Grading of Recommendations, Assessment, Development, and Evaluation (GRADE): Use of Haemophilus influenzae Type b-Containing Vaccines among American Indian and Alaska Native Infants

About

CDC vaccine recommendations are developed using an explicit evidence-based method based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Introduction

On December 21, 2018, the U.S. Food and Drug Administration licensed a hexavalent combined diphtheria and tetanus toxoids and acellular pertussis (DTaP) adsorbed, inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) conjugate, and hepatitis B (HepB) recombinant vaccine, DTaP-IPV-Hib-HepB (Vaxelis, MSP Vaccine Company (a U.S.-based partnership between Merck, known as MSD outside the United States and Canada, and Sanofi)) for use as a 3-dose series in infants at ages 2, 4, and 6 months.1 On June 26, 2019, CDC's Advisory Committee on Immunization Practices (ACIP) voted to include DTaP-IPV-Hib-HepB in the federal Vaccines for Children (VFC) program.2 This decision was based on review of data from clinical trials comparing immunogenicity and safety of DTaP-IPV-Hib-HepB and licensed comparator vaccines among healthy infants in the general U.S. population.

Hib vaccination with monovalent PRP-OMP (PedvaxHIB, Merck & Co, Inc.) has been preferred for American Indian/Alaska Native infants because it provides a protective antibody response after the first dose.3 This is important because before routine Hib vaccination began, the incidence of H. influenzae meningitis peaked at a younger age among American Indian/Alaska Native infants (4–6 months) than among other U.S. infant populations (6–7 months)4. Vaxelis contains PRP-OMP but the dose is lower than PedvaxHIB, and data on post-dose 1 antibody responses were not previously available. At the time of the VFC vote for DTaP-IPV-Hib-HepB, ACIP did not include it in the preferential recommendation for American Indian/Alaska Native infants given the lack of post-dose 1 immunogenicity data.

Given recently available data comparing post-dose 1 immunogenicity of DTaP-IPV-Hib-HepB and monovalent PRP-OMP among American Indian/Alaska Native infants, ACIP re-evaluated the Hib vaccine preferential recommendation for American Indian/Alaska Native infants. A systematic review and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to inform ACIP's deliberations regarding use of DTaP-IPV-Hib-HepB among American Indian and Alaska Native infants. The policy question under consideration was "Should DTaP-IPV-Hib-HepB (Vaxelis) be included with monovalent PRP-OMP (PedvaxHIB) in the preferential recommendation for American Indian/Alaska Native infants based on the Haemophilus influenzae type b (Hib) component"? (Table 1).

Methods

Members of ACIP's Meningococcal/Hib Vaccines Work Group ("Work Group") selected the policy question and specified and rated the importance of relevant outcomes (including benefits and harms) before the GRADE assessment (Table 1, Table 2). All Work Group members and CDC staff participating in the GRADE assessment met ACIP requirements for reporting conflicts of interest.

A systematic literature search was conducted using Medline, Embase, Cochrane Library, CINAHL (EBSCOHost), Scopus, and clinicaltrials.gov databases. Efforts also were made to obtain unpublished or other relevant data. Two reviewers screened titles, abstracts, and full-text records, as indicated, to determine whether records should be included. Records were included if they presented primary data on use of DTaP-IPV-Hib-HepB among American Indian/Alaska Native infants pertinent to one or more of the PICO outcomes. Characteristics of all included studies are shown in Appendix 1, and evidence retrieval methods are shown in Appendix 2.5

The GRADE evidence certainty assessment addressed risk of bias, inconsistency, indirectness, imprecision, and other characteristics. The evidence certainty categories were high, moderate, low, or very low certainty.

Results

A summary of the GRADE assessment was presented to ACIP on June 26, 2024. Overall, 2,332 records were identified and screened; 2,290 records were excluded based on the title, and 41 records were excluded based on review of the abstract or full text. The remaining record described results from one phase IV, prospective, open-label, randomized controlled clinical trial comparing DTaP-IPV-Hib-HepB and monovalent PRP-OMP among American Indian/Alaska Native infants and was included in the evidence synthesis and GRADE assessment (Appendix 1).5 No data were identified regarding the outcome invasive Hib disease. Data on the remaining outcomes are summarized in the tables below.

