The Effect of Maternal Pertussis Immunization on Infant Vaccine Responses to a Booster Pertussis-Containing Vaccine in Vietnam
The Effect of Maternal Pertussis Immunization on Infant Vaccine Responses to a Booster Pertussis-Containing Vaccine in Vietnam
Kirsten Maertens 0
Thi Thu Ha Hoang 1
Trung Dac Nguyen 1
Ra?ssa Nad?ge Cabor? 2
Thi Hong Duong 1
Kris Huygen 2
Niel Hens 3 4
Pierre Van Damme 0
Duc Anh Dang 1
Elke Leuridan 0
0 Centre for the Evaluation of Vaccination, Vaccine and Infectious Diseases Institute, University of Antwerp , Belgium
1 Bacteriology Department, National Institute of Hygiene and Epidemiology , Hanoi , Vietnam
2 National Reference Centre Bordetella, National Reference Centre Toxigenic Corynebacteria, Service Immunology, Scientific Institute of Public Health , Brussels
3 Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University
4 Centre for Health Economics Research and Modeling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp , Belgium
Background. Maternal vaccination with an acellular pertussis (aP)-containing vaccine is a recommended strategy in a growing number of industrialized countries, to protect young infants from disease. Little is known on the effect of this strategy in low- and middle-income countries. Following a previous report on the effect of adding a pertussis and diphtheria component to the tetanus vaccination program in pregnant women in Vietnam, we report on infant immune responses to a booster aP vaccine dose in this randomized controlled clinical trial. Methods. Thirty infants of Tdap (tetanus, diphtheria, and acellular pertussis)-vaccinated pregnant women and 37 infants of women vaccinated with a tetanus-only vaccine received a fourth aP-containing vaccine dose in the second year of life. Blood was taken 1 month after the fourth infant dose. Immunoglobulin G (IgG) antibodies against pertussis toxin (PT), filamentous hemagglutinin (FHA), pertactin (Prn), tetanus toxoid (TT), and diphtheria toxoid (DT) were measured using commercially available enzyme-linked immunosorbent assays (ELISA). Results. One month after the booster dose, significantly lower antibody titers were measured in the Tdap group for anti-TT IgG (P < .001) only. Anti-DT IgG, anti-PT IgG, anti-Prn IgG, and anti-FHA IgG antibody titers were comparable for both groups. A rise in antibody concentrations was elicited for all (except DT) antigens after boosting. Conclusions. The present results indicate that the blunting of infant pertussis responses induced by maternal immunization, measured after a primary series of aP vaccines, was resolved with the booster aP vaccine dose. These results add to the evidence for national and international decision makers on maternal immunization as a vaccination strategy for protection of young infants against infectious diseases.
In 2014, global coverage of the 3 primary infant DTP
(diphtheria, tetanus, pertussis) vaccine doses was as high as 86%. Despite
these successful global pertussis vaccination programs, the
disease remains an important public health issue, causing an
estimated 63 000 deaths in children <5 years of age (2013) [
Mainly young infants, too young to be protected by the
currently available vaccines and vaccination schedules, are prone to
severe pertussis disease and have the highest hospitalization and
complication rates among the population [
Vaccination during pregnancy has been implemented in
national vaccination programs to elicit high titers of maternal
antibodies, as a means to protect young infants from disease
]. High titers of maternal antibodies induced by maternal
vaccination have already been shown to interfere with the infant
humoral immune response on primary acellular pertussis (aP)
]. This blunting effect ceased after a fourth aP
vaccine dose at the age of 12 months in a randomized controlled
trial conducted in the United States . Yet, few data are
available on infant immune responses to a fourth pertussis vaccine
dose using different intervals in infant immunization schedules.
In Vietnam, infant pertussis vaccination with whole-cell
pertussis (wP) vaccines started in 1985. Prior to that, the incidence
of pertussis was up to 84.4 per 100 000 (1984) [
]. Overall, the
reported incidence is now relatively low. In 2015, based on
clinical criteria, 309 pertussis cases were reported, resulting in an
incidence of 0.3 per 100 000 ( personal communication,
National Institute of Hygiene and Epidemiology [NIHE], Vietnam). In
the period 2011?2013, >50% of the cases occurred in infants <1
year of age. In 2014, 92 of 102 pertussis cases were reported in
infants aged <6 months [
Maternal Pertussis Vaccination in Vietnam
The World Health Organization (WHO) recommends the
use of wP vaccines within the Expanded Programme on
Immunization (EPI) [
] whenever a 3 + 1 infant-only schedule is used.
