Immunogenicity, Safety, and Tolerability of a Hexavalent Vaccine in Infants
BACKGROUND: DTaP5-IPV-Hib-HepB is a fully liquid investigational hexavalent vaccine directed against 6 diseases.
METHODS: This multicenter, open-label, comparator-controlled, phase III study randomly assigned healthy infants 2-to-1 as follows: group 1 received DTaP5-IPV-Hib-HepB, PCV13, and RV5 at 2, 4, and 6 months of age followed by DTaP5, Hib-OMP, and PCV13 at 15 months of age; group 2 received DTaP5-IPV/Hib, PCV13, and RV5 at 2, 4, and 6 months of age, with HepB at 2 and 6 months of age, followed by DTaP5, Hib-TT, and PCV13 at 15 months of age.
RESULTS: Overall, 981 participants were vaccinated in group 1 and 484 in group 2. Immune responses in group 1 to all antigens contained in DTaP5-IPV-Hib-HepB 1 month after dose 3 and for concomitant rotavirus vaccine were noninferior to those in group 2, with the exception of antipertussis filamentous hemagglutinin (FHA) geometric mean concentrations (GMCs). Vaccine response rates for FHA were noninferior to control. After the toddler dose, group 1 immune responses were noninferior to group 2 for all pertussis antigens. Solicited adverse event rates after any dose were similar in both groups, with the exceptions of increased injection-site erythema, increased fever, and decreased appetite in group 1. Fever was not associated with hospitalization or seizures.
CONCLUSIONS: The safety and immunogenicity of DTaP5-IPV-Hib-HepB are comparable with the analogous licensed component vaccines. Decreased FHA GMCs and increased injection-site reactions and fever are unlikely to be clinically significant. DTaP5-IPV-Hib-HepB provides a new combination vaccine option aligned with the recommended US infant immunization schedule.
- AE —
- adverse event
- CI —
- confidence interval
- DT —
- diphtheria toxoid
- FHA —
- pertussis filamentous hemagglutinin
- FIM-2,3 —
- pertussis fimbriae types 2 and 3
- GMC —
- geometric mean concentration
- HBsAg —
- hepatitis B surface antigen
- Hib —
- invasive Haemophilus influenzae type b
- IgA —
- immunoglobulin A
- IM —
- IPV —
- inactivated polio vaccine
- PRN —
- pertussis pertactin
- PRP —
- polyribosylribitol phosphate
- PT —
- pertussis toxoid
- SAE —
- serious adverse event
- TT —
- tetanus toxoid
What’s Known on This Subject:
The routine childhood immunization schedule is crowded during the first 2 years, leading to deferred doses and limiting the addition of new vaccines. Combination vaccines can reduce the “shot burden” and improve coverage rates and timeliness.
What This Study Adds:
Antibody response rates to antigens contained in an investigational hexavalent vaccine (DTaP5-IPV-Hib-HepB) were noninferior to licensed comparator vaccines when given as a 3-dose infant series. The safety profile was similar to control except for increased rates of mild-to-moderate, self-limited fever.
The recommended immunization schedule for children in the United States protects infants and toddlers against 14 different diseases.1 Without the use of modern combination vaccines such as DTaP3-HepB-IPV and DTaP5-IPV/Hib, the schedule would call for as many as 25 separate injections (27 or 28 separate vaccinations including RV1 or RV5) in the first 2 years of life (see the Appendix for vaccine abbreviations and manufacturers).2 Even with current combination vaccines, however, the “shot burden” is still appreciable: a minimum of 18 injections (20 separate vaccinations) in the first 2 years of life.2 The high injection density during these early years is a factor in vaccine hesitancy, leading to the perception that infants receive “too many shots too soon,”3 with downstream consequences including deferred doses and decreased coverage rates.4,5 Moreover, the crowded vaccination schedule makes it difficult to add new vaccines with potential incremental health benefits to young children. For all of these reasons, the Advisory Committee on Immunization Practices,6 American Academy of Pediatrics,7 and American Academy of Family Physicians8 all endorse the use of combination vaccines.
