A review of the DTaP-IPV-HB-PRP-T Hexavalent vaccine in pediatric patients

Figures & data

Figure 1. Flowchart of the literature included in the systematic review.

Table 1. Clinical trial characteristics comparing the immunogenicity and safety of primary and booster DT2aP-IPV-Hib-HBV with comparator vaccines.

Trial Number	Country	Schedule	Comparator Vaccine	Number of subjects	Co-vaccination	Noninferior Immunogenicity	Comparable Safety Profile	Reference
NCT00362336	South Africa	6, 10, 14 w	Combact-Hib, Engerix B Pediatric, OPV	715	N/A	Yes	Yes	[33]
NCT00831311	Argentina	2, 4, 6 m	Pentaxim, Engerix B Pediatric	624	N/A	Yes	Yes	[34]
NCT00303316	Argentina	18 m*	Pentaxim, Engerix B Pediatric	458	N/A	Yes – Hep B antibody persistence lower in DT2aP-IPV-Hib-HBV group prior to booster	Yes – 1 case of nonfebrile convulsions in DT2aP-IPV-Hib-HBV group	[35]
NCT00404651	Mexico	2, 4, 6 m	DT3aP-IPV-Hib-HBV	1189	N/A	Yes	Yes	[36]
NCT00654901	Mexico	18 m**	DT3aP-IPV-Hib-HBV	1189	N/A	Yes	Yes	[36]
U1111-1122–2235	Sweden, Finland	3, 5, 11–12 m	DT3aP-IPV-Hib-HBV	546	PCV13	Yes	Yes	[37]
NCT02094833	Korea	2, 4, 6 m	Pentaxim, Euvax B	310	Euvax B^	Yes	Yes – higher incidence of pyrexia in DT2aP-IPV-Hib-HBV group	[38]
NCT00315055	Turkey	2, 3, 4 m	Pentaxim, Engerix B Pediatric	310	N/A	Yes	Yes – higher incidence of fever (non-grade 3) in DT2aP-IPV-Hib-HBV group	[39]
NCT00619502	Turkey	15–18 m***	Pentaxim, Engerix B Pediatric	310	N/A	Yes – Hep B antibody persistence lower in DT2aP-IPV-Hib-HBV group prior to booster	Yes – higher incidence of fever (non-grade 3) in DT2aP-IPV-Hib-HBV group	[39]
NCT01177722	Colombia, Costa Rica	2, 4, 6 m	DT3aP-IPV-Hib-HBV	1376	PCV7, Rotarix	Yes	Yes – higher incidence of erythema and overall grade 3 reactions in DT2aP-IPV-Hib-HBV group	[40]
NCT01444781	Colombia, Costa Rica	12–24 m	DT3aP-IPV-Hib-HBV	1376	PCV7, Rotarix	Yes	Yes	[40]
NCT00401531	Thailand	2, 4, 6 m	DT3aP-IPV-Hib-HBV	412	PCV7, Euvax B	Yes	Yes	[41]
U1111-1122–2329	Germany, Czech Republic	2, 3, 4 m	DT3aP-IPV-Hib-HBV	529	PCV13, RotaTeq	Yes	Yes – 1 case of convulsions in DT2aP-IPV-Hib-HBV group	[42]
U1111-1122–2362	Germany, Czech Republic	11–15 m	DT3aP-IPV-Hib-HBV	529	PCV13^	Yes – Hep B antibody persistence lower and PRP antibody persistence higher in Hexaxim group prior to booster	Yes	[42]
NCT00362336	South Africa	18–19 m	Combact-Hib, Engerix B Pediatric, OPV	567	Trimovax, Varilrix, Rouvax	Yes	Yes	[43]
NCT00313911	Peru, Mexico	2, 4, 6 m	Tritanrix-Hep B, Hiberix, OPV	2133	N/A	Yes	Yes – 1 case of hypotonic-hyporesponsive episode in the Hexaxim group	[44]
NCT00831753	Peru	2, 4, 6 m	DT3aP-IPV-Hib-HBV	263	N/A	Yes	Yes	[45]

*Primary schedule from NCT00831311 [34], all subjects given comparator vaccine booster at 18 months. **Primary schedule from NCT00404651 (36), all subjects given investigational vaccine booster at 18 months. ***Primary schedule from NCT00315055 (39), all subjects given investigational vaccine booster at 15–18 months. PCV = Pneumococcal Conjugate Vaccine. ^Euvax B only given at 1 + 6 months in Pentaxim group and at birth in DT2aP-IPV-Hib-HBV group. m = months. w = weeks. OPV = Oral Polio Virus. Hib = Haemophilus influenzae type b. HepB = Hepatitis B.

Table 2. Immune response of DT2aP-IPV-Hib-HBV vs DT3aP-IPV-Hib-HBVfor each antigen post primary or booster vaccination.