National programs currently administering wP vaccination
should continue to use wP vaccines for the primary vaccination
schedule. A switch from wP to aP vaccines for primary infant
immunization should only be considered when additional
boosters or maternal immunization are included in the national
immunization schedule [
We have previously reported on the effect of high titers of
maternal antibodies on the primary infant immune responses
to aP infant vaccines in Vietnam, after maternal vaccination
during pregnancy with a combined tetanus, diphtheria, and
aP (Tdap) vaccine (Adacel, Sanofi Pasteur, Canada) [
present article assesses the possible remaining blunting effect
of maternal immunization with the infant humoral immune
responses after a fourth aP-containing vaccine dose, administered
in the second year of life.
MATERIALS AND METHODS
A randomized controlled study was conducted in accordance
with the Helsinki Declaration, Good Clinical Practice, and the
procedures established by Vietnamese law. Ethical approval was
obtained (NIHE, Vietnam: No. 05IRB-120412; No.
IRBVN1059-02; and Ministry of Health: No.
978/CN-BYT131112). Written informed consent was signed by all
participants and both parents of the infants. Extended information
on material and methods has been reported previously [
Participating children were included in either a Tdap group?
that is, children born from women vaccinated with an
aP-containing vaccine (Adacel) between 18 and 36 weeks of
pregnancy?or a tetanus toxoid (TT) group?that is, children
born from women vaccinated with a tetanus-only vaccine
(TTInstitute of Vaccine and Biological Products [IVAC], Hanoi,
Vietnam) during pregnancy, as recommended within the EPI.
Within the present study, all infants received Infanrix Hexa
(GSK Biologicals, Rixensart, Belgium) for primary vaccination
at the age of 2, 3, and 4 months [
]. A fourth Infanrix Hexa dose
was planned to be administered at the age of 18 months. Due to
delay in the approval of the ethics committee, resulting in a
suspension of approximately 4 months, some of the infants within
this study were already vaccinated with a wP-containing vaccine
(DTP) within the EPI, whereas most children received Infanrix
Hexa as a booster dose in the second year of life.
From all children in the study, data on health status and
growth parameters were collected at the moment of the fourth
Infants received either the hexavalent vaccine Infanrix Hexa
(GSK Biologicals, Belgium) or a DTwP (diphtheria, tetanus,
wP) vaccine (IVAC). Infanrix Hexa contains 10 limit of
flocculation units (Lf ) TT, 25 Lf diphtheria toxoid (DT), 25
?g pertussis toxin (PT), 25 ?g filamentous hemagglutinin
(FHA), and 8 ?g pertactin (Prn) plus inactivated poliovirus,
hepatitis B surface antigens, and Haemophilus influenzae type
B polysaccharide. The DTwP vaccine used in the study contains
purified diphtheria anatoxin (30 International Units [IU]),
purified tetanus anatoxin (60 IU), and inactivated wP (4 IU)
adsorbed by aluminum phosphate.
All infant vaccines were administered at the Commune Health
Center (CHC) during the second year of life [
]. Blood samples
were collected from the infants 1 month after the fourth vaccine
dose. All blood samples were collected at the CHC and
transported to the Ha Nam Preventive Medicine Center on the
same day. Samples were centrifuged and stored at ?80?C. All
samples were monthly sent to the Department of Bacteriology
All frozen samples were transported to the Scientific Institute of
Public Health in Brussels, Belgium, and tested with
commercially available enzyme-linked immunosorbent assay (ELISA)
kits. The Virion/Serion kit (ANL, Copenhagen) was used to
detect anti-PT immunoglobulin G (IgG) antibodies and the
Euroimmune ELISA kit was used to detect anti-FHA and anti-Prn
IgG antibodies. Anti-TT and anti-DT IgG antibodies were
detected using the Virotech/Sekisui ELISA kit. Serum samples
were tested at a dilution of 1:100. ELISA results were expressed
in international units per milliliter (IU/mL), using respective
WHO standards (National Institute for Biological Standards
and Control [NIBSC] code 06/140 for pertussis, NIBSC code
TE-3 for tetanus, and NIBSC code 00/496 for diphtheria). For
pertussis, these international units are equivalent to the ELISA
units of the Center for Biologics Evaluation and Research, US
Food and Drug Administration [
]. The lower limit of
detection of the assays was 0.7 IU/mL for PT, 1 IU/mL for FHA, 3
IU/mL for Prn, 0.01 IU/mL for TT, and 0.03 IU/mL for DT.