Higher valency combination vaccines have the potential to mitigate these issues and have been shown to improve coverage and timeliness.9–11 The investigational hexavalent vaccine DTaP5-IPV-Hib-HepB is a fully liquid combination vaccine directed against 6 diseases; incorporating it into the childhood schedule would result in 1 to 4 fewer shots, depending on which DTaP-based combination vaccine was previously used, which monovalent invasive Haemophilus influenzae type b (Hib) vaccine was used along with DTaP3-HepB-IPV, and whether the toddler dose was delivered as DTaP plus monovalent Hib or DTaP5-IPV/Hib. This report presents results from the pivotal US phase III study (NCT01337167), assessing the safety, tolerability, and immunogenicity of DTaP5-IPV-Hib-HepB compared with DTaP5-Hib-IPV plus HepB when administered concomitantly with PCV13 and RV5.
Healthy infants 46 to 89 days of age who had received 1 dose of hepatitis B vaccine (outside of study) before or at 1 month of age were eligible for the study. Participants were excluded if they had (1) participated in another study of an investigational compound or device within 4 weeks of entry, or planned to enroll in another clinical study during the current study period; (2) received or expected to receive immunosuppressive agents; (3) received systemic steroids (equivalent of >2 mg/kg per day prednisone) since birth, within 7 days before study entry, or expected to receive steroids through the course of the study; (4) a history of leukemia, lymphoma, malignant melanoma, or myeloproliferative disorder; (5) known or suspected hypersensitivity to any vaccine component; (6) received >1 dose of hepatitis B vaccine or >1 combination vaccine containing hepatitis B vaccine; (7) received any vaccines other than hepatitis B vaccine; (8) a febrile illness, or a rectal temperature ≥38.0°C (≥100.4°F), within 24 hours before enrollment; (9) a coagulation disorder contraindicating intramuscular (IM) vaccination; (10) a maternal or personal history of hepatitis B surface antigen (HBsAg) seropositivity; (11) a history of Hib disease, hepatitis B, diphtheria, tetanus, pertussis, poliomyelitis, rotavirus gastroenteritis, or pneumococcal disease; or (12) any contraindication to the concomitant study vaccines. Prematurity was not an exclusion criterion. The protocol was conducted in accordance with principles of Good Clinical Practice, including obtaining written informed consent from each participant’s parent or legal guardian before study entry, and was approved by the human studies committees applicable to each study site.
Table 1 displays characteristics of the vaccines used in this study. Vaccine supplies were shipped, stored, and distributed in accordance with the study protocol and Good Manufacturing Practice. Of note, DTaP5-IPV-Hib-HepB was presented in a sterile, single-dose, liquid, preservative-free formulation. All vaccine doses were 0.5 mL given intramuscularly, except for RV5, which was 2.0 mL given orally.
This was a randomized, open-label, active comparator-controlled study conducted at 40 sites in the United States between April 2011 and May 2013. A total of 1473 healthy infants were randomly assigned by using a computer-generated, site-balanced allocation schedule to receive either DTaP5-IPV-Hib-HepB (group 1) or control vaccines (group 2) in a 2:1 ratio (Table 2). Participants in group 1 received DTaP5-IPV-Hib-HepB, PCV13, and RV5 at 2, 4, and 6 months of age followed by DTaP5, Hib-OMP, and PCV13 at 15 months of age. Participants in group 2 received DTaP5-IPV/Hib, PCV13, and RV5 at 2, 4, and 6 months of age, as well as HepB at 2 and 6 months of age, followed by DTaP5, Hib-TT, and PCV13 at 15 months of age. The Hib vaccine administered at 15 months of age was chosen to preserve the same Hib antigen-conjugate for the entire Hib vaccination series (Hib-OMP contains the same protein-polysaccharide conjugate as the Hib component of DTaP5-IPV-Hib-HepB, and Hib-TT contains the same protein-polysaccharide conjugate as the Hib component of DTaP5-IPV/Hib).