Summary

For all three outcomes with available data, the initial evidence level was high because the available data were from a randomized controlled trial. For post-dose 1 immunity, the proportion of participants with anti-Hib concentration ≥0.15 µg/mL (the putative correlate of short-term protection) 30 days post-dose 1 was similar among infants in the DTaP-IPV-Hib-HepB group and the monovalent PRP-OMP group. For post-primary series immunity, the proportion of participants with anti-Hib concentration ≥1.0 µg/mL (the putative correlate of long-term protection) 150 days post-dose 1 was higher in the DTaP-IPV-Hib-HepB group than in the monovalent PRP-OMP group. Antibody titers were not available beyond day 150 post-dose 1. The proportion of serious adverse events was similar between groups, and no serious adverse events were deemed related to study participation. All outcomes were downgraded for imprecision based on wide confidence intervals surrounding the absolute risks, resulting in a final evidence certainty of moderate for each outcome.

Tables

Table 1: Policy Question and PICO

Policy question: Should DTaP-IPV-Hib-HepB (Vaxelis) be included with monovalent PedvaxHIB (PRP-OMP) in the preferential recommendation for American Indian and Alaska Native infants based on the Haemophilus influenzae type b (Hib) component?
Population American Indian and Alaska Native infants
Intervention DTaP-IPV-Hib-HepB (Vaxelis)
Comparison Monovalent PRP-OMP (PedvaxHIB)
Outcomes
  • Invasive Hib disease
  • Post-dose 1 immunity
  • Post-primary series immunity
  • Serious adverse events

Table 2: Outcomes and Rankings

Outcome Importance* Included in evidence profile
Invasive Hib disease Important No
Post-dose 1 immunity Critical Yes
Post-primary series immunity Important Yes
Serious adverse events Critical Yes

Table 3: Summary of Studies Reporting Outcomes of Interest

Table 3a: Summary of Studies Reporting Post-dose 1 Immunity (30 Days Post-Dose 1)a

Author, pub year Study population n/N
DTaP-IPV-Hib-HepB (Vaxelis)		 n/N
Monovalent
PRP-OMP (PedvaxHIB)		 Point estimate (95% CI)
DTaP-IPV-Hib-HepB (Vaxelis)		 Point estimate (95% CI)
Monovalent
PRP-OMP (PedvaxHIB)		 Effect estimateb—
(95% confidence interval)		 Study limitations (risk of bias)
Anti-Hib GMC (modeled by constrained longitudinal data analysis)
Hammitt (NCT04978818),
2024		 Navajo Nation and Alaska Native infants 167 163 0.41 (0.33–0.51) 0.40 (0.31–0.50) 1.03 (0.75–1.41) Not serious
Proportion with anti-Hib IgG concentration >0.15 µg/mL
Hammitt (NCT04978818),
2024		 Navajo Nation and Alaska Native infants 115/152 104/146 75.7% (68.2–81.8%) 71.2% (63.3–78.0%) 1.06 (0.93–1.22) Not serious
Proportion with anti-Hib IgG concentration >1.0 µg/mL
Hammitt (NCT04978818),
2024		 Navajo Nation and Alaska Native infants 38/152 40/146 25.0% (18.7–32.5%) 27.4% (20.8–35.2%) 0.91 (0.62–1.34) Not serious
Proportion with 4-fold rise in anti-Hib IgG concentration (vs. pre-dose 1)
Hammitt (NCT04978818),
2024		 Navajo Nation and Alaska Native infants 50/149 47/142 33.6% (26.0–41.5%) 33.1% (25.8–41.3%) 1.01 (0.73–1.40) Not serious

NA = not applicable

aThe median duration between first dose and the reported immunity outcomes was 34 days (interquartile range (IQR) 32–37 days) for the Vaxelis group and 34 days (IQR 31–39 days) for the PedvaxHIB group.

bThe effect estimate is the geometric mean concentration ratio for anti-Hib GMC and the risk ratio for proportions.

