of medium and high-avidity anti-PT IgG compared with newborns of women vaccinated during 33-36 WG (n=47), 11.6 IU/ml (95% CI, 8.8-15.2) IU/ml vs. 6.7 IU/ml (95% CI, 5.2-8.6) and 10.1 IU/ml (95% CI, 7.4-13.8) vs. 5.7 (95% CI, 3.6-8.9) IU/ml, (p=0.007 and p=0.035), respectively. Newborns of women vaccinated 5-12 weeks prior to delivery (n=64) had higher concentrations of high and very high-avidity anti-PT IgG compared with newborns of women vaccinated within 4 weeks prior to delivery (n=25), 10.3 IU/mL (95% CI, 7.9-13.4) versus 4.3 IU/mL (95% CI, 2.2-8.5), 12.6 IU/mL (95% CI, 9.4-16.9) versus 4.3 IU/mL (95% CI, 2.2-8.5), (all p<0.03), respectively.   IMPACT: Recommending early 3rd trimester immunization will increase immunization opportunities and minimize the bulk of women delivering too early after Tdap receipt. This is of particular relevance for preterm infants who would completely miss out on protection if immunization only occurred in late 3rd trimester.

Publications:

Abu-Raya, Bahaa, Michelle L. Giles, Tobias R. Kollmann, and Manish Sadarangani. "Profiling Avidity of Antibodies Elicited by Vaccination Using Enzyme-Linked Immunosorbent Assay-Based Elution-Insights Into a Novel Experimental and Analytical Approach." Vaccine (2020): S0264-410X.

Abu-Raya, Bahaa, Michelle L. Giles, Tobias R. Kollmann, and Manish Sadarangani. "The Effect of Timing of Tetanus-diphtheria-acellular pertussis Vaccine Administration in Pregnancy on The Avidity of Pertussis Antibodies." Frontiers in Immunology 10 (2019): 2423.

Supervising Institution:
University of British Columbia

Mentors
Tobias Kollmann

Project Location:
Canada

Award Amount:
$25,445