Blood specimens used to assess immunogenicity were collected via venipuncture immediately before administration of dose 1, ∼1 month after completion of the infant series (dose 3), immediately before the toddler dose, and ∼1 month after the toddler dose.
From day 1 (day of vaccination) to day 5 after each vaccination, the following safety measurements were obtained: temperature; solicited injection-site adverse events (AEs), including injection-site pain, tenderness, redness, and swelling; and solicited systemic AEs, including pyrexia (fever), vomiting, abnormal crying, drowsiness, appetite loss, and irritability. Unsolicited injection-site and systemic AEs were collected through day 15 after each vaccination. Serious AEs (SAEs), defined as AEs leading to hospitalization, were recorded from study entry up to 6 months after the last DTaP5-IPV-Hib-HepB vaccination, regardless of causality.
Parents were instructed to not administer antipyretic, analgesic, or nonsteroidal antiinflammatory medications within 48 hours before administration of study vaccines; these medications were allowed after vaccination in response to fever.
Live attenuated vaccines, such as varicella, measles, mumps, and rubella vaccines, were not provided as part of the study, but were permitted as long as they were given more than 30 days before or after any dose of study vaccine. Nonstudy inactivated vaccines, including inactivated influenza vaccine, were permitted more than 14 days before or after any dose of study vaccine.
The primary objectives were to (1) compare the immunogenicity of DTaP5-IPV-Hib-HepB with the corresponding control vaccines; (2) compare the immunogenicity of pertussis responses 1 month after the toddler dose of DTaP5 in children whose primary pertussis series was 3 doses of DTaP5-IPV-Hib-HepB versus 3 doses of DTaP5-IPV/Hib; and (3) demonstrate that the poliovirus response rate is acceptable after 3 infant doses of DTaP5-IPV-Hib-HepB.
The secondary objectives were to (1) compare antibody responses to polyribosylribitol phosphate (PRP; the polysaccharide antigen component of Hib conjugate vaccines) elicited by DTaP5-IPV-Hib-HepB versus the corresponding control vaccines; (2) evaluate the immunogenicity of RV5 when administered concomitantly with DTaP5-IPV-Hib-HepB; (3) describe the per-dose safety profile of DTaP5-IPV-Hib-HepB and the control vaccines when given concomitantly with PCV13 and RV5; (4) describe the fever profile after any dose of DTaP5-IPV-Hib-HepB and control vaccines when given concomitantly with PCV13 and RV5; (5) describe the percentage of participants with solicited injection-site and systemic AEs within 5 days after any dose of DTaP5-IPV-Hib-HepB or control vaccines when coadministered with other recommended vaccines; and (6) describe the incidence of SAEs up to 6 months after the last dose of DTaP5-IPV-Hib-HepB or control vaccines.
The tertiary objectives were to describe (1) the geometric mean concentrations (GMCs) of antibody against all antigens in DTaP5-IPV-Hib-HepB and corresponding control vaccines after 3 doses; (2) the proportion of participants with anti-PRP concentration ≥ 0.15 μg/mL (considered the short-term correlate of protection12,13) before the toddler dose of Hib-OMP or Hib-TT and the proportion of participants with anti-PRP ≥ 1.0 μg/mL (considered the long-term correlate of protection12,13) 1 month after the toddler dose of either vaccine; and (3) the response rates to all antigens except pertussis 1 month after the toddler dose.
The study planned to enroll ∼1440 subjects (960 in group 1 and 480 in group 2). Assuming 85% of the randomly assigned subjects were evaluable after dose 3 and 80% 1 month after the toddler dose, the study had ∼92.6% power for testing all the primary objectives.
