Neonatal Vaccination with an Acellular Pertussis Vaccine Accelerates the

Acquisition of Pertussis Antibodies in Infants

MARKUS KNUF, MD, HEINZ-JOESF SCHMITT, MD, JOANNE WOLTER, MBBS, LODE SCHUERMAN, MD, JEANNE-MARIE JACQUET, PHD,
DOROTHEE KIENINGER, MD, CLAIRE-ANNE SIEGRIST, MD, AND FRED ZEPP, MD

Objectives

Because young infants are at highest risk of pertussis complications, this study assessed whether neonatal
acellular pertussis (aP) vaccination could provide earlier immunity.
Study design Neonates (n 121) were randomly assigned (1:1) to receive either aP or hepatitis B vaccine (HBV) (controls)
vaccine at birth, followed by vaccination with DTaP-HBV-IPV/Hib at 2, 4 and 6 months. Immune responses were measured.
Reactogenicity was assessed for 7 days after each dose.
Results The aP birth dose was followed by few adverse events. Reactogenicity of subsequent vaccine doses did not differ
between groups. Seven serious adverse events were reported from each group; none were related to the study vaccines. At 3
months of age, vaccination with aP at birth had induced significantly higher antibody responses to the 3 pertussis antigens
compared with controls. At 7 months, geometric mean/concentrations of antibodies against pertussis antigens were similar in
both groups, and all subjects had reached seroprotective antibody concentrations against diphtheria, tetanus, and poliovirus
types 1, 2, and 3. Geometric mean/concentrations of antibodies to haemophilus influenzae type b (Hib) and HBV were
significantly lower in the aP group.
Conclusions Early neonatal immunization with aP was safe, well tolerated, and resulted in earlier antibody responses, seen
after the first dose of a DTaP combination vaccine. Birth dose of aP did not induce
immunologic tolerance to pertussis antigens but appear to dampen responses to Hib and
HBV vaccines. (J Pediatr 2008;152:655-60)

ertussis is most severe in young infants,1 yet vaccination against this disease begins
no earlier than 6 weeks of age and frequently as late as 3 months of age, depending
on the local vaccination schedule. The window of susceptibility to pertussis
infection frequently is prolonged further due to suboptimal compliance with recommended vaccination schedules.2 Various potential strategies have been reviewed or recommended in countries with the aim of better protecting infants against pertussis. These
include selective vaccination of close contacts of neonates, universal adult immunization,
adolescent or preschool pertussis boosters, and maternal immunization.3 The feasibility of
a birth dose of combined diphtheria-tetanus-whole cell pertussis (DTwP) vaccine to
provide early protection against pertussis had been investigated 40 years ago. Vaccination
of newborn infants with DTwP resulted in so-called immune tolerance, whereby
primary and booster antibody responses to the antigens of Bordetella pertussis were
persistently reduced compared with infants who began their vaccination course later in
life.4,5 As a result, the strategy of immunizing newborn infants against pertussis was
abandoned.
In an animal model, immunization of neonatal (7-day-old) mice with DTwP
induced lower antibody responses than those observed after vaccination of older infant
mice,6 thus supporting the early human data. Immunization of neonatal mice with DT

aP
DTa(w)P

Acellular pertussis vaccine

Combined diphtheria-tetanus-acellular
(whole cell) pertussis vaccine
GMT/GMC Geometric mean titer/concentration
HBsAg
Hepatitis B surface antigen
HBV
Hepatitis B vaccine

Hib
PT
FHA
PRP
PRN

Haemophilus influenzae type b

Pertussis toxoid
Filamentous hemagglutinin
Polyribosyl-ribitol-phosphate
Pertactin