Table 3b: Summary of Studies Reporting Post-Primary Series Immunity (150 Days Post-Dose 1)a

Author, pub year Study population n/N
DTaP-IPV-Hib-HepB (Vaxelis)		 n/N
Monovalent
PRP-OMP (PedvaxHIB)		 Point estimate (95% CI)
DTaP-IPV-Hib-HepB (Vaxelis)		 Point estimate (95% CI)
Monovalent PRP-OMP (PedvaxHIB)		 Effect estimateb —
(95% confidence interval)		 Study limitations (risk of bias)
Anti-Hib GMC (modeled by constrained longitudinal data analysis)
Hammitt (NCT04978818),
2024		 Navajo Nation and Alaska Native infants 167 163 4.19 (3.21–5.47) 2.35 (1.78–3.10) 1.78 (1.66–2.60) Not serious
Proportion with anti-Hib IgG concentration >0.15 µg/mL
Hammitt (NCT04978818),
2024		 Navajo Nation and Alaska Native infants 122/128 106/117 95.3% (89.9–97.9%) 90.6% (83.8–94.7%) 1.05 (0.98–1.13) Not serious
Proportion with anti-Hib IgG concentration >1.0 µg/mL
Hammitt (NCT04978818),
2024		 Navajo Nation and Alaska Native infants 107/128 84/117 83.6% (76.1–89.1%) 71.8% (62.9–79.2%) 1.16 (1.02–1.34) Not serious
Proportion with 4-fold rise in anti-Hib IgG concentration (vs. pre-dose 1)
Hammitt (NCT04978818),
2024		 Navajo Nation and Alaska Native infants 95/124 85/113 76.6% (68.3–88.3%) 75.2% (66.4–82.3%) 1.02 (0.88–1.18) Not serious

NA = not applicable

aThe median duration between first dose and the reported immunity outcomes was 174 days (IQR 163–187 days) for the Vaxelis group and 180 days (IQR 162–189 days) for the PedvaxHIB group.

bThe effect estimate is the geometric mean concentration ratio for anti-Hib GMC and the risk ratio for proportions.

Table 3c: Summary of Studies Reporting Serious Adverse Eventsa

Author, pub year Age or other characteristic Type of event n/N (%)
DTaP-IPV-Hib-HepB (Vaxelis)		 n/N (%)
Monovalent PRP-OMP (PedvaxHIB)		 Effect estimate — RR (95% CI) Study limitations (risk of bias)
Hammitt (NCT04978818), 2024 Navajo Nation and Alaska Native infants All serious adverse events from the time of the first dose of study vaccine to the end of the last study visit (approximately 5 months) 9/167 (5%)b 12/166 (7%)b 0.75 (0.32–1.72) Not serious

aSafety monitoring for serious adverse events (defined as hospitalization, death, life-threatening drug experience, or prolonging of hospitalization) was performed on study day 0, 30, 60, 120, and 150.

bNumber of participants experiencing a serious adverse event are reported in the numerator. All participants in each group who received the first dose are included in the denominator. In the Vaxelis group 10 serious adverse events occurred among 9 participants. In the PedvaxHIB group, 15 Serious adverse events occurred among 12 participants. The most common serious adverse event was acute respiratory infection 21/25 (84%). No Serious adverse events were deemed related to study participation.

Table 4: Grade Summary of Findings Table

Certainty assessment № of patients Effect Certainty Importance
№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations DTaP-IPV-Hib-HepB (Vaxelis) n/N % (95% CI) Monovalent PRP-OMP (PedvaxHIB) n/N % (95% CI) Relative risk (95% CI) Absolute risk (95% CI)
Post-dose 1 immunity (assessed via proportion with anti-Hib IgG concentration ≥0.15 µg/mL 30 days post-dose 1)
1 Randomized trials Not seriousa Not serious Not seriousb,c,d Seriouse None 115/152
(75.7%)		 104/146
(71.2%)		 1.06 (0.93–1.22) 4,274 more per 100,000 (from 4,986 fewer to 15,671 more) Moderate Critical
Post-primary series immunity (assessed via proportion with anti-Hib IgG concentration ≥1.0 µg/mL 150 days post-dose 1)
1 Randomized trials Not seriousf Not serious Not seriousb,d Seriouse None 107/128
(83.6%)		 84/117
(71.8%)		 1.16 (1.02 –1.34) 11,487 more per 100,000 (from 1,436 more to 24,410 more) Moderate Important
Serious Adverse Events g
2 Randomized trials Not serioush Not serious Not seriousd Seriouse None 9/167 (5.4%) i 12/166 (7.2%) i 0.75 (0.32–1.72) 1,807 fewer per 100,000 (from 4,916 fewer to 5,205 more) Moderate Critical