Antibody responses were defined based on accepted immune correlates of protection,14 or previously accepted definitions of vaccine response for licensed vaccines (Supplemental Table 8). The primary and key secondary end points, analysis populations, and statistical methods for immunogenicity analyses are provided in Supplemental Table 9. The per-protocol analyses included all participants who met the inclusion criteria, did not deviate from the protocol, and had serology results within the specified day ranges. The per-protocol, original windows population consisted of the per-protocol population who had vaccination windows of 46 to 74 days after the previous vaccination and blood draw sample windows of 28 to 44 days after the infant series (dose 3) or toddler dose. The per-protocol, revised windows population consisted of the per-protocol population who had vaccination windows of 42 to 84 days after the previous vaccination and blood draw sample windows of 28 to 51 days after the infant series (dose 3) or toddler dose. The revised windows were prespecified in an amendment to the protocol and statistical analysis plan before database lock and knowledge of immunogenicity results. They were based on earlier phase II studies of DTaP5-IPV-Hib-HepB and allowed for inclusion of immunogenicity data from more vaccinated participants in the per-protocol analysis. The success of immunogenicity hypothesis testing was based on results from the per-protocol, revised windows population. Key immunogenicity summaries and analyses were also provided for all end points associated with hypotheses by using the full analysis set population, which included all randomly assigned participants with available serology data at postvaccination regardless of protocol deviation.
All randomly assigned participants who received ≥1 dose of study vaccine and had safety follow-up were included in the safety analysis. The AE and fever profiles were described for study vaccines after each vaccination and the entire vaccination period. Incidence rates of solicited AEs (days 1 to 5 after any infant dose), elevated temperatures (≥38°C, days 1 to 5 after any infant dose), and unsolicited AEs (days 1 to 15 after any infant dose and occurring in more than 1% of the participants in either vaccination group), were compared by using point estimates and 95% confidence interval (CI; unstratified Miettinen and Nurminen method).15 Other safety end points were summarized by using frequency counts and percentages.
Participant Accounting and Demographics
As shown in Fig 1, 1237 (83.9%) randomly assigned participants completed the study. Participants in both groups were comparable with respect to baseline characteristics (Table 3). The most common underlying medical conditions were neonatal jaundice (27.5% of group 1, 27.7% of group 2) and gastroesophageal reflux disease (19.2% of group 1, 21.9% of group 2). The most frequently reported concomitant medications administered during the study were analgesics (64.0% of group 1, 60.1% of group 2) and antiinflammatory products (26.1% of group 1, 21.5% of group 2).
Antibody response rates after the infant series for all antigens contained in DTaP5-IPV-Hib-HepB are shown in Fig 2. One month after the infant series, the lower bound of the 2-sided 95% CI for the group difference in response rates (group 1 minus group 2) was above the prespecified noninferiority margins for all antigens. GMCs of antibody responses to pertussis antigens, PRP, and rotavirus after the infant series and for pertussis antigens after the toddler dose are given in Table 4. The GMC ratio (group 1/group 2) was above the prespecified noninferiority margin for all antibodies except for pertussis filamentous hemagglutinin (FHA).
Antibody response rates and GMCs to pertussis antigens after the toddler dose are shown in Fig 3 and Table 4, respectively. The lower bounds of the 2-sided 95% CI for response rates (group 1 minus group 2) and GMC ratios (group 1/group 2) were above noninferiority margins, indicating that both response rates and GMCs in group 1 were noninferior to group 2 for all pertussis antibodies 1 month after the toddler dose.
Figure 2 also reveals antibody response rates to poliovirus antigens after the infant series. The lower bound of the 2-sided 95% CI for the response rates in group 1 was ≥90%, indicating that responses for poliovirus types 1, 2, and 3 were acceptable. In addition, Fig 2 reveals anti-PRP response rates after the infant series. The estimated difference in response rate at the 0.15-μg/mL level was 4.87% (95% CI: 2.23 to 8.14), satisfying the criterion for noninferiority (>−5%). At the 1.0-μg/mL level, the estimated difference was 9.68% (95% CI: 4.83 to 14.83), which also met the prespecified noninferiority criterion (>−10%).