From the Paediatric Immunology and Infectious Diseases (M.K., H.S., D.K., F.Z.),
Childrens Hospital, Johannes Gutenberg
University of Mainz, Mainz, Germany;
GlaxoSmithKline Biologicals (J.W., L.S., J.J.),
Rixensart, Belgium; and the Center for Vaccinology and Neonatal Immunology (C.S.),
University of Geneva, Switzerland.
Supported by GlaxoSmithKline Biologicals,
Rixensart, Belgium (study number 210602/
002). Drs Wolter, Jacquet, and Schuerman
are/were employees of GSK Biologicals at
the time the study was performed. Dr
Claire-Anne Siegrist, Professor Schmitt,
Professor Zepp, and Dr Knuf have received
honoraria for participation to scientific advisory boards of GSK/other pharmaceutical
companies as well as research grants from
pharmaceutical companies within the past
3 years. Dr Kieninger declares no potential
conflict of interest.
Submitted for publication Feb 2, 2007; last
revision received Aug 22, 2007; accepted
Sep 19, 2007.
Reprint requests: Dr Markus Knuf, Department of Paediatric Immunology and
Infectious Diseases, Zentrum Prventive
Pdiatrie der Johannes Gutenberg-Universitt, Langenbeckstrae 1, D-55131
Mainz, Germany. E-mail: knuf@kinder.klinik.
uni-mainz.de.
0022-3476/$ - see front matter
Copyright 2008 Mosby Inc. All rights
reserved.
10.1016/j.jpeds.2007.09.034

655

acellular pertussis (aP) vaccine, however, elicited highly immunogenic and a similar anti-pertussis toxoid (PT) antibody
avidity as observed in infant mice.6 Encouraging preliminary
data in humans followed.7
We assessed the feasibility of giving a birth dose of a
3-component aP vaccine with regard to acceleration of the
immune responses against pertussis antigens. Since diphtheria
and tetanus are infrequently encountered in very young infants in industrialized countries, and because diphtheria and
tetanus toxoids frequently are used as protein carriers in
conjugate vaccines throughout childhood, we selected a
stand-alone aP vaccine to avoid unnecessary additional exposure to diphtheria and tetanus toxoids.

METHODS
Design
This exploratory phase II, double-blinded, controlled
study (210602/002) was conducted in Germany between July
14, 2004, and 3 April 3, 2006, according to the Declaration of
Helsinki, Good Clinical Practice guidelines, and applicable
German laws (Arzneimittelgesetz; AMG) with the approval
of relevant ethics review committees. Written informed consent was obtained from parents/guardians before enrolment of
vaccinees. Neonates were randomized to receive one dose of
either aP vaccine or hepatitis B vaccine (HBV) at age 2 to 5
days. Subsequently, all subjects received vaccination with
DTaP-HBV-IPV/Hib at 2, 4, and 6 months of age. Thus,
subjects in the control group received 5 doses of hepatitis B
vaccine compared with 4 doses in the aP group.
Subjects
Study subjects were healthy, 36- to 42-week-gestation
neonates 2 to 5 days of age, born after an uncomplicated
pregnancy to mothers seronegative for hepatitis B surface
antigen (HBsAg), with a birth weight 2.5 kg and a 5-minute
APGAR 7.
Subjects were excluded from participation if their
mother was known or suspected to be HIV-positive; if infants
had a major congenital defect, serious illness, or surgical
condition; if administration of immunosuppressants or other
immune-modifying drugs was planned during the study; if
there had been administration of immunoglobulins and/or
any blood products to the mother during pregnancy or to the
subject since birth or were planned during the study; if there
was a family history of congenital or hereditary immunodeficiency; if newborn infants were eligible for vaccination with
pneumococcal vaccine; or if BCG was planned during the
study period. The study was conducted in Germany between
July 2004 and April 2006. At the time of the study, routine
infant immunization with the pneumococcal vaccine was not
generally recommended.
Vaccines
All vaccines were manufactured by GlaxoSmithKline
(GSK) Biologicals, Rixensart, Belgium. A single dose of aP
656