aSimilar loss to follow-up for anti-Hib IgG concentration 30 days post-dose 1: Vaxelis: 15/167 (9%), PedvaxHIB: 20/166 (12%), p=0.36. Open-label study design would not affect immune response. Median time of post-dose 1 blood draw was similar between groups: Vaxelis 34 days (IQR 32–37 days) versus PedvaxHIB 34 days (IQR 31–39 days).

bImmunity is inferred from proportion with anti-Hib concentration above the putative correlate of short-term protection.

cAs modeled by constrained longitudinal data analysis, anti-Hib GMC 30 days post-dose 1 for Vaxelis group (0.41; 95% CI: 0.33–0.51) was non-inferior to that of the PedvaxHIB group (0.40; 95% CI: 0.31–0.50). Ratio of GMCs (Vaxelis:PedvaxHIB): 1.03 (95% CI: 0.75–1.41); the pre-specified non-inferiority criterion was met based on the lower bound of the 95% CI being >0.67.

dStudy was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian populations; WG members determined this did not warrant a downgrade.

eDowngraded because the absolute effect confidence interval is wide.

fSimilar loss to follow-up for anti-Hib IgG concentration 150 days post-dose 1: Vaxelis 39/167 (23%), PedvaxHIB 49/166 (30%), p=0.20. Open-label study design would not affect immune response. Median time of blood draw was similar between groups: Vaxelis 174 days (IQR 163–187 days) versus PedvaxHIB 180 days (IQR 162–189 days) post-dose 1.

gFrom the time of the first dose of study vaccine to the end of the last study visit (approximately 5 months).

hSimilar loss to follow-up through the last study visit: Vaxelis 21/166 (13%), PedvaxHIB 16/167 (10%), p=0.37. Open-label study design may bias reporting of serious adverse events but WG members determined this did not warrant a downgrade.

iIn the Vaxelis group 10 serious adverse events occurred among 9 participants. In the PedvaxHIB group, 15 serious adverse events occurred among 12 participants. The most common serious adverse event was acute respiratory infection 21/25 (84%). No serious adverse events were deemed related to study participation.

Table 5: Summary of Evidence for Outcomes of Interest

Outcome Importance Included in profile Certainty
Hib disease Important No NA
Post-dose 1 immunity Critical Yes Moderate
Post-primary series immunity Important Yes Moderate
Serious adverse events Critical Yes Moderate

NA = Not applicable

Appendices

Appendix 1. Studies Included in the Review of Evidence

Author, Year Study Design Setting Population Number of Participants Number Intervention
(Vaxelis)		 Number Comparison
(PedvaxHIB)		 Data Sources
Hammitt (NCT04978818),
2024		 RCT Anchorage, AK
Chinle, AZ
Fort Defiance, AZ
Gallup, NM
Shiprock, NM		 Healthy American Indian/Alaska Native infants born at gestational age ≥35 weeks, aged 42–90 days at the time of first study vaccination 333 166 167 Clinicaltrials.gov, ACIP presentations, ACIP Work Group presentations