To guarantee the reliability of the results, an international
independent validation was performed at the Canadian Center for
Vaccinology in Halifax, Canada [
4, 5, 11
For pertussis, a protective threshold of antibodies (correlate
of protection) is not known [
]. However, low antibody
concentrations are correlated with susceptibility to pertussis
]. For tetanus and diphtheria, the correlate of
protection is defined as 0.1 IU/mL for tetanus and 0.01?0.1
IU/mL for diphtheria.
In this paper, blunting of the immune response after the
fourth vaccine dose among infants was defined by the authors,
similarly to a previous publication [
], as a significantly lower
geometric mean concentration (GMC) of specific IgG
antibodies, measured 1 month after the fourth vaccine dose in the Tdap
group compared to the TT (control) group.
The initial sample size calculation was based on previous results
]; a population of 50 subjects in each study arm would be
sufficient to detect significant differences in antibody titers of
IgG in cord and newborns. No additional sample size
calculation has been performed, due to a lack of data for the
postbooster time point at the conception of the study. The original aim
was to vaccinate all infants with an aP-containing vaccine for
their fourth vaccine dose. Due to unforeseen circumstances,
some children were vaccinated with a wP-containing vaccine,
resulting in a smaller number of aP-vaccinated infants in
both study groups, mainly in the Tdap group. Therefore, the
study might be underpowered because of these unforeseen
Disease-specific antibody GMCs and 95% confidence intervals
(CIs) were calculated at each time point in both study groups.
Descriptive analyses were performed to identify possible
differences between both study groups. Statistical tests included
parametric tests: ( paired) t tests and ?2 tests and their nonparametric
alternatives: ( paired) Wilcoxon tests and Fisher exact tests
whenever the underlying assumptions of the parametric tests were
violated (ie, normality and sparseness assumptions, respectively)
]. Linear regression models were used to identify
characteristics that could potentially impact infant antibody titers 1
month after the administration of a fourth vaccine dose.
The analysis was performed using SPSS statistical software
version 23.0. A 2-sided P value <.05 was considered statistical
General Characteristics of the Study Population
Characteristics of the mother?infant pairs until 5 months after
delivery as well as exclusion criteria at baseline have been
described in a previous publication [
]. Children were born
between 22 February 2013 and 7 October 2013. After birth, 51
children were included in the Tdap group and 48 children in
the TT group. After the primary series of 3 aP-containing
vaccines, 15 children from the Tdap group and 4 children from the
TT group were vaccinated ?not according to protocol? with a
wP vaccine as a fourth vaccine dose. Due to loss to follow-up,
6 additional children from the Tdap group and 7 additional
children from the TT group were excluded from the study. In
the end, 30 infants were included in the Tdap group and 37
infants in the TT group for analysis of the postbooster responses.
Infants were vaccinated with a fourth aP-containing vaccine
(Infanrix Hexa) between 4 April 2015 and 10 May 2015 at a
mean age of 22.18 months (range, 18.5?24.7 months). All
children were in good health at the moment of vaccination. Blood
samples were taken on average 30.2 days (range, 30?33 days)
after the fourth vaccine dose between 7 May 2015 and 10
Comparing demographics between children from the Tdap
group and children from the TT group, a significantly smaller
interval between vaccine dose 3 and vaccine dose 4 was found in
the TT group (P = .010; Table 1).
The clinical history of the participants did not identify any
pertussis disease case in the infants nor in the households
during the entire study period.
Table 2 provides an overview of the GMCs of IgG antibodies to
TT, DT, and 3 pertussis-specific antigens in the sera of all
infants at delivery, before the start of the primary pertussis
vaccination, 1 month after the primary pertussis vaccination and 1
month after the administration of the fourth aP-containing
vaccine dose during the second year of life.
