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, 10, 2423
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The Effect of Timing of Tetanus-Diphtheria-Acellular Pertussis Vaccine Administration in Pregnancy on the Avidity of Pertussis Antibodies

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The Effect of Timing of Tetanus-Diphtheria-Acellular Pertussis Vaccine Administration in Pregnancy on the Avidity of Pertussis Antibodies

Bahaa Abu-Raya et al. Front Immunol.

Abstract

Background: Optimal timing of gestational tetanus-diphtheria-acellular pertussis (Tdap) vaccination is not well-defined. No well-established specific anti-pertussis antibody level correlates with protection, suggesting the importance of antibody quality such as avidity. We aimed to determine the effect of timing of vaccination with Tdap in pregnancy on the avidity of cord anti-pertussis toxin (PT) immunoglobulin G (IgG). Methods: Prospective study of newborns in a tertiary hospital (Melbourne, Australia) born to women vaccinated with Tdap in pregnancy. Ammonium thiocyanate was used as a bond-breaking agent to measure the avidity of anti-PT IgG using concentrations between 0.25 M (to measure low avidity antibodies) and 3 M (to measure very high avidity antibodies). Anti-PT IgG levels achieved at each ammonium thiocyanate concentration in cord samples of women vaccinated during 28-32 weeks gestation (WG) vs. 33-36 WG, and women vaccinated 5-12 vs. 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 statistically significant 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 before delivery (n = 64) had statistically significant higher concentrations of high and very high avidity anti-PT IgG compared with newborns of women vaccinated within 4 weeks before delivery (n = 25), 10.3 IU/mL (95% CI, 7.9-13.4) vs. 3.3 IU/mL (95% CI, 1.7-6.4), 12.6 IU/mL (95% CI, 9.4-16.9) vs. 4.3 IU/mL (95% CI, 2.2-8.5) (all p < 0.03), respectively. Conclusions: Quantification of levels of anti-PT IgG with different avidities demonstrated that pertussis vaccination 5-12 weeks before delivery was associated with higher anti-PT IgG avidity compared with vaccination within 4 weeks before delivery. Pertussis vaccination during 28-32 WG was associated with higher anti-PT IgG avidity compared with vaccination during 33-36 WG, supporting vaccination at 28-32 over 33-36 WG for optimal protection against pertussis in infancy.

Keywords: avidity; gestation; immunization; pertussis; pregnancy.

Figures

Figure 1
Figure 1
Fractional absolute anti-PT IgG levels by time of vaccination against pertussis in pregnancy achieved at the different ammonium thiocyanate concentrations. The quantified fractional absolute avidity levels of anti-PT IgG at 0.25 molar (M), 0.5, 1, 1.5, 2, and 3 M of ammonium thiocyanate are classified as low (A), low-medium (B), medium (C), medium-high (D), high (E), and very high (F) avidity anti-PT IgG antibodies, respectively. The horizontal line denotes the cord mean levels in newborns born to unvaccinated women. PT, pertussis toxin; IU/ml, international unit/ml. This figure shows that the earlier Tdap is given in pregnancy the higher fractional absolute levels of low-medium, medium, medium–high, and high avidity anti-PT IgG levels are achieved at birth.
Figure 2
Figure 2
Fractional absolute anti-PT IgG levels by time elapsed from vaccination against pertussis in pregnancy to delivery achieved at the different ammonium thiocyanate concentrations. The quantified fractional absolute avidity levels of anti-PT IgG at 0.25 molar (M), 0.5, 1, 1.5, 2, and 3 M of ammonium thiocyanate are classified as low (A), low-medium (B), medium (C), medium-high (D), high (E), and very high (F) avidity anti-PT IgG antibodies, respectively. The horizontal line denotes the cord mean levels in newborns born to unvaccinated women. PT, pertussis toxin; IU/ml, international unit/ml. This figure shows that the longer the interval between Tdap administration during the third trimester and delivery, the higher the fractional absolute levels of low–medium, medium, medium–high, and high avidity anti-PT IgG achieved at birth.
Figure 3
Figure 3
Distribution of total absolute avidity of anti-PT IgG by timing of vaccination in pregnancy (A) and time elapsed between vaccination and delivery (B). Kernel Density plot shows the total absolute avidity of anti-PT IgG in cord sera of newborns of women vaccinated against pertussis in pregnancy at different times. The density curves were obtained using a Gaussian kernel. PT, pertussis toxin; aP, acellular pertussis; WG, weeks gestation; WK, weeks; IU/ml, international unit/ml; AAU/mL, Absolute Avidity Unit/mL. This figure shows that vaccination with Tdap during 28–32 WG resulted in higher total absolute avidity levels of anti-PT IgG compared with newborns born to women vaccinated during 33–36 WG. Vaccination with Tdap 5–12 weeks prior to delivery resulted in higher cord total absolute avidity levels of anti-PT IgG compared with vaccination within 4 weeks prior to delivery.
Figure 4
Figure 4
Heat-map analysis based on hierarchical unsupervised clustering. Fractional absolute levels of anti-PT IgG with different avidities for 112 cord samples are illustrated. In the heat-map, natural log fractional absolute anti-PT IgG levels are shown by column. The natural log fractional absolute anti-PT IgG levels were color-coded as indicated by the scale in the right, in which levels range from blue to red indicating high (red) and low (blue) levels. Timing of tetanus diphtheria and acellular pertussis (Tdap) administration is displayed by the different rows. PT, pertussis toxin; IU/ml, international unit/ml; WG, weeks gestation; M, molar; wks, weeks. This figure shows that most newborns of women vaccinated during 28–32 WG or more than (or equal to) 5 weeks prior to delivery had an avidity profile consisting of high levels of high fractional absolute anti-PT IgG levels.

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References

    1. CDC Pertussis epidemic–Washington, 2012. MMWR Morb Mortal Wkly Rep. (2012) 61:517–22. - PubMed
    1. Winter K, Harriman K, Zipprich J, Schechter R, Talarico J, Watt J, et al. . California pertussis epidemic, 2010. J Pediatr. (2012) 161:1091–6. 10.1016/j.jpeds.2012.05.041 - DOI - PubMed
    1. Eberhardt CS, Martinez de, Tejada B, Siegrist CA. Reply to Abu Raya et al. Clin Infect Dis. (2016) 63:144–5. 10.1093/cid/ciw235 - DOI - PubMed
    1. Liang JL, Tiwari T, Moro P, Messonnier NE, Reingold A, Sawyer M, et al. Recommendations and reports prevention of pertussis, tetanus, and diphtheria with vaccines in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. (2018) 67:1–42. 10.15585/mmwr.rr6702a1 - DOI - PMC - PubMed
    1. Abu Raya B, Giles M. Timing of prenatal Tdap immunization and protection against pertussis. Clin Infect Dis. (2017) 64:821–2. 10.1093/cid/cix027 - DOI - PubMed

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