Antigen	Response Criteria	Vaccine Response Range (%)
		DT2aP-IPV-Hib-HBV	DT3aP-IPV-Hib-HBV
Diphtheria Toxoid	≥0.01 IU/mL	96–100	99–100
	≥0.1 IU/mL	62–100	56–100
Tetanus Toxoid	≥0.01 IU/mL	100	100
	≥0.1 IU/mL	86–100	87–100
Polio 1	≥1/8 dilution	100	100
Polio 2	≥1/8 dilution	100	100
Polio 3	≥1/8 dilution	100	100
Hepatitis B	≥10mIU/mL	96–100	99–100
	≥100mIU/mL	72–99	87–100
Haemophilus B Conjugate	≥0.15 µg/ml	91–100	86–100
Pertussis Toxoid	≥4-fold increase	79–97	80–96
Filamentous Hemagglutinin	≥4-fold increase	60–98	76–97

IU/mL = International Units per milliliter. Data derived from references 36–38, 40–42, 45

Table 3. Clinical trial characteristics of studies without comparator vaccines.

Trial Number	Country	Schedule	Subjects	Covaccination	Aim of Study	Acceptable Immune Response?	Acceptable Safety Profile?	Main Conclusion	Reference
NCT01839175	Finland	2, 3, 4 m*	354	PCV13, RotaTeq	Evaluate immunogenicity and safety of DT2aP-IPV-Hib-HBVwith or without NeisVac-C covaccination	Yes	Yes – crying and vomiting more frequent without NeisVac-C. 1 case of fever ≤39.5°C in group without NeisVac-C	Immunogenicity of each vaccine not affected by coadministration, and safety profile remains similar.	[46]
2012–005547-24	Finland	12–13 m**	312	PCV13, M-M-RvaxPro	Evaluate immunogenicity and safety of DT2aP-IPV-Hib-HBVwith or without MenACWY-TT covaccination	Yes	Yes – reactogenicity was higher with coadministration of MenACWY -TT but still acceptable	Concomitant vaccination with DT2aP-IPV-Hib-HBV and MenACWY-TT is supported.	[47]
NCT01948193	India	6, 10, 14 w	177	Hep B, OPV***	Evaluate the immunogenicity and safety of DT2aP-IPV-Hib-HBV (single arm)	Yes	Yes	DT2aP-IPV-Hib-HBV is highly immunogenic and safe for use in infants.	[48]
U1111-1122–2329	Spain	2, 4, 6 m	236	PCV13, RotaTeq, NeisVac-C^	Evaluation of a Hexavalent-Pentavalent-Hexavalent vaccine schedule with DT2aP-IPV-Hib-HBV at 2, 6 months and Pentaxim at 4 months	Yes	Yes	Hexavalent-Pentavalent-Hexavalent vaccine schedules are immunogenic and safe.	[49]
U1111-1122–2362	Spain	18 m****	189	PCV13	Evaluation of a Pentaxim booster following a Hexavalent-Pentavalent-Hexavalent vaccine schedule with DT2aP-IPV-Hib-HBV at 2, 6 months and Pentaxim at 4 months	Yes	Yes	Hexavalent-Pentavalent-Hexavalent vaccine schedules are immunogenic and safe.	[49]
NCT02817451	South Africa	6, 10, 14 w, 15–18 m	64	OPV, BCG, PCV13 and rotavirus^^	Evaluation of immunogenicity and safety of DT2aP-IPV-Hib-HBV in HIV-exposed infected individuals	Yes	Yes	DT2aP-IPV-Hib-HBV is immunogenic and safe in HIV-exposed infected individuals	[50]
NCT02428491	Vietnam	2, 3, 4, 16–17 m	354	N/A	Evaluation of immunogenicity and safety of DT2aP-IPV-Hib-HBV in infants who received a Hep B vaccine at birth	Yes	Yes	DT2aP-IPV-Hib-HBV is immunogenic and safe in infants who receive a Hep B vaccine at birth	[51]
U1111-1143-8252	Poland, Russia	Poland: Day 0, 45, 90. Russia: 6 m	Poland: 50. Russia: 100	N/A	Evaluation of immunogenicity and safety of DT2aP-IPV-Hib-HBV (single arm) in Poland and DT2aP-IPV-Hib-HBV after 2 doses of Pentaxim with Hep B	Yes	Yes	DT2aP-IPV-Hib-HBV is immunogenic and safe in infants when given in 3 doses or as a last dose after 2 doses of Pentaxim with Hep B	[52]

*2 and 4 months only for NeisVac-C®. **Primary schedule from NCT01839175 (46). ***Hepatitis B and OPV vaccination at birth only. ****Primary schedule from U1111-1122–2329 (49). ^PCV13 at 2, 4, and sometimes 6 months, RotaTeq at 2, 4, 6 months, NeisVac-C at 2 months. ^^OPV and BCG (Bacillus Calmett-Guérin) at birth, pneumococcal at 6, 14 weeks and 9 months, rotavirus at 6, 13 weeks. BCG = Bacillus Calmett-Guérin. OPV = Oral Polio Virus. PCV = Pneumococcal Conjugate Vaccine. HepB = Hepatitis B m = months. w = weeks.

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