One month after a primary series of 3 doses of the hexavalent
aP vaccine, significantly lower antibody titers were observed in
infants from the Tdap group compared with infants from the
TT group for anti-Prn IgG (GMC, 83 [95% CI, 65?104] vs
132 [95% CI, 104?168]; P = .006) and anti-DT IgG (GMC,
1.96 [95% CI, 1.62?2.30] vs 2.80 [95% CI, 2.48?3.12];
P < .001) antibodies. For anti-TT IgG, anti-PT IgG, and
antiFHA IgG, however, comparable but higher antibody titers
were reported in infants from the Tdap group compared with
infants from the TT group [
One month after the administration of the fourth
aPcontaining vaccine, GMCs to anti-TT IgG (GMC, 2.7 [95%
CI, 2.4?3.1] vs 4.2 [95% CI, 3.7?4.7]; P < .001) were significantly
lower in infants from the Tdap group compared with infants
from the TT group. For anti-DT IgG, anti-PT IgG, anti-FHA
IgG, and anti-Prn IgG, comparable but lower antibody titers
were found in infants from the Tdap group compared to infants
from the TT group.
CID 2016:63 (Suppl 4)
after a booster vaccination with an aP-containing vaccine
during the second year of life. Previously, blunting of the infant
immune response by maternal vaccination during pregnancy, in
comparison with a control group receiving a tetanus-only
vaccine during pregnancy, has been described for anti-DT and
anti-Prn antibodies after a primary series of 3 aP-containing
infant vaccines [
The present data indicate that a blunting effect by maternal
immunization only persists on the anti-TT IgG titers in the
Tdap group, 1 month after a fourth vaccine dose is offered
in the second year of life, compared to the TT group. For
anti-PT IgG, anti-FHA IgG, anti-Prn IgG, and anti-DT IgG,
comparable but lower titers are measured in the Tdap group
compared with the TT group. Nevertheless, a good humoral
immune response is reported in both study groups, with a
significant rise of antibody titers for all measured antigens, except
DT-oriented antibodies, upon the fourth vaccine dose. The
interval between vaccine dose 3 and 4 was significantly smaller
in the TT group (16.58 months [SEM, 0.26 months] vs 17.44
months in the Tdap group [SEM, 0.17 months]; P = .01). But
this was only affecting the anti-FHA antibody titers in the
CID 2016:63 (Suppl 4)
In comparison with the available literature on general infant
humoral immune responses to a booster dose of Infanrix Hexa
in the second year of life [
], some slight differences were
found. Tichmann et al  collected blood samples after a
fourth dose of Infanrix Hexa administered at 12?19 months
of age. And Gimenez-Sanchez et al [
] collected blood samples
after a fourth dose of Infanrix Hexa at 11?15 months of age,
administered concomitantly with 7- or 13-valent pneumococcal
conjugate vaccine. Different laboratory tests were used in both
studies compared to this study. Antibody titers to anti-PT IgG,
measured at 1 month after the fourth vaccine dose, are
] or higher [
] in the present study in both groups and
antibody titers of anti-FHA IgG, anti-Prn IgG, and anti-DT IgG
are lower in our study compared with both other publications
]. On the other hand, we report lower anti-TT antibody
titers after the booster dose compared with the Tichmann et al
study , but higher compared with the Gimenez-Sanchez
et al study [
The clinical relevance of the lower antibody titers in children
from vaccinated mothers after a fourth vaccine dose, yet rising
titers compared to the post?primary time point within one
study group, is a point of discussion, as no correlate of
protection is known for pertussis. But high concentrations of anti-PT
IgG and anti-Prn IgG are associated with protection against
pertussis disease and mainly anti-PT antibodies are considered
to be crucial for this protection [
]. No clinical cases of
pertussis were identified within our study population. However, in
Vietnam, pertussis disease is only diagnosed based on a clinical
definition. Laboratory diagnosis is not obtained because
diagnostic equipment is not available at the community level.
Therefore, underdiagnosis is highly probable. Antibody titers
for tetanus and diphtheria remained above the correlate of
protection both after primary and booster vaccination.
