Benefits of the intervention
Serogrouping is not a relevant concept for diphtheria, tetanus, pertussis, or hepatitis B in the context of vaccine coverage
There are 6 serotypes of Haemophilus influenzae (a to f) of which type b was the commonest cause of severe disease in children. Disease due to other serotypes and non-typeable Haemophilus influenzae can cause disease. Go to footnote 1, Go to footnote 2, Go to footnote 3, Go to footnote 4, Go to footnote 5
Poliovirus exists in three distinct serotypes: types 1, 2, and 3. Immunity to one serotype does not confer protection against the others, necessitating vaccines that target all three (trivalent vaccine). All the available Hexavalent vaccines contains all the three Polio serotypes. Go to footnote 6, Go to footnote 7
Clinical studies consistently show that hexavalent vaccines are highly effective in generating protective immune responses against all six targeted diseasesGo to footnote 3, Go to footnote 8, Go to footnote 9, Go to footnote 10, Go to footnote 11, Go to footnote 12, Go to footnote 13, Go to footnote 14, Go to footnote 15 :
- Diphtheria - Nearly all children achieve seroprotective antibody levels after vaccination and booster doses with non-inferior protection compared to monovalent or pentavalent vaccines. Go to footnote 9
- Tetanus - 100% seroprotection rates reported post-booster; strong and persistent antibody responses with no evidence of reduced efficacy compared to monovalent or other combination vaccines. Go to footnote 9
- Pertussis - High seroconversion rates (94–95% for Bordetella pertussis, 77–87% for pertussis toxin). Head-to-head studies and clinical trials confirm that the immune response to pertussis antigens in hexavalent vaccines is non-inferior to that of other licensed combination vaccines, including pentavalent and monovalent formulations. Some differences in antibody levels (e.g., anti-pertussis toxin, anti-pertactin) exist, but these have not shown clear clinical relevance. Hexavalent vaccines may contain either whole cell pertussis (wP) or acellular pertussis (aP) antigens, which influence immunogenicity and reactogenicity profiles, with aP generally associated with lower reactogenicity. Go to footnote 15
- Hepatitis B - >99% seroprotection post-booster with no significant reduction compared to the monovalent vaccine. Go to footnote 12
- Hib - 96–100% achieve protective antibody levels post-primary and booster doses. There is some evidence that Hib conjugate vaccine in combination with acellular pertussis (DTaP-Hib) induces a lower antibody response than Hib conjugate in combination with whole cell pertussis (DTwP-Hib) or separately administered DTaP and Hib conjugate vaccines. Go to footnote 14
- Poliomyelitis - 98–100% seroprotection for all three poliovirus types post-booster. Non inferiority (as measures by antibody titers) has been demonstrated for wP containing Hexavalent and IPV/OPV. Go to footnote 10, Go to footnote 11, Go to footnote 13
The duration of protection varies by disease component, but evidence shows that these vaccines provide strong initial immunity and long-lasting immune memory, especially when booster doses are included . Go to footnote 16, Go to footnote 17, Go to footnote 18, Go to footnote 19, Go to footnote 5, Go to footnote 6, Go to footnote 20, Go to footnote 21, Go to footnote 22, Go to footnote 23, Go to footnote 24, Go to footnote 25, Go to footnote 26, Go to footnote 27 .
Diphtheria - Data on the duration of seroprotection from 2 large representative population studies from the Netherlands, using a complete 3-dose primary series plus 3-dose booster series prior to adolescence, indicate that this schedule results in very high seroprevalence above the threshold for basic protection (≥0.01 IU/mL) up to 39 years of age and potentially longer. Go to footnote 16, Go to footnote 22, Go to footnote 25
Tetanus - Data from serological studies suggest that a primary series of 3 TTCV doses in infancy plus a booster during the second year of life will provide 3–5 years of protection. A further booster dose (e.g. in early childhood) provides protection into adolescence, and another booster during adolescence induces immunity that lasts through much of adulthood, providing protection to women of reproductive age. Go to footnote 17, Go to footnote 21, Go to footnote 25
Pertussis - Whereas little is known about the duration of protection following pertussis vaccination in LMICs countries, several studies in HICs show that protection wanes after 4-12 years. Go to footnote 18, Go to footnote 20
Hepatitis B - In a study in Alaska, USA, a 3-dose vaccination schedule prevented all clinically appparent and chronic HepB infection for at least 30 years. Go to footnote 19, Go to footnote 23, Go to footnote 24, Go to footnote 26
Hib - Although there is some evidence of a decrease over time in the proportion of Hib vaccine recipients with antibody levels higher than the set thresholds, there is only limited evidence to suggest that this decline is associated with an increase in clinical disease. Go to footnote 5, Go to footnote 25
Poliomyelitis - The exact duration of immunity following a complete IPV series is not fully determined; however, it is believed to confer protection for many years. Go to footnote 6
- Go back to footnote reference 1
Shuel M, Hoang L, Law DKS, Tsang R (2011). Invasive Haemophilus influenzae in British Columbia: non-Hib and non-typeable strains causing disease in children and adults. Int J Infect Dis. 15:e167–e173. doi:10.1016/j.ijid.2010.10.005.