Appendix 2: Search Strategies

Database Strategy Records*
Medline
(OVID)
1946-
  1. diphtheria-tetanus-acellular pertussis vaccines/
  2. diphtheria-tetanus-pertussis vaccine/
  3. Haemophilus Vaccines/
  4. (Vaxelis OR DTaP-IPV-Hib* OR DTaP5-IPV-Hib* OR DTaP-HB-IPV-Hib OR DTaP5-IPV-HB-Hib OR DTaP-HepB-IPV-Hib OR DTaP5-IPV-HepB-Hib OR DTPa-IPV-Hib* OR DTPa5-IPV-Hib* OR DTPa-HB-IPV-Hib OR DTPa5-IPV-HB-Hib OR DTPa-HepB-IPV-Hib or DTPa5-IPV-HepB-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR Hib PRP-OMP OR (Haemophilus influenza? type b ADJ3 vaccin*) OR (Hemophilus influenza? type b ADJ3 vaccin*) OR (H? Influenza? Type b ADJ3 Vaccin*) OR (Haemophilus influenza? type b ADJ3 conjugated) OR (Hemophilus influenzae type b ADJ3 conjugated) OR (H? influenza? type b ADJ3 conjugated) OR (Haemophilus influenza? type b ADJ3 immunization*) OR (Hemophilus influenza? type b ADJ3 immunization*) OR (H? influenza? type b ADJ3 immunization*) OR Hib vaccin* OR HibVax OR PedvaxHib OR Hib immunization* OR Hexavalent vaccin* OR NCT04978818).ti,ab,kf.
  5. 1-4/OR
  6. Immunogenicity, Vaccine/
  7. Vaccine Efficacy/
  8. exp "Drug-Related Side Effects and Adverse Reactions"/
  9. Ae.fs OR im.fs
  10. (Safe* OR immunogenicity OR antigenicity OR immune response OR adverse OR effective* OR efficacy OR tolerab*).ti,ab,kf.
  11. 6-10/OR
  12. 5 AND 11
  13. Limit 12 to yr="2014-current"
  14. Limit 13 to English language
 1249
Embase
(OVID)
1974-
  1. diphtheria pertussis poliomyelitis tetanus Haemophilus influenzae type b hepatitis B vaccine/
  2. exp Haemophilus influenzae type b vaccine/
  3. (Vaxelis OR DTaP-IPV-Hib* OR DTaP5-IPV-Hib* OR DTaP-HB-IPV-Hib OR DTaP5-IPV-HB-Hib OR DTaP-HepB-IPV-Hib OR DTaP5-IPV-HepB-Hib OR DTPa-IPV-Hib* OR DTPa5-IPV-Hib* OR DTPa-HB-IPV-Hib OR DTPa5-IPV-HB-Hib OR DTPa-HepB-IPV-Hib or DTPa5-IPV-HepB-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR Hib PRP-OMP OR (Haemophilus influenza? type b ADJ3 vaccin*) OR (Hemophilus influenza? type b ADJ3 vaccin*) OR (H? Influenza? Type b ADJ3 Vaccin*) OR (Haemophilus influenza? type b ADJ3 conjugated) OR (Hemophilus influenzae type b ADJ3 conjugated) OR (H? influenza? type b ADJ3 conjugated) OR (Haemophilus influenza? type b ADJ3 immunization*) OR (Hemophilus influenza? type b ADJ3 immunization*) OR (H? influenza? type b ADJ3 immunization*) OR Hib vaccin* OR HibVax OR PedvaxHib OR Hib immunization* OR Hexavalent vaccin* OR NCT04978818).ti,ab,kf.
  4. 1-3/OR
  5. Vaccine Immunogenicity/
  6. Vaccine Efficacy/
  7. exp Adverse drug reaction/
  8. Ae.fs
  9. (Safe* OR immunogenicity OR antigenicity OR immune response OR adverse OR effective* OR efficacy OR tolerab*).ti,ab,kf.
  10. 5-9/OR
  11. 4 AND 10
  12. Limit 11 to yr="2014-current"
  13. Limit 12 to English language
  14. Limit 13 to "pubmed/medline"
  15. 13 NOT 14

 