In the study performed by Mu?oz et al [
], blunting of the
antibody response after primary vaccination (at 2, 4, and 6
months) was also reported. This effect disappeared with the
administration of a fourth vaccine dose at 12 months of age.
Similarly, Hardy-Fairbanks et al [
] reported a slight blunting of
the immune response after primary vaccination. Yet, after
administration of a fourth vaccine dose at 12?18 months of age,
no notable differences in antibody concentrations were
encountered anymore between infant groups. In a Belgian study, a similar
blunting effect on the immune response after primary vaccination
(2, 3, and 4 months) was described [
]. After the administration of
a fourth vaccine dose at 15 months of age, only a significant
blunting effect remained for the anti-PT antibodies [
The differences observed between the present data and the
studies described above [
3, 5, 11, 21
] could be due to the use
of other vaccine brands in pregnant women or during infancy,
to distinct primary vaccination schedules, to another timing of
the administration of the fourth vaccine dose, different
laboratory tests used [
], or possible confounders between
populations (eg, different demographic composition of the study
population, different disease-specific epidemiological
background, different vaccination history).
The blunting effect described is in contradiction with the
observations in mice by Feunou et al where less blunting effect is
described whenever different brands of vaccines are used in
mothers and infants [
] compared with the same brand in
mother and offspring. However, taking into consideration the
small sample size of our study, the possible effect of the use
of vaccines from several manufacturers certainly needs to be
further investigated in future studies.
The linear regression model identified no persistent
influencing factor on the antibody titers measured at 1 month after the
fourth vaccine dose in our study population. Only single
significant influences of some variables on 1 specific antigen at 1
specific time point were found (eg, sex on anti-DT IgG and
interval between vaccine dose 3 and 4 on anti-FHA IgG).
The original design of this study was to vaccinate all
participating infants with the wP vaccine used within the EPI. Due to
previously described fatalities among young infants in Vietnam,
and subsequent disruption of the national program, Infanrix
Hexa was approved to be administered to all participating
]. Then again, due to an unforeseen delay in the ethical
approval of the booster dose administration within the study, 19
children overall (Tdap and TT group) received a fourth
(booster) wP vaccine dose within the regular Vietnamese EPI
services. This situation created the unique opportunity to report on
different infant vaccination schedules after maternal
immunization. Within the Tdap group, all measured antibody titers in
wP-boosted infants were lower compared with the antibody
titers in aP-boosted infants. For anti-PT IgG, these antibody
titers were even significantly lower. These lower antibody titers
could potentially be influenced by the longer interval between
the fourth vaccine dose and blood sampling in the wP-boosted
infants (see Supplementary Table 1 for details). Yet the
difference in the anti-PT antibody titers is unlikely to be solely the
consequence of the longer time lapse between booster vaccine
and blood sampling. It is well known that higher antibody
responses to aP vaccination are elicited compared with wP
vaccination in infants after both primary and booster vaccination
Limitations of the Study
Our study has a number of limitations. First, no blood samples
were taken before the administration of the fourth vaccine dose.
Consequently, we could not describe the antibody decay
between the third and fourth vaccine dose.
Second, due to a delay in ethical approval, not all children
were vaccinated with the same vaccine as a fourth vaccine
dose. Some children were already vaccinated within the
standard EPI healthcare system before ethical approval was
obtained. However, these unforeseen circumstances offered the
opportunity to investigate different schedules of boosting.
During the follow-up of the study, we experienced a
dropout rate due to moving of participants to other provinces.
The lower sample size of the study resulted in larger confidence
intervals and lower statistical power, but we were still able to
detect significant differences 1 month after the fourth vaccine
Pertussis vaccination during pregnancy closes adequately the
susceptibility gap for infection in young unvaccinated infants.
Previously, blunting of the infant immune response after 3
doses of an aP-containing vaccine has been reported for the
anti-DT and anti-Prn antibody immune response in infants
in Vietnam, when vaccination is performed in the presence of
high titers of maternal antibodies after a 3-dose priming
schedule. After the fourth dose with a pertussis-containing vaccine in
the second year of life, significant blunting is reported for the
anti-TT antibody immune responses. However, a strong
humoral immune response on the fourth vaccine dose is elicited
for all antigens, except DT, in both groups of infants from either
Tdap- or TT-vaccinated women.
