Vaccine 33 (2015) 5490–5491
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Reply to Letter to the Editor The avidity of pertussis antibodies following gestational acellular pertussis immunization: Reply to Maertens Dear Editor, We thank Maertens and colleagues for their insightful comments on the avidity of pertussis antibodies following the immunization of pregnant women with tetanus–diphtheria–acelluarpertussis (Tdap). We recently explored the effect of Tdap immunization during late pregnancy on the relative avidity index (RAI) of umbilical cord immunoglobulin G (IgG) to pertussis toxin (PT) [1]. Our exclusion criteria were devised to minimize natural boosting in order to explore the untainted effect of Tdap immunization on RAI. Our technique was based on Almanzar et al’s publication recommending NH4SCN concentrations lower than 3.0 M as a bond-breaking agent on IgG to PT (Euroimmun Medizinische Labordiagnostika) [2]. Testing variable Chaotropic agent concentrations, 0.06–4.0 M of NH4 SCN, we found 0.25 M to be the optimal concentration in our cohort of women previously primed with whole cell pertussis vaccine. The women immunized with Tdap during late pregnancy had statistically significant higher mean RAI of umbilical cord IgG to PT than those of unimmunized women. Moreover, the RAI of umbilical cord IgG to PT was statistically significant higher for newborns of women immunized at 27–30+6 weeks compared with 31–36 weeks and >36 weeks. The recruited women did not differ significantly in clinical features like age or pertussis exposure/infection history. Moreover, after adjusting for the women’s age, there was still a statistically significant difference in the RAI of umbilical cord IgG to PT of newborns born to Tdap-immunized and unimmunized women (F1,57 = 11.74, p < .001). The Tdap-immunized women at 27–30+6 , 31–36 and >36 weeks did not differ in age, (F2,46 = 2.00, p > .15). Moreover, after adjustment for maternal age, the Tdap-immunized women at 27–30+6 weeks maintained superiority of RAI of IgG to PT compared to the other groups, (F2,45 = 4.62, p < .02). Maertens et al. provides preliminary data from their ongoing trials in Vietnam and Belgium exploring the avidity of maternal antibodies following vaccination with acellular pertussis and found no correlation between the timing of acellular pertussis vaccination and RAI [3]. Different acellular formulations administered to women of different genetic backgrounds may contribute to the different results. Moreover, multiple laboratory variable e.g., temperature, pH the concentration of antibody and duration of incubation also affect the antigen–antibody reaction [4]. Perhaps most importantly, while Maertens and our group used a similar methodology, the use of 0.25 M NH4 SCN dissolved only the low and spared the high avidity http://dx.doi.org/10.1016/j.vaccine.2015.05.090 0264-410X/© 2015 Elsevier Ltd. All rights reserved.
antigen–antibody complexes thereby enhancing our ability to better discriminate between the women according to timing of Tdap administration. Accordingly, in order to obtain the optimal measurement of RAI over a wide range of IgG concentrations, it is of importance to utilize the lowest possible chaotropic agent concentration [5], that will dissolve only the low avidity antigen–antibody complexes to minimize the indiscriminate breaking of all (low and high) antigen–antibody avidity complexes. We hope that future studies from various countries will provide data on the RAI of IgG to PT that will enhance our understanding of the multiple factors, e.g., epidemiology, vaccine coverage, vaccine formulation and timing of Tdap administration to the pregnant involved in antibody avidity. Conflict of interest The authors do not have an association that might pose a conflict of interest. References [1] Abu Raya B, Bamberger E, Almog M, Peri R, Srugo I, Kessel A. Immunization of pregnant women against pertussis: the effect of timing on antibody avidity. Vaccine 2015;(March), http://dx.doi.org/10.1016/j.vaccine.2015.02.059, pii: S0264-410X(15)00248-0. [2] Almanzar G, Ottensmeier B, Liese J, Prelog M. Assessment of IgG avidity against pertussis toxin and filamentous hemagglutinin via an adapted enzyme-linked immunosorbent assay (ELISA) using ammonium thiocyanate. J Immunol Methods 2013;387(1–2):36–42. [3] Leuridan E, Hoang TTH, Maertens K, Nguyen DT, Duong TH, Caboré RN, et al. Pertussis antibody responses in maternal and cord blood samples after vaccination during pregnancy: a Belgian–Vietnamese collaboration. In: Poster 364 Presented at ESPID 2014. 2014. [4] Reverberi R, Reverberi L. Factors affecting the antigen–antibody reaction. Blood Transfus 2007;5(4):227–40. [5] Romero-Steiner S, Holder PF, Gomez de Leon P, Spear W, Hennessy TW, Carlone GM. Avidity determinations for Haemophilus influenzae Type b anti-polyribosylribitol phosphate antibodies. Clin Diagn Lab Immunol 2005;12(9):1029–35.