 1075

 
Cochrane Library
  1. [mh "diphtheria-tetanus-acellular pertussis vaccines"]
  2. [mh "diphtheria-tetanus-pertussis vaccine"]
  3. [mh "Haemophilus Vaccines"]
  4. (Vaxelis OR ("DTaP-IPV" NEXT Hib*) OR ("DTaP5-IPV" NEXT Hib*) OR "DTaP-HB-IPV-Hib" OR "DTaP5-IPV-HB-Hib" OR "DTaP-HepB-IPV-Hib" OR "DTaP5-IPV-HepB-Hib" OR ("DTPa-IPV" NEXT Hib*) OR ("DTPa5-IPV" NEXT Hib*) OR "DTPa-HB-IPV-Hib" OR "DTPa5-IPV-HB-Hib" OR "DTPa-HepB-IPV-Hib" OR "DTPa5-IPV-HepB-Hib" OR "DTaP-HBV-IPV-Hib" OR "DTaP5-IPV-HBV-Hib" OR "DTaP-HBV-IPV-Hib" OR "DTaP5-IPV-HBV-Hib" OR "Hib PRP-OMP" OR ((Haemophilus NEXT influenza? NEXT "type b") NEAR/3 vaccin*) OR ((Hemophilus NEXT influenza? NEXT "type b") NEAR/3 vaccin*) OR ((H? NEXT influenza? NEXT "type b") NEAR/3 vaccin*) OR ((Haemophilus NEXT influenza? NEXT "type b") NEAR/3 conjugated) OR ((Hemophilus NEXT influenza? NEXT "type b") NEAR/3 conjugated) OR ((H? NEXT influenza? NEXT "type b") NEAR/3 conjugated) OR ((Haemophilus NEXT influenza? NEXT "type b") NEAR/3 immunization*) OR ((Hemophilus NEXT influenza? NEXT "type b") NEAR/3 immunization*) OR ((H? NEXT influenza? NEXT "type b") NEAR/3 immunization*) OR Hib NEXT vaccin* OR HibVax OR PedvaxHib OR Hib NEXT immunization* OR Hexavalent NEXT vaccin* OR NCT04978818):ti,ab,kw
  5. #1 OR #2 OR #3 OR #4
  6. [mh "Immunogenicity, Vaccine"]
  7. [mh "Vaccine Efficacy"]
  8. [mh ^"Drug-Related Side Effects and Adverse Reactions"]
  9. (Safe* OR immunogenicity OR antigenicity OR "immune response" OR adverse OR effective* OR efficacy OR tolerab*):ti,ab,kw
  10. #6 OR #7 OR #8 OR #9
  11. #5 AND #10

with Cochrane Library publication date from Jan 2014 to Apr 2024

 544

 
CINAHL
(EBSCOHost)
  1. (MH "Diphtheria-Tetanus-acellular Pertussis Vaccines")
  2. (MH "Diphtheria-Tetanus-Pertussis Vaccine")
  3. (MH "HIB Vaccine")
  4. (Vaxelis OR DTaP-IPV-Hib* OR DTaP5-IPV-Hib* OR DTaP-HB-IPV-Hib OR DTaP5-IPV-HB-Hib OR DTaP-HepB-IPV-Hib OR DTaP5-IPV-HepB-Hib OR DTPa-IPV-Hib* OR DTPa5-IPV-Hib* OR DTPa-HB-IPV-Hib OR DTPa5-IPV-HB-Hib OR DTPa-HepB-IPV-Hib or DTPa5-IPV-HepB-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR "Hib PRP-OMP" OR ("Haemophilus influenzae type b" N3 vaccin*) OR ("Hemophilus influenzae type b" N3 vaccin*) OR ("H. Influenzae Type b" N3 Vaccin*) OR ("Haemophilus influenzae type b" N3 conjugated) OR ("Hemophilus influenzae type b" N3 conjugated) OR ("H. influenzae type b" N3 conjugated) OR ("Haemophilus influenzae type b" N3 immunization*) OR ("Hemophilus influenzae type b" N3 immunization*) OR ("H. influenzae type b" N3 immunization*) OR OR ("Haemophilus influenza type b" N3 vaccin*) OR ("Hemophilus influenza type b" N3 vaccin*) OR ("H. Influenza Type b" N3 Vaccin*) OR ("Haemophilus influenza type b" N3 conjugated) OR ("Hemophilus influenza type b" N3 conjugated) OR ("H. influenza type b" N3 conjugated) OR ("Haemophilus influenza type b" N3 immunization*) OR ("Hemophilus influenza type b" N3 immunization*) OR ("H. influenza type b" N3 immunization*) OR "Hib vaccin*" OR HibVax OR PedvaxHib OR "Hib immunization*" OR "Hexavalent vaccin*" OR NCT04978818)
  5. S1-S4/OR
  6. (MH "Immunogenicity, Vaccine")
  7. (MH "Vaccine Efficacy")
  8. (Safe* OR immunogenicity OR antigenicity OR "immune response" OR adverse OR effective* OR efficacy OR tolerab*)
  9. S6-S9/OR
  10. S5 AND S10