The data reported in this manuscript can add evidence for
national and international decision makers on maternal
immunization as a vaccination strategy for protection of young
infants against infectious diseases. Further research on
pertussis vaccination during pregnancy in low- and middle-income
countries is certainly needed to assess the impact of high
maternal antibody levels on the immune response of infants both
primed with aP- or wP-containing vaccines. An additional
comparative study on different brands of pertussis vaccines
could shed further light on the induction of qualitative and
quantitative differences between the induced immune
Supplementary materials are available at http://cid.oxfordjournals.org.
Consisting of data provided by the author to benefit the reader, the posted
materials are not copyedited and are the sole responsibility of the author, so
questions or comments should be addressed to the author.
Acknowledgments. The authors would like to thank all participating
children; all collaborators in the health centers for assistance in recruitment
and performing blood sampling; and Nguyen Thuy Tram, MSc, Pham
Thanh Hai, MSc, and Luong Minh Hoa, MSc, at the Department of
Bacteriology, National Institute of Hygiene and Epidemiology, Hanoi, Vietnam, for
their assistance and dedication.
Author contributions. E. L. and P. V. D. wrote the protocol of the study;
E. L., K. M., and P. V. D. were the coordinators of the study; H. T. T. H.,
N. T. D., D. T. H., and D. D. A. performed the clinical study in Vietnam;
R. N. C. and K. H. performed the laboratory analyses; N. H. and
K. M. performed the statistics.
Financial support. This work was supported by VLIR-UOS (Flemish
Interuniversity Council) (ZEIN2012Z131) and Fund for Scientific
Research?Flanders (FWO) (G.A032.12N) together with the National
Foundation for Science and Technology Development?NAFOSTED
(FWO.2011.03) and the Antwerp Study Centre for Infectious Diseases
(ASCID). E. L. is beneficiary of a postdoctoral mandate fellowship from
the FWO (FWO 12D6114N). N. H. gratefully acknowledges support from
the University of Antwerp scientific chair in Evidence-Based Vaccinology,
financed in 2009?2016 by a gift of Pfizer. R. N. C. was partially funded by
BELSPO (Federal Service Science Policy). Part of this work was performed
in the frame of the Belgian National Reference Centre for Bordetella
pertussis, supported by the Belgian Ministry of Social Affairs through a fund
within the Health Insurance System.
Supplement sponsorship. This article appears as part of the supplement
?Infant Pertussis Disease Burden in the Context of Maternal Immunization
Strategies,? sponsored by the Bill & Melinda Gates Foundation.
Potential conflicts of interest. N. H. receives support from the
University of Antwerp scientific chair in Evidence-Based Vaccinology, financed in
2009?2016 by a gift of Pfizer. All other authors report no potential conflicts.
All authors have submitted the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the editors consider relevant to the
content of the manuscript have been disclosed.
Maternal Pertussis Vaccination in Vietnam
1. World Health Organization. Pertussis vaccines: WHO position paper-August 2015 , Available at: http://www.who.int/wer/2015/wer9035.pdf? ua=1. Accessed 3 August 2016 .
2. Berti E , Chiappini E , Orlandini E , Galli L , de Martino M. Pertussis is still common in a highly vaccinated infant population . Acta Paediatr 2014 ; 103 : 846 - 9 .
3. Munoz FM , Bond NH , Maccato M , et al. Safety and immunogenicity of tetanus diphtheria and acellular pertussis (Tdap) immunization during pregnancy in mothers and infants: a randomized clinical trial . JAMA 2014 ; 311 : 1760 - 9 .
4. Hoang HT , Leuridan E , Maertens K , et al. Pertussis vaccination during pregnancy in Vietnam: results of a randomized controlled trial . Vaccine 2016 ; 34 : 151 - 9 .
5. Maertens K , Cabore RN , Huygen K , Hens N , Van Damme P , Leuridan E. Pertussis vaccination during pregnancy in Belgium: results of a prospective controlled cohort study . Vaccine 2016 ; 34 : 142 - 50 .
6. Ladhani SN , Andrews NJ , Southern J , et al. Antibody responses after primary immunization in infants born to women receiving a pertussis-containing vaccine during pregnancy: single arm observational study with a historical comparator . Clin Infect Dis 2015 ; 61 : 1637 - 44 .