Table 4 also reveals GMCs of antibody responses to concomitantly administered RV5 after the infant series. The lower bound of the 95% CI for the GMC ratio (group 1/group 2) of antirotavirus immunoglobulin A (IgA) was 0.83, satisfying the noninferiority criterion (>0.67).
Results discussed in this section refer to the per-protocol, revised windows population; results on the basis of the per-protocol, original windows and full analysis set populations were consistent with the results for per-protocol, revised windows for all immunogenicity end points.
Safety follow-up was obtained for ≥99% of participants in each group. As seen in Table 5, 95.5% of participants in group 1 and 93.4% in group 2 reported ≥1 AE after any dose in the infant vaccination series. In general, the proportion of participants reporting injection-site AEs (days 1–15), solicited injection-site AEs (days 1–5), systemic AEs (days 1–15), and solicited systemic AEs (days 1–5) were similar between groups 1 and 2. The most notable exceptions were solicited reports of decreased appetite on days 1 to 5, which were more common in group 1 (48.9%) than group 2 (43.4%), and solicited reports of pyrexia on days 1 to 5, which were more common in group 1 (47.4%) than group 2 (34.4%). Most of these reports were mild to moderate in intensity and did not lead to medical intervention. During the entire study, 1 participant in group 1 and 1 participant in group 2 discontinued because of vaccine-related non-SAEs.
Table 5 also reveals that 5.4% of participants in group 1 and 6.4% of participants in group 2 reported at least 1 SAE after any dose in the infant vaccination series. There were no discontinuations because of vaccine-related SAEs. One participant in group 1 and 1 in group 2 died during the study; neither death was considered by the investigator to be related to study vaccinations.
Fever of any degree after any infant series vaccine dose was more common in group 1 than group 2 (Table 6, difference 13.1 [7.7%–18.4%]). This was due to a statistically significantly higher incidence of mild and moderate fever in group 1. However, the rates of severe fever were not statistically significantly different. Fever was of brief duration (≤2 days for the vast majority), and fever-related SAEs were rare and similar between groups (Table 7).
In this large, randomized, open-label, multicenter, controlled clinical trial, antibody response rates to the 12 antigens (diphtheria toxoid [DT], tetanus toxoid [TT], pertussis toxoid [PT], FHA, pertussis pertactin [PRN], pertussis fimbriae types 2 and 3 [FIM-2,3; considered as 2 antigens], inactivated polio vaccine [IPV] 1, IPV2, IPV3, PRP, and HBsAg) contained in DTaP5-IPV-Hib-HepB were noninferior to those for licensed comparators when the vaccines were given as a 3-dose infant series. IgG antibody GMCs to all of the antigens except pertussis FHA were also noninferior. However, antibody response rates and GMCs to all pertussis antigens were noninferior to control after the toddler dose of DTaP5. These results suggest that efficacy against the respective diseases (diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B) would be expected to be similar to the demonstrated efficacy of the licensed comparator vaccines. Responses to rotavirus vaccine given with DTaP5-IPV-Hib-HepB were noninferior to responses when given with control vaccine. Overall, 26 of 27 primary immunogenicity end points in this study were met. The failure to meet noninferiority criteria for FHA GMC after the infant series, while meeting criteria for postinfant series response rate and for both response rate and GMC after the toddler dose, is likely of no clinical significance, especially because the other pertussis components (PT, PRN, and FIM-2,3) have been more clearly correlated with pertussis protection.14,16–18 In a previous phase IIB study, over 70% of subjects receiving DTaP5-IPV-Hib-HepB achieved a fourfold rise in antibody responses to PT, FHA, PRN, and FIM-2,3, but acceptability criteria for FHA and PRN were not met.16
The safety profile of DTaP5-IPV-Hib-HepB was similar to control and in line with that expected for routine childhood vaccines. It is noteworthy that DTaP5-IPV-Hib-HepB administration was associated with increased rates of mild and moderate, self-limited fever that was not associated with an increase in fever-related medical events. Increased rates of fever have been noted before with multivalent combination vaccines. For example, prelicensure studies revealed higher rates of fever (solicited temperature ≥38°C) among infants given DTaP3-HepB-IPV plus PCV7 as compared with those given the corresponding component vaccines plus PCV7, although higher fever (temperature ≥39.5°C) was rare and occurred with similar frequency in both groups.19 There was some concern early on that increased rates of even low-grade fever might prompt emergency department visits, invasive diagnostic workups, and hospital admissions.20 However, in a managed care-based cohort study of over 61 000 infants who received DTaP3-HepB-IPV (a total of 120 000 doses) plus PCV7, there was no increase in medically attended events associated with fever, including seizure, as compared with a historical control that received the component vaccines.21 In this context, it is worth noting that high temperatures (≥39.5°C) occurred in only 2% of infants who received DTaP5-IPV-Hib-HepB in the current study. Fever-related AEs were also rare. As with other licensed vaccines, the safety profile of DTaP5-IPV-Hib-HepB will be monitored after approval.