Limiters - Publication Date: 20140101-20241231; English Language; Exclude MEDLINE records

 112

 
Scopus (INDEXTERMS("diphtheria-tetanus-acellular pertussis vaccines") OR INDEXTERMS("diphtheria-tetanus-pertussis vaccine") OR INDEXTERMS("Haemophilus Vaccines") OR TITLE-ABS-KEY(Vaxelis OR DTaP-IPV-Hib* OR DTaP5-IPV-Hib* OR DTaP-HB-IPV-Hib OR DTaP5-IPV-HB-Hib OR DTaP-HepB-IPV-Hib OR DTaP5-IPV-HepB-Hib OR DTPa-IPV-Hib* OR DTPa5-IPV-Hib* OR DTPa-HB-IPV-Hib OR DTPa5-IPV-HB-Hib OR DTPa-HepB-IPV-Hib or DTPa5-IPV-HepB-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR "Hib PRP-OMP" OR ("Haemophilus influenza? type b" W/3 vaccin*) OR ("Hemophilus influenza? type b" W/3 vaccin*) OR ("H? Influenza? Type b" W/3 Vaccin*) OR ("Haemophilus influenza? type b" W/3 conjugated) OR ("Hemophilus influenzae type b" W/3 conjugated) OR ("H? influenza? type b" W/3 conjugated) OR ("Haemophilus influenza? type b" W/3 immunization*) OR ("Hemophilus influenza? type b" W/3 immunization*) OR ("H? influenza? type b" W/3 immunization*) OR "Hib vaccin*" OR HibVax OR PedvaxHib OR "Hib immunization*" OR "Hexavalent vaccin*" OR NCT04978818)) AND (INDEXTERMS("Immunogenicity, Vaccine") OR INDEXTERMS("Vaccine Efficacy") OR INDEXTERMS("Drug-Related Side Effects and Adverse Reactions") OR TITLE-ABS-KEY(Safe* OR immunogenicity OR antigenicity OR "immune response" OR adverse OR effective* OR efficacy OR tolerab*)) AND NOT INDEX(medline)
Limit to yr="2014-current"		 250
Clinicaltrials.gov diphtheria-tetanus-acellular pertussis vaccine OR diphtheria-tetanus-pertussis vaccine OR Haemophilus Vaccines OR Hemophilus Vaccines OR Vaxelis OR DTaP-IPV-Hib* OR DTaP5-IPV-Hib* OR DTaP-HB-IPV-Hib OR DTaP5-IPV-HB-Hib OR DTaP-HepB-IPV-Hib OR DTaP5-IPV-HepB-Hib OR DTPa-IPV-Hib* OR DTPa5-IPV-Hib* OR DTPa-HB-IPV-Hib OR DTPa5-IPV-HB-Hib OR DTPa-HepB-IPV-Hib or DTPa5-IPV-HepB-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR DTaP-HBV-IPV-Hib OR DTaP5-IPV-HBV-Hib OR Hib PRP-OMP OR Haemophilus influenzae type b vaccin* OR Hemophilus influenzae type b vaccin* OR H. Influenzae Type b vaccin* OR Haemophilus influenzae type b conjugated OR Hemophilus influenzae type b conjugated OR H. influenzae type b conjugated OR Haemophilus influenzae type b immunization* OR Hemophilus influenzae type b immunization* OR H. influenzae type b immunization* OR Hib vaccin* OR HibVax OR PedvaxHib OR Hib immunization* OR Hexavalent vaccin* 128

 

*Search was conducted on April 29, 2024. A total of 2,332 de-duplicated records published from 2014 to present were screened for inclusion in the GRADE evidence profile.

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Content Source:
National Center for Immunization and Respiratory Diseases (NCIRD)
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  2. Oliver SE, Moore KL. Licensure of a Diphtheria and Tetanus Toxoids and Acellular Pertussis, Inactivated Poliovirus, Haemophilus influenzae Type b Conjugate, and Hepatitis B Vaccine and Guidance for Use in Infants. MMWR Morb Mortal Wkly Rep 2020;69:136–9.
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