7. Ministry of Health. Vietnam EPI report of the Ministry of Health: 25 years of the Expanded Program on Immunization . 2012 . Available at: http://www. tiemchungmorong. vn/vi. Accessed 24 August 2016 .
8. Hoang Thi Thu H , Nguyen TT , Pham TH , et al. Direct PCR for detection of Bordetella pertussis from clinical specimens in Vietnam . J Prev Med 2014 ; 11 : 8 - 13 .
9. World Health Organization. Revised guidance on the choice of pertussis vaccines: July 2014 . WER 2014 , 89 , 337 - 344 . Geneva, Switzerland: WHO, 2014 .
10. van der Zee A , Schellekens JF , Mooi FR . Laboratory diagnosis of pertussis. Clin Microbiol Rev 2015 ; 28 : 1005 - 26 .
11. Maertens K , Cabore RN , Huygen K , et al. Pertussis vaccination during pregnancy in Belgium: follow-up of infants until 1 month after the fourth infant pertussis vaccination at 15 months of age . Vaccine 2016 ; 34 : 3613 - 9 .
12. Plotkin SA . Correlates of protection induced by vaccination . Clin Vaccine Immunol 2010 ; 17 : 1055 - 65 .
13. Storsaeter J , Hallander HO , Gustafsson L , Olin P . Low levels of antipertussis antibodies plus lack of history of pertussis correlate with susceptibility after household exposure to Bordetella pertussis . Vaccine 2003 ; 21 : 3542 - 9 .
14. Cherry JD , Gornbein J , Heininger U , Stehr K. A search for serologic correlates of immunity to Bordetella pertussis cough illnesses . Vaccine 1998 ; 16 : 1901 - 6 .
15. Leuridan E , Hens N , Peeters N , de Witte L , Van der Meeren O , Van Damme P. Effect of a prepregnancy pertussis booster dose on maternal antibody titers in young infants . Pediatr Infect Dis J 2011 ; 30 : 608 - 10 .
16. Neter J , Kutner M , Nachtsheim C , Wasserman W. Applied linear statistical models. 4th ed. Chicago: Irwin, 1996 .
17. Agresti A . Categorical data analysis . 2nd ed. New York: Wiley, 2002 .
18. Tichmann I , Grunert D , Habash S , et al. Persistence of antibodies in children primed with two different hexavalent diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus and Haemophilus influenzae type B vaccines and evaluation of booster vaccination . Hum Vaccin 2006 ; 2 : 249 - 54 .
19. Gimenez-Sanchez F , Kieninger DM , Kueper K , et al. Immunogenicity of a combination vaccine containing diphtheria toxoid, tetanus toxoid, three-component acellular pertussis, hepatitis B, inactivated polio virus, and Haemophilus influenzae type b when given concomitantly with 13-valent pneumococcal conjugate vaccine . Vaccine 2011 ; 29 : 6042 - 8 .
20. Heininger U , Riffelmann M , Bar G , Rudin C , von Konig CH . The protective role of maternally derived antibodies against Bordetella pertussis in young infants . Pediatr Infect Dis J 2013 ; 32 : 695 - 8 .
21. Hardy-Fairbanks AJ , Pan SJ , Decker MD , et al. Immune responses in infants whose mothers received Tdap vaccine during pregnancy . Pediatr Infect Dis J 2013 ; 32 : 1257 - 60 .
22. Feunou PF , Mielcarek N , Locht C . Reciprocal interference of maternal and infant immunization in protection against pertussis . Vaccine 2016 ; 34 : 1062 - 9 .
23. Dirix V , Verscheure V , Goetghebuer T , et al. Cytokine and antibody profiles in 1- year-old children vaccinated with either acellular or whole-cell pertussis vaccine during infancy . Vaccine 2009 ; 27 : 6042 - 7 .
24. Guiso N , Njamkepo E , Vie le Sage F , et al. Long-term humoral and cell-mediated immunity after acellular pertussis vaccination compares favourably with wholecell vaccines 6 years after booster vaccination in the second year of life . Vaccine 2007 ; 25 : 1390 - 7 .