Virtually all doses of DTaP in the United States are given to infants as either DTaP3-HepB-IPV or DTaP5-IPV/Hib, both 5-valent combination vaccines.22 In contrast, a DTaP-based hexavalent vaccine has been used in Europe for over a decade.23 Its adoption was associated with improved immunization timeliness24 and no decrement in effectiveness in preventing disease.25 Adoption of a hexavalent combination vaccine in the United States might result in similar benefits: improved coverage and timeliness, sustained protection against disease, and “room” in the schedule for introduction of new vaccines. Given the data presented herein, DTaP5-IPV-Hib-HepB would be an attractive addition to the vaccine armamentarium in the United States.
Appendix: Vaccine Abbreviations, Trade Names, and Manufacturers
DTaP3-HepB-IPV: diphtheria and tetanus toxoids and acellular (3-component) pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine (Pediarix™; GlaxoSmithKline, Rixensart, Belgium).
DTaP5: diphtheria and tetanus toxoids and acellular (5-component) pertussis vaccine absorbed (Daptacel™; Sanofi Pasteur, Swiftwater, PA).
DTaP5-IPV/Hib: diphtheria and tetanus toxoids and acellular (5-component) pertussis absorbed, inactivated polio, and Haemophilus b conjugate (tetanus toxoid conjugate) vaccine (Pentacel™; Sanofi Pasteur).
DTaP5-IPV-Hib-HepB: diphtheria, tetanus, acellular pertussis (5-component), inactivated polio, Haemophilus influenzae type b (polyribosylribitol phosphate-Neisseria meningitidis outer membrane protein conjugate), and hepatitis B vaccine (investigational hexavalent vaccine).
HepB: hepatitis B vaccine (recombinant; Recombivax HB™; Merck, Kenilworth, NJ).
Hib-OMP: Haemophilus b conjugate vaccine (meningococcal protein [N meningitidis serogroup B outer membrane protein] conjugate; PedvaxHIB™; Merck).
Hib-TT: Haemophilus b conjugate vaccine (tetanus toxoid conjugate; ActHIB™; Sanofi Pasteur).
IPV: inactivated polio vaccine (no trade name; used as a component of combination vaccines by various manufacturers).
PCV7: pneumococcal 7-valent conjugate vaccine (diphtheria CRM197 protein; Prevnar™; Pfizer, Philadelphia, PA).
PCV13: pneumococcal 13-valent conjugate vaccine (diphtheria CRM197 protein; Prevnar 13™; Pfizer).
RV1: rotavirus vaccine, live, oral (monovalent; Rotarix™; GlaxoSmithKline).
RV5: rotavirus vaccine, live, oral, pentavalent (RotaTeq™; Merck).