Knuf et al

investigational vaccine (0.5 mL) contained 25 g PT, 25 g

filamentous hemagglutinin (FHA), 8 g pertactin (PRN),
and 0.5 mg aluminium as hydroxide salts. The adjuvant and
the antigen components of the aP vaccine were identical to
the pertussis component of the combined DTaP-HBV-IPV/
Hib vaccine (Infanrix hexa). The HBV vaccine (Engerix; B.
Kinder) contained 10 g recombinant HBsAg adsorbed on
0.25 mg aluminium as hydroxide salts. In addition to pertussis
antigens as above, each dose (0.5 mL) of DTaP-HBV-IPV/
Hib vaccine contained 30 IU diphtheria toxoid, 40 IU
tetanus toxoid, 10 g recombinant HBsAg, 40D, 8D, and
32D antigen units of poliovirus types 1, 2, and 3, respectively,
10 g Hib polyribosyl-ribitol-phosphate (PRP) conjugated to
tetanus toxoid, and 0.82 mg aluminium as hydroxide and
phosphate salts. All vaccines were administered intramuscularly into the left anterolateral thigh. Infanrix hexa and Engerix B are licensed in the European Union and other countries. Infanrix hexa is not licensed in the United States.

Assessment of Immunogenicity
A total of 4 blood samples were collected, the first just
before the first vaccine dose at age 2 to 5 days, and 1 each at
3, 5, and 7 months of age (corresponding to 1 month after
each dose of DTaP-HBV-IPV/Hib vaccine). Samples were
stored at 20C until analysis at GSK Biologicals, Belgium.
Anti-PT, anti-FHA, and anti-PRN IgG antibody concentrations were measured, at each blood sampling time point
by enzyme-linked immunosorbent assay (ELISA; cutoff 5
EL.U/mL defining seropositivity), as per GSK Biologicals
standard assay developed for licensure of DTaP vaccines. As
no serologic correlate of protection have been defined for
anti-pertussis antibodies, serologic response was assessed via
the calculation of vaccine response, defined in the statistical
section. For all other antibodies, concentrations at or above
the assay cutoff were considered protective. One month after
the last vaccine dose, anti-diphtheria, anti-tetanus, and antiPRP antibody concentrations were measured by ELISA (cutoff 0.1 IU/mL, 0.1 IU/mL and 0.15 g/mL, respectively);
antibodies against hepatitis B surface antigen (HBs) were
measured by ELISA (AUSAB, Abbot Laboratories) according to the manufacturers instructions (cutoff 10 mIU/mL);
anti-polio types 1, 2, and 3 antibody titers were measured by
virus micro-neutralization assay. The lowest dilution tested
was 1:8.
Assessment of Reactogenicity
Reactogenicity was assessed using diary cards for 8 days
(days 0 to 7) after each vaccination. Local reactions (pain,
redness, and swelling at the site of injection), and general
adverse events (fever [rectal temperature 38C], irritability/
fussiness, drowsiness, and loss of appetite) were actively solicited. Investigators graded symptom intensity on a 3-point
scale where grade 3 was defined as 39.5C (fever); cries
when limb is moved/spontaneously painful (pain); a diameter
50 mm (swelling and redness); crying or irritability that
The Journal of Pediatrics May 2008

could not be comforted/prevented normal activity (irritability/

fussiness), prevented normal activity (drowsiness), not eating
at all (loss of appetite). Any large swelling at the injection site
(defined as swelling with a diameter 50 mm, noticeable
diffuse swelling, or noticeable increase of limb circumference)
was specifically assessed by the investigator. All other adverse
events (unsolicited) occurring within 30 days of each vaccination were recorded. Serious adverse events (SAE) were
recorded during the entire study period until 30 days after the
last vaccination.