- Go back to footnote reference 2
Knuf M et al. (2021). Hexavalent vaccines: what can we learn from head-to-head studies? Vaccine. 39(41):6025–6036. doi:10.1016/j.vaccine.2021.08.086.
- Go back to footnote reference 3aGo back to footnote reference 3b
Boisnard F, Manson C, Serradell L, Macina D (2023). DTaP-IPV-HB-Hib vaccine (Hexaxim): an update 10 years after first licensure. Expert Rev Vaccines. 22:1196–1213. doi:10.1080/14760584.2023.2280236.
- Go back to footnote reference 4
Vesikari T, Borrow R, Da Costa X, Richard P, Eymin C, Boisnard F, Lockhart S (2017). Concomitant administration of a fully liquid, ready-to-use DTaP-IPV-HB-PRP-T hexavalent vaccine with a meningococcal serogroup C conjugate vaccine in infants. Vaccine. 35(3):452–458. doi:10.1016/j.vaccine.2016.11.053.
- Go back to footnote reference 5aGo back to footnote reference 5bGo back to footnote reference 5c
Haemophilus influenzae type b (Hib) vaccine: WHO position paper, July 2013. Weekly Epidemiological Record. 2013; 88(39): 413–426.
- Go back to footnote reference 6aGo back to footnote reference 6bGo back to footnote reference 6c
Polio vaccines: WHO position paper, June 2022. Weekly Epidemiological Record. 2022; 97(25): 277–296.7.
- Go back to footnote reference 7
Centers for Disease Control and Prevention (CDC) (no date). Polio vaccines [website]. Atlanta: CDC. Available at: https://www.cdc.gov/polio/vaccines/index.html (accessed 24 June 2025).
- Go back to footnote reference 8
Dakin A, Borrow R, Arkwright P (2022). A review of the DTaP-IPV-HB-PRP-T Hexavalent vaccine in pediatric patients. Expert Rev Vaccines. 22:104–117. doi:10.1080/14760584.2023.2161519.
- Go back to footnote reference 9aGo back to footnote reference 9bGo back to footnote reference 9c
Wanlapakorn N, Sarawanangkoor N, Srimuan D, Thatsanathorn T, Thongmee T, et al. (2024). Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines. Hum Vaccin Immunother. 20. doi:10.1080/21645515.2024.2352909.
- Go back to footnote reference 10aGo back to footnote reference 10b
Knuf M, Haas H, García-Corbeira P, Turriani E, Mukherjee P, et al. (2021). Hexavalent vaccines: what can we learn from head-to-head studies? Vaccine. doi:10.1016/j.vaccine.2021.08.086.
- Go back to footnote reference 11aGo back to footnote reference 11b
Sharma H, Parekh S, Pujari P, Shewale S, Desai S, et al. (2024). A randomized, active-controlled, multi-centric, phase-II clinical study to assess safety and immunogenicity of a fully liquid DTwP-HepB-IPV-Hib hexavalent vaccine (HEXASIIL®) in Indian toddlers. Vaccine. 42(26):126380. doi:10.1016/j.vaccine.2024.126380.
- Go back to footnote reference 12aGo back to footnote reference 12b
Steiner M, Ramakrishnan G, Gartner B, Van Der Meeren O, Jacquet J, et al. (2010). Lasting immune memory against hepatitis B in children after primary immunization with 4 doses of DTPa-HBV-IPV/Hib in the first and 2nd year of life. BMC Infect Dis. 10:9. doi:10.1186/1471-2334-10-9.
- Go back to footnote reference 13aGo back to footnote reference 13b
Sanchez L, Rungmaitree S, Kosalaraksa P, Jantarabenjakul W, Leclercq J, Yaiprayoon Y, Midde VJ, Varghese K, Mangarule S, Noriega F (2023). Immunogenicity and safety of a hexavalent DTwP-IPV-HB-PRPT vaccine versus separate DTwP-HB-PRPT, bOPV, and IPV vaccines administered at 2, 4, 6 months of age concomitantly with rotavirus and pneumococcal conjugate vaccines in healthy infants in Thailand. Pediatr Infect Dis J. 42(8):711–718. doi:10.1097/INF.0000000000003975.