Bahaa Abu Raya a,b,∗ Department of Pediatrics, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel b The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St. 1, Haifa 31096, Israel
a
Isaac Srugo a,b,c Department of Pediatrics, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel b The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St. 1, Haifa 31096, Israel c Clinical Microbiology Laboratory, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel a
Reply to Letter to the Editor / Vaccine 33 (2015) 5490–5491
Ellen Bamberger a,b The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St. 1, Haifa 31096, Israel b Clinical Microbiology Laboratory, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel a
a
Aharon Kessel a,b The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St. 1, Haifa 31096, Israel b Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel
5491
∗ Corresponding author at: Department of Pediatrics, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel. Tel.: +972 52185125. E-mail address: baha [email protected] (B. Abu Raya)
5 April 2015 Available online 9 June 2015
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Reply to Letter to the Editor The avidity of pertussis antibodies following gestational acellular pertussis immunization: Reply to Maertens Dear Editor, We thank Maertens and colleagues for their insightful comments on the avidity of pertussis antibodies following the immunization of pregnant women with tetanus–diphtheria–acelluarpertussis (Tdap). We recently explored the effect of Tdap immunization during late pregnancy on the relative avidity index (RAI) of umbilical cord immunoglobulin G (IgG) to pertussis toxin (PT) [1]. Our exclusion criteria were devised to minimize natural boosting in order to explore the untainted effect of Tdap immunization on RAI. Our technique was based on Almanzar et al’s publication recommending NH4SCN concentrations lower than 3.0 M as a bond-breaking agent on IgG to PT (Euroimmun Medizinische Labordiagnostika) [2]. Testing variable Chaotropic agent concentrations, 0.06–4.0 M of NH4 SCN, we found 0.25 M to be the optimal concentration in our cohort of women previously primed with whole cell pertussis vaccine. The women immunized with Tdap during late pregnancy had statistically significant higher mean RAI of umbilical cord IgG to PT than those of unimmunized women. Moreover, the RAI of umbilical cord IgG to PT was statistically significant higher for newborns of women immunized at 27–30+6 weeks compared with 31–36 weeks and >36 weeks. The recruited women did not differ significantly in clinical features like age or pertussis exposure/infection history. Moreover, after adjusting for the women’s age, there was still a statistically significant difference in the RAI of umbilical cord IgG to PT of newborns born to Tdap-immunized and unimmunized women (F1,57 = 11.74, p < .001). The Tdap-immunized women at 27–30+6 , 31–36 and >36 weeks did not differ in age, (F2,46 = 2.00, p > .15). Moreover, after adjustment for maternal age, the Tdap-immunized women at 27–30+6 weeks maintained superiority of RAI of IgG to PT compared to the other groups, (F2,45 = 4.62, p < .02). Maertens et al. provides preliminary data from their ongoing trials in Vietnam and Belgium exploring the avidity of maternal antibodies following vaccination with acellular pertussis and found no correlation between the timing of acellular pertussis vaccination and RAI [3]. Different acellular formulations administered to women of different genetic backgrounds may contribute to the different results. Moreover, multiple laboratory variable e.g., temperature, pH the concentration of antibody and duration of incubation also affect the antigen–antibody reaction [4]. Perhaps most importantly, while Maertens and our group used a similar methodology, the use of 0.25 M NH4 SCN dissolved only the low and spared the high avidity http://dx.doi.org/10.1016/j.vaccine.2015.05.090 0264-410X/© 2015 Elsevier Ltd. All rights reserved.
antigen–antibody complexes thereby enhancing our ability to better discriminate between the women according to timing of Tdap administration. Accordingly, in order to obtain the optimal measurement of RAI over a wide range of IgG concentrations, it is of importance to utilize the lowest possible chaotropic agent concentration [5], that will dissolve only the low avidity antigen–antibody complexes to minimize the indiscriminate breaking of all (low and high) antigen–antibody avidity complexes. We hope that future studies from various countries will provide data on the RAI of IgG to PT that will enhance our understanding of the multiple factors, e.g., epidemiology, vaccine coverage, vaccine formulation and timing of Tdap administration to the pregnant involved in antibody avidity. Conflict of interest The authors do not have an association that might pose a conflict of interest. References [1] Abu Raya B, Bamberger E, Almog M, Peri R, Srugo I, Kessel A. Immunization of pregnant women against pertussis: the effect of timing on antibody avidity. Vaccine 2015;(March), http://dx.doi.org/10.1016/j.vaccine.2015.02.059, pii: S0264-410X(15)00248-0. [2] Almanzar G, Ottensmeier B, Liese J, Prelog M. Assessment of IgG avidity against pertussis toxin and filamentous hemagglutinin via an adapted enzyme-linked immunosorbent assay (ELISA) using ammonium thiocyanate. J Immunol Methods 2013;387(1–2):36–42. [3] Leuridan E, Hoang TTH, Maertens K, Nguyen DT, Duong TH, Caboré RN, et al. Pertussis antibody responses in maternal and cord blood samples after vaccination during pregnancy: a Belgian–Vietnamese collaboration. In: Poster 364 Presented at ESPID 2014. 2014. [4] Reverberi R, Reverberi L. Factors affecting the antigen–antibody reaction. Blood Transfus 2007;5(4):227–40. [5] Romero-Steiner S, Holder PF, Gomez de Leon P, Spear W, Hennessy TW, Carlone GM. Avidity determinations for Haemophilus influenzae Type b anti-polyribosylribitol phosphate antibodies. Clin Diagn Lab Immunol 2005;12(9):1029–35.
Bahaa Abu Raya a,b,∗ Department of Pediatrics, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel b The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St. 1, Haifa 31096, Israel
a
Isaac Srugo a,b,c Department of Pediatrics, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel b The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St. 1, Haifa 31096, Israel c Clinical Microbiology Laboratory, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel a
Reply to Letter to the Editor / Vaccine 33 (2015) 5490–5491
Ellen Bamberger a,b The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St. 1, Haifa 31096, Israel b Clinical Microbiology Laboratory, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel a
a
Aharon Kessel a,b The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Efron St. 1, Haifa 31096, Israel b Division of Allergy and Clinical Immunology, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel
5491
∗ Corresponding author at: Department of Pediatrics, Bnai Zion Medical Center, Golomb St. 47, Haifa 31048, Israel. Tel.: +972 52185125. E-mail address: baha [email protected] (B. Abu Raya)
5 April 2015 Available online 9 June 2015