Statistical Analysis
The immunogenicity analysis was performed on the
according to protocol (ATP) cohort. This comprised all subjects who had complied with the vaccination schedule defined
in the protocol and with assay results available.
For all antigens, seropositivity/seroprotection/vaccine
response rates with exact 95% confidence intervals (CIs) were
calculated. Antibody GMC or titers (GMT) with 95% CIs
were calculated by taking the anti-log of the mean of the log
concentration/titer transformations. Antibody concentrations/titers below the assay cutoff were given an arbitrary
value of half the cutoff for the purpose of GMC/GMT
calculation.
The primary objective of the study was to assess the
immunogenicity and safety of aP vaccine administered soon
after birth. The occurrence of immune hyporesponsiveness
was assessed by (1) examining the proportion of initially
seronegative subjects (concentration 5 EL.U/mL) who seroconverted for pertussis antibodies after the third dose of
DTaP-HBV-IPV/Hib, (2) by assessment of a modified vaccine response defined as (a) in subjects with an initial antibody
concentration 20 EL.U/mL at birth, a pertussis antibody
concentrations 5 EL.U/mL 1 month after the final vaccination, (b) in subjects with an initial anti-pertussis antibody
concentration 20 EL.U/mL at birth, an antibody concentrations equal to or greater than one-fourth of their initial
antibody concentration (corresponding to 2 half-lives of decay
for maternal antibody), 1 month after the final vaccination.
The feasibility of accelerating protection against pertussis by means of a birth dose of aP was assessed in terms of
anti-pertussis GMC 1 month after the first dose of DTaPHBV-IPV/Hib. For exploratory comparisons of rates between the groups, P values were calculated using the 2-sided
Fisher exact test: a P value .05 indicated a possible group
difference. Groups also were compared by computation of
95% CI for the group GMC ratio for each pertussis antigen
using an ANCOVA model on the logarithm10 transformation of the concentrations. The 95% CI for the group GMC/
GMT ratio for other vaccine antigens 1 month after the final
vaccine dose was also calculated based on an ANOVA model.
Possible differences between groups were indicated by 95%
CI on the GMC/GMT ratios excluding 1. Detected differences should be interpreted with caution considering that
there was no adjustment for multiplicity of end points.

With 50 evaluable subjects per group, there was at least

86% power to exclude a 2-fold decrease in GMC between
groups (aP versus HBV) after the final vaccine dose assuming
a GMC ratio of 1, and at least 86% power to show superiority
in GMCs after the first dose of DTaP-HBV-IPV/Hib assuming a GMC ratio (control over aP group) of 0.5 for the
three pertussis antibodies.
The safety and reactogenicity analysis was performed on
the total vaccinated cohort.

RESULTS
A total of 121 neonates were enrolled and vaccinated:
60 in the aP at birth group and 61 in the control group. A
total of 54 subjects in the aP group and 56 subjects in the
HBV group completed the study, and 11 subjects withdrew
form the study. Parents of eight subjects (4 in each group)
withdrew consent for participation, 4 after the birth dose, 3
after the second vaccine dose, and 1 after the third. None of
these consent withdrawals were due to an adverse event.
Three subjects were withdrawn due to migration from the
study area or were lost to follow-up. The analysis of safety was
based on the total vaccinated cohort. The ATP cohort comprised 55 subjects in the aP group and 57 subjects in the
control group. Elimination from the immunogenicity ATP
cohort was due to lack of serologic data. The mean age of the
subjects in the total cohort at the time of birth vaccination was
2.9 days (range 2 to 5 days,). Boys and girls were similarly
represented in both groups, and 96.7% of subjects were Caucasian.

Reactogenicity
The birth dose of aP was as well tolerated as the birth
dose of the licensed HBV vaccine, with no statistically significant differences between groups detected. Redness was the
most commonly occurring local reaction, and irritability and
drowsiness were the most commonly occurring solicited general adverse events (Figure 2A; available at www.jpeds.com).
Fever (38C by rectal measurement) was not reported by
any subject after vaccination at birth. Adverse events of grade
3 intensity occurred in fewer than 1.7% of subjects.
Over all doses, the percentages of subjects with adverse
events and the intensity of these were similar between groups
(Figure 2B; available at www.jpeds.com). Fever occurred after
34.5% and 37.3% of subjects in the aP and HBV groups,
respectively. One subject (in the HBV group) reported fever
39.5C. Medical advice due to fever was sought for two
subjects (3.4%) in the aP group and for 5 subjects (8.5%) in
the HBV group in the 8-day follow-up period after vaccination, either after the third or the fourth vaccine dose. When
all doses were considered, no statistically significant differences between groups in the incidences by subject of local or
general solicited adverse events were observed. No large swelling reactions were observed.
Unsolicited adverse events during the 30-day follow-up
period after each vaccine dose were recorded in 80% of
subjects in the aP group and 77% of subjects in the HBV