- Go back to footnote reference 14aGo back to footnote reference 14b
Haemophilus influenzae type b (Hib) vaccine: WHO position paper, July 2013. Weekly Epidemiological Record. 2013;88(39):413–426.
- Go back to footnote reference 15aGo back to footnote reference 15b
Patterson J, Kagina BM, Gold M, Hussey GD, Muloiwa R (2018). Comparison of adverse events following immunisation with acellular and whole-cell pertussis vaccines: a systematic review. Vaccine. 36:6007–6016. doi:10.1016/j.vaccine.2018.08.022.
- Go back to footnote reference 16aGo back to footnote reference 16b
Diphtheria vaccine: WHO position paper, August 2017. Weekly Epidemiological Record. 2017; 92(31): 417–435.
- Go back to footnote reference 17aGo back to footnote reference 17b
Tetanus vaccine: WHO position paper, February 2017. Weekly Epidemiological Record. 2017; 92(6): 53–76.
- Go back to footnote reference 18aGo back to footnote reference 18b
Pertussis vaccine: WHO position paper, August 2015. Weekly Epidemiological Record. 2015; 90(35): 433–460.
- Go back to footnote reference 19aGo back to footnote reference 19b
Hepatitis B vaccines: WHO position paper, July 2017. Weekly Epidemiological Record. 2017; 92(27): 369–392.
- Go back to footnote reference 20aGo back to footnote reference 20b
Wendelboe, A.M., et al. (2005) ‘Duration of immunity against pertussis after natural infection or vaccination’, Pediatric Infectious Disease Journal, 24(Suppl. 5), pp. S58–S61.
- Go back to footnote reference 21aGo back to footnote reference 21b
Borrow, R., Balmer, P. and Roper, M.H. (2007) The immunologic basis for immunization: module 3: tetanus. Geneva: World Health Organization. Available at: http://apps.who.int/iris/bitstream/10665/43687/1/9789241595551_eng.pdf (accessed 30 June 2025).
- Go back to footnote reference 22aGo back to footnote reference 22b
Swart, E.M., et al. (2016) ‘Long-term protection against diphtheria in the Netherlands after 50 years of vaccination: results from a seroepidemiological study’, PLoS ONE, 11(2), e0148605. doi: 10.1371/journal.pone.0148605.
- Go back to footnote reference 23aGo back to footnote reference 23b
Bruce, M.G., et al. (2016) ‘Antibody levels and protection after hepatitis B vaccine: results of a 30-year follow-up study and response to a booster dose’, Journal of Infectious Diseases, 214, pp. 16–22. doi: 10.1093/infdis/jiw144.
- Go back to footnote reference 24aGo back to footnote reference 24b
Wanlapakorn, N., Sarawanangkoor, N., Srimuan, D., Thatsanathorn, T., Klinfueng, S. and Poovorawan, Y. (2024) ‘Persistence of hepatitis B surface antibody until 7 years of age following administration of hexavalent and pentavalent vaccines in children at 2, 4, 6, and 18 months’, Vaccine: X, 20. doi: 10.1016/j.jvacx.2024.100561.
- Go back to footnote reference 25aGo back to footnote reference 25bGo back to footnote reference 25cGo back to footnote reference 25d
Wanlapakorn, N., Sarawanangkoor, N., Srimuan, D., Thatsanathorn, T., Thongmee, T. and Poovorawan, Y. (2024) ‘Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines’, Human Vaccines & Immunotherapeutics, 20. doi: 10.1080/21645515.2024.2352909.
- Go back to footnote reference 26aGo back to footnote reference 26b
Avdičová, M., Crasta, P., Hardt, K. and Kovac, M. (2015) ‘Lasting immune memory against hepatitis B following challenge 10-11 years after primary vaccination with either three doses of hexavalent DTPa-HBV-IPV/Hib or monovalent hepatitis B vaccine at 3, 5 and 11-12 months of age’, Vaccine, 33(23), pp. 2727–2733. doi: 10.1016/j.vaccine.2014.06.070.
- Go back to footnote reference 27
Mangarule, S., Sapru, A., Bavdekar, A., Kawade, A., Lalwani, S., et al. (2023) ‘Antibody persistence following administration of a hexavalent DTwP-IPV-HB-PRPT vaccine versus separate DTwP-HB-PRPT and IPV vaccines and safety and immunogenicity of a booster dose of DTwP-IPV-HB-PRP~T administered with an MMR vaccine in healthy infants in India’, Pediatric Infectious Disease Journal, 42(12), pp. 1128–1135.