The V419 Protocol 005 Study Group participants were as follows: Alabama: Claude Ashley, William H. Johnson; Arkansas: Anthony D. Johnson, Tracy D. Stewart; California: Nicola Klein; Colorado: Robin L. Schaten; Connecticut: Timothy J. Sullivan; Georgia: Wilson P. Andrews; Kansas: Robyn D. Hartvickson, Paul A. Klaassen; Kentucky: Stanley L. Block, Christopher A. Cunha, Gary S. Marshall; Louisiana: Frank B. Hughes, Thomas G. Latiolais; New York: Robert A. Dracker; North Carolina: Gregory L. Adams, Earl R. Franklin, Karin R. McLelland; Ohio: Julie Shepard; Pennsylvania: Cheryl Duffy, Richard T. Kratz, Anthony P. LaBarbera, Keith S. Reisinger, Edward P. Rothstein, Steven A. Shapiro, David A. Wyszomierski, Ann M. Zomcik; South Carolina: Michael L. Leonardi, Abe H. Moskow; Tennessee: Donald H. Lewis, Joseph A. Ley; Texas: Khozema A. Palanpurwala; Utah: Matthew J. Cornish, Matthew N. Cox, Martin A. Hollingsworth, Peter E. Silas, Kenneth A. Zollo; and Washington: Timothy E. Crum, Stephen R. Luber.
We thank all of the study participants, their parents, the study investigators, and their staff. We also thank Dr David R. Johnson of Sanofi Pasteur for helpful review of the draft manuscript and Mrs Karyn Davis for her assistance during author review and submission.
- Accepted May 27, 2015.
- Address correspondence to Andrew W. Lee, MD, Merck & Co, Inc, 2000 Galloping Hill Rd, UG-3D063, Kenilworth, NJ 08889. E-mail:
Dr Marshall and Mr Stek drafted the initial manuscript; Drs Marshall, Adams, and Leonardi contributed to participant enrollment, data collection/acquisition, data interpretation, and they reviewed and revised the manuscript; Drs Flores, Xu, Liu, Foglia, and Lee contributed to the study concept/design, data analysis/interpretation, and they reviewed and revised the manuscript; Mrs Petrecz, Ms Ngai, and Mr Stek contributed to the data analysis/interpretation, and they reviewed and revised the manuscript; and all authors approved the final manuscript as submitted.
Data from this article were presented in poster format (#1112) at IDWeek-2014 in Philadelphia, PA.
Although the sponsors formally reviewed a penultimate draft, the opinions expressed are those of the authors and may not necessarily reflect those of the sponsors.
FINANCIAL DISCLOSURE: Dr Marshall has been an investigator on clinical trials funded by GlaxoSmithKline, Merck, Novartis, Pfizer, and Sanofi Pasteur, and he also has received honoraria from these companies for service on advisory boards; Dr Adams reports that his major revenue source is private insurance payments and receipts from Medicaid for medical services rendered caring for children in a private pediatric practice, which includes routine recommended immunizations; Drs Marshall, Adams, and Leonardi were investigators for the sponsor supported by research grants; and Mrs Petrecz, Dr Flores, Ms Ngai, Drs Xu and Liu, Mr Stek, and Drs Foglia and Lee are employees of the sponsors and may hold stock and/or stock options from the sponsors.
FUNDING: Funding for this research was provided by Merck & Co, Inc, and Sanofi Pasteur, Inc (sponsors).
POTENTIAL CONFLICT OF INTEREST: Dr Marshall has been an investigator on clinical trials funded by GlaxoSmithKline, Merck, Novartis, Pfizer, and Sanofi Pasteur, and he also has received honoraria from these companies for service on advisory boards; Dr Adams reports that his major revenue source is private insurance payments and receipts from Medicaid for medical services rendered caring for children in a private pediatric practice, which includes routine recommended immunizations; Drs Marshall, Adams, and Leonardi were investigators for the sponsor supported by research grants; and Mrs Petrecz, Dr Flores, Ms Ngai, Drs Xu and Liu, Mr Stek, and Drs Foglia and Lee are employees of the sponsors and may hold stock and/or stock options from the sponsors.
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- Copyright © 2015 by the American Academy of Pediatrics