Neonatal Vaccination with an Acellular Pertussis Vaccine Accelerates the Acquisition of Pertussis Antibodies in Infants

657

Table I. Immune responses to pertussis antigens (ATP cohort for immunogenicity)

Response to PT
Group aP

Response to FHA

Group HBV

Group aP

Response to PRN

Group HBV

Group aP

Group HBV

Age

% >5
EL.U/mL

% >5
EL.U/mL

% >5
EL.U/mL

% >5
EL.U/mL

% >5
EL.U/mL

% >5
EL.U/mL

Birth
3 months
5 months
7 months

52
50
48
50

55.8
100*
100
100

50
49
47
48

52
46.9*
100
100

53
51
49
51

94.3
100
100
100

50
49
47
48

92
95.9
100
100

52
50
48
50

51.9
98
100
100

50
49
47
48

48
93.9
97.9
100

*Statistically significant difference between groups (P .05 with 2-sided Fisher exact test).

group. Of these, 2 cases in each group (3.3%) were considered

by investigators to be related to vaccination: pain (2 cases),
crying, and rash. There were 14 SAE during the study, seven
in each group. These were cyanosis associated with acute
respiratory infection (respiratory syncytial virus, enterovirus),
pneumonia, pharyngitis, gastroenteritis and nasopharyngitis,
anal abscess, failure to thrive, bronchiolitis in the aP group;
neonatal ophthalmia, perianal abscess and fistula, gastroenteritis (2 subjects), neonatal jaundice, pyloric stenosis, poor
weight gain in the HBV group. None was considered by the
investigator to be related to vaccination.

Immunogenicity
PERTUSSIS ANTIBODY RESPONSES. There was no evidence of
hyporesponsiveness to the pertussis antigens at any time point
assessed in infants who received aP at birth compared with
control infants. All initially seronegative subjects in the aP
group became seropositive after the first dose of DTaP-HBVIPV/Hib, whereas 2 doses of DTaP-HBV-IPV/Hib were
required to reach 100% seropositivity to all pertussis antigens
in the HBV group (Table I). Vaccine response to the 3
pertussis antigens was observed in over 98% of the subjects.
One month after the first dose of DTaP-HBV-IPV/Hib,
all subjects in the aP group were seropositive for anti-PT and
anti-FHA antibodies, and 98% for anti-PRN antibodies,
compared with 46.9%, 95.9%, and 93.9% respectively, in the
HBV group. The difference between groups was statistically
significant for PT (P .001, 2-sided Fisher exact test).
Antibody GMCs for all three pertussis antigens were significantly higher after the first DTaP-HBV-IPV/Hib dose in
subjects who had received a birth dose of aP than in the HBV
group (Figure 1). Infants primed with aP remained seropositive for all pertussis antigens, with significantly higher antiFHA antibody GMCs, at all time points.
ANTIBODY RESPONSES TO OTHER VACCINE ANTIGENS. One
month after completing the primary vaccination course, all
subjects in both groups were seroprotected against diphtheria, tetanus and polio types 1, 2 and 3 (Table II). There were
no statistically significant differences between groups in postprimary vaccination antibody GMC/GMT for these 5 antigens. The administration of an additional birth dose of HBV
resulted in statistically higher seroprotection rates and anti658

Knuf et al

body GMCs against HBV compared with the aP group.

Both, seroprotection rates and antibody GMCs against Hib
were statistically significantly lower in the aP group (P .05,
with 2-sided Fisher exact test for rates, and 1 excluded from
95% CI for GMC ratio).

DISCUSSION
This study is the first to assessed the feasibility of a
stand-alone aP vaccine for immunization of newborns. The
aP vaccine was well tolerated and the safety profile of a birth
dose was similar to that of a neonatal dose of a licensed HBV
vaccine. No impact of the birth dose on the reactogenicity of
the primary vaccination course was detected during this study.
Large swelling reactions are known to occur after repeated
doses of DTaP and other vaccines,8 but in this study, they
were observed neither in subjects who had received four doses
of aP-containing vaccine by 7 months of age, nor in control
infants. Given the reported incidence of 1% to 6% of such
swellings,8,9 further studies will be needed to assess the impact
of a birth dose of aP on this type of reaction after subsequent
vaccine doses. Two other clinical trials with combined DTaP
vaccines in newborn infants led to similar observations.7,10,11
Immunogenicity results of 2 prior studies were disparate. When infants were immunized at birth with a 3-component-pertussis DTaP vaccine, which contained PRN and
FHA (2.5 g) and genetically inactivated PT (5 g) adjuvanted on aluminium hydroxide (Acelluvax, Biocine), evidence of early immunization was shown, without inducing
higher antibody responses than in control infants at the end of
the primary series.7 In contrast, when a 5-pertussis-component DTaP-vaccine was administered at birth concomitantly
with HBV, antibody responses to PT, FIM (fimbriae), and
PRN were significantly lower after the primary vaccination
course.10,11 The reduced responses to pertussis antigens persisted
after the booster dose, reminiscent of the persisting attenuated
responses seen in the earlier studies using DTwP.4,5
Using a 3-component aluminium hydroxide-adsorbed
stand-alone aP vaccine administered at birth, we have shown
no evidence for immune hyporesponsiveness to pertussis after
vaccination, but strong evidence that antibody response to B
pertussis antigens was accelerated in subjects who had received
aP at birth. Antibody GMCs were significantly higher in the
aP-at-birth-group at 3 months of age for all pertussis antiThe Journal of Pediatrics May 2008

Figure 1. Anti-pertussis antibody GMCs from birth until completion

of primary vaccination (ATP cohort for immunogenicity).
, Group
aP; , group HBV. *95% CI on the GMC ratio between groups does
not include 1.

bodies. This advantage persisted for all pertussis antigens

until 5 months of age and for FHA thereafter. The magnitude
of the antibody responses after 2 doses of aP-containing
vaccine at 0 and 2 months was lower than two DTaP-HBVIPV/Hib doses administered at 2 and 4 months in terms of

PT and PRN responses. Although an influence of the additional vaccine antigens on these results cannot be excluded, it
is reasonable to assume that the higher antibodies reflect the
increasing B-cell response capacity that is acquired in infancy
through the progressive maturation of the human immune
system.12 By 7 months of age, GMCs of antibodies against
the aP vaccine antigens were similar in both groups, with the
exception of anti-FHA antibodies, which remained significantly higher in the aP group. Adding an early aP dose to the
primary 3-dose pertussis immunization series did not markedly increase final antibody responses. This may reflect the
fact that high levels of pre-existing antibodies at the time of
vaccination, whether of maternal or infant origin, bind to
vaccine epitopes and mask them to infant B lymphocytes,13
thus reducing further immune responses.
There is no clear explanation for the markedly different
results observed in these trials. Maternal antibody levels in
newborns were not dissimilar in all 3 studies. It thus seems
likely that the different responses were a result of the vaccine
formulations (number and types of vaccine antigens administered at birth and adjuvants used) or of the additional HBV
dose used by Halasa et al.10
The mechanisms inducing protection from pertussis are
not well understood, and there is no generally accepted seroprotective antibody concentration after pertussis or pertussis vaccination. Protection from pertussis conferred by vaccination is at least partly dependent on cell-mediated immunity,
and the meaning of lower antibody concentrations with regard to vaccine efficacy is unknown.
Not unexpectedly after a birth dose of HBV vaccine,
higher seroprotection rates and antibody GMCs for HBV
were observed in the HBV group.14 The response of the
aP-at-birth-group, although showing over 90% seroprotection, is, however, at the low end of the observed response in
a 2-4-6 month schedule.15 Given the additional HBV dose
given to the control group, it is not possible to establish in this
study if the aP dose given at birth had an effect on the
immune response to HBV.
Seroprotection rates and antibody GMCs for Hib also
were lower in the aP group at the end of the primary vaccination series. Thus, neonatal pertussis immunization interfered in part with responses to Hib-tetanus toxoid conjugate
vaccine that were subsequently elicited by the DTaP-IPVHBV/Hib formulation. The lack of visible interference of the
neonatal immunization against pertussis on other vaccine
components suggests a direct influence of pertussis responses
on the immune response to Hib. This could result from a
number of immune mechanisms. Our favored hypothesis is
that the first dose of DTaP-IPV-HBV/Hib reactivated strong
secondary pertussis responses that interfered with the induction of primary Hib responses. Within the microenvironment
of the lymph node, strong secondary T-lymphocyte pertussis
specific cytokine responses may have interfered with the induction of the CD4 T-lymphocyte help required for Hib
responses but not with CD4 T-lymphocytes specific for the
other protein antigens (so-called bystander interference).

Neonatal Vaccination with an Acellular Pertussis Vaccine Accelerates the Acquisition of Pertussis Antibodies in Infants

659

Table II. Immune responses 1 month after completion of primary vaccination (ATP cohort for immunogenicity)
Group aP
Antibody
HBs
Hib
Diphtheria
Tetanus
Polio 1
Polio 2
Polio 3

Group HBV

Cutoff

GMC/T

95% CI

GMC/T

95% CI

10 mIU/mL
0.15 g/mL
1 g/mL
0.1 IU/mL
0.1 IU/mL
1:8
1:8
1:8

53
53
53
53
52
51
48
48

90.6*
88.7
49.1*
100
100
100
100
100

310.7*
0.942*

0.923
2.052
263.1
182.1
595.9

182.4; 529.2
0.632; 1.403

0.74; 1.152
1.685; 2.498
163.1; 424.7
109.4; 303.1
359.2; 988.7

55
55

100*
98.2
69.1
98.2
100
100
100
100

1684.3*
2.353*

1.175
2.852
381.3
305.6
654.0

1234.3; 2298.4
1.585; 3.493

0.890; 1.552
2.348; 2.498
252; 576.9
199.1; 469
392.6; 1089.6

55
55
54
55
54

%, Percentage of subjects with concentration above the specified cutoff.

*Statistically significant difference between groups (P .05 with 2-sided Fisher exact test for seroprotection rates, 95% CI for the group GMC/T ratio does not include 1 for the
GMC/T).

In summary, vaccination of newborn infants at age 2 to

5 days with an aP vaccine was safe and showed a low reactogenicity compared with a neonatal dose of HBV vaccine.
Recipients of aP at birth mounted an accelerated immune
response to all pertussis vaccine antigens by the age of 3
months. Because it has been observed that the risk of death
due to infection with B pertussis is reduced by the first infant
dose of aP (at 2 months of age),16 our data are encouraging
that the risk could be reduced by a birth dose.
The authors would like to thank Johann Ambrugeat and Alix
Collard for performing statistical analyses and Julia Donnelly for
editorial assistance in the preparation of this manuscript. We are
also grateful to the parents and infants who participated in the
study, the research staff and the general pediatricians.

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The Journal of Pediatrics May 2008

Figure 2. Solicited symptoms during 8-day follow-up after each dose

(total vaccinated cohort). A, Birth dose of aP or HBV; B, overall doses.

Neonatal Vaccination with an Acellular Pertussis Vaccine Accelerates the Acquisition of Pertussis Antibodies in Infants

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