Safety, reactogenicity and immunogenicity of a booster dose of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Malian children

Alassane Dicko, Gaoussou Santara, Almahamoudou Mahamar, Youssoufa Sidibe, Amadou Barry, Yahia Dicko, Aminata Diallo, Amagana Dolo, Ogobara Doumbo, Fakrudeen Shafi, Nancy François, Ana Strezova, Dorota Borys, Lode Schuerman, Alassane Dicko, Gaoussou Santara, Almahamoudou Mahamar, Youssoufa Sidibe, Amadou Barry, Yahia Dicko, Aminata Diallo, Amagana Dolo, Ogobara Doumbo, Fakrudeen Shafi, Nancy François, Ana Strezova, Dorota Borys, Lode Schuerman

Abstract

Background: Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was previously shown to be immunogenic and well tolerated in Malian children. Data on booster vaccination with a fourth consecutive dose of PHiD-CV are available for Europe, Asia and Latin America but are lacking for Africa. The present study evaluated further the safety, reactogenicity and immunogenicity of a fourth consecutive (booster) dose of PHiD-CV.

Results: Low incidences of AEs with grade 3 intensity (2.1% of subjects) were observed. There were no reports of large swelling reactions and serious adverse events. One month post-booster vaccination, for each vaccine pneumococcal serotype, at least 97.8% of subjects had antibody concentrations ≥ 0.2 μg/ml, and at least 97.1% of subjects had opsonophagocytic activity ≥ 8. From pre- to post-booster, a 12.3-fold increase in anti-protein D geometric mean concentration was observed.

Methods: This phase III, open-label study was conducted in Ouelessebougou, Mali, between November 2009 and June 2010. The study population consisted of Malian children previously primed (3 doses) with PHiD-CV in study NCT00678301 receiving a fourth consecutive (booster) dose of PHiD-CV in the second year of life. The incidences of adverse events (AEs) with grade 3 intensity (primary objective) or of any intensity (secondary objective), and the immunogenicity (secondary objective) of the PHiD-CV booster dose were assessed.

Conclusion: A booster dose of PHiD-CV was well tolerated when administered to Malian children in the second year of life and was highly immunogenic for all 10 vaccine pneumococcal serotypes and NTHi protein D. (ClinicalTrials.gov identifier: NCT00985465).

Keywords: Mali; PHiD-CV; antibody persistence; booster; immunogenicity; pneumococcal conjugate vaccine; reactogenicity; safety.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3859761/bin/hvi-9-382-g2.jpg
Figure 2. Kinetics of serotype-specific OPA geometric mean titres (GMTs) for vaccine pneumococcal serotypes and cross-reactive serotypes 6A and 19A, post-primary, pre-booster and post-booster vaccination with PHiD-CV (ATP immunogenicity cohort). ATP, according-to-protocol; OPA , opsonophagocytic activity; GMT, geometric mean titre.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/3859761/bin/hvi-9-382-g1.jpg
Figure 1. Kinetics of serotype-specific antibody geometric mean concentrations (GMCs, GSK’s 22F-inhibition ELISA) for vaccine pneumococcal serotypes and cross-reactive serotypes 6A and 19A, post-primary, pre-booster and post-booster vaccination with PHiD-CV (ATP immunogenicity cohort). GMC, geometric mean concentration; ATP, according-to-protocol; GSK’s 22F-ELISA, GlaxoSmithKline’s 22F-inhibition enzymelinked immunosorbent assay. Note: Immunogenicity results related to one month post- primary were derived from the primary vaccination study NCT00678301 by re-calculation based on the ATP immunogenicity cohort of the booster study.

References

    1. Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, et al. Child Health Epidemiology Reference Group of WHO and UNICEF Global, regional, and national causes of child mortality in 2008: a systematic analysis. Lancet. 2010;375:1969–87. doi: 10.1016/S0140-6736(10)60549-1.
    1. Global Alliance for Vaccines and Immunization (GAVI): Advance Market Commitments for Vaccines Update: World's Poorest Children Among First to Receive New Life-Saving Pneumococcal Vaccines. 2010 []
    1. Hausdorff WP, Feikin DR, Klugman KP. Epidemiological differences among pneumococcal serotypes. Lancet Infect Dis. 2005;5:83–93.
    1. Johnson HL, Deloria-Knoll M, Levine OS, Stoszek SK, Hance LF, Reithinger R, et al. Systemic evaluation of serotypes causing invasive pneumococcal disease among children under five: the global serotype project. PLoS Med. 2010;7:10. doi: 10.1371/journal.pmed.1000348.
    1. World Health Organization (WHO) Pneumococcal conjugate vaccine for childhood immunization--WHO position paper. Wkly Epidemiol Rec. 2007;82:93–104.
    1. Saaka M, Okoko BJ, Kohberger RC, Jaffar S, Enwere G, Biney EE, et al. Immunogenicity and serotype-specific efficacy of a 9-valent pneumococcal conjugate vaccine (PCV-9) determined during an efficacy trial in The Gambia. Vaccine. 2008;26:3719–26. doi: 10.1016/j.vaccine.2008.04.066.
    1. Klugman KP, Madhi SA, Adegbola RA, Cutts F, Greenwood B, Hausdorff WP. Timing of serotype 1 pneumococcal disease suggests the need for evaluation of a booster dose. Vaccine. 2011;29:3372–3. doi: 10.1016/j.vaccine.2011.02.089.
    1. Liñares J, Ardanuy C, Pallares R, Fenoll A. Changes in antimicrobial resistance, serotypes and genotypes in Streptococcus pneumoniae over a 30-year period. Clin Microbiol Infect. 2010;16:402–10. doi: 10.1111/j.1469-0691.2010.03182.x.
    1. Whitney CG, Pilishvili T, Farley MM, Schaffner W, Craig AS, Lynfield R, et al. Effectiveness of seven-valent pneumococcal conjugate vaccine against invasive pneumococcal disease: a matched case-control study. Lancet. 2006;368:1495–502. doi: 10.1016/S0140-6736(06)69637-2.
    1. Dicko A, Odusanya OO, Diallo AI, Santara G, Barry A, Dolo A, et al. Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in infants in Mali and Nigeria: a randomized controlled trial. BMC Public Health. 2011;11:882–93. doi: 10.1186/1471-2458-11-882.
    1. Chevallier B, Vesikari T, Brzostek J, Knuf M, Bermal N, Aristegui J, et al. Safety and reactogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with routine childhood vaccines. Pediatr Infect Dis J. 2009;28(Suppl):S109–18. doi: 10.1097/INF.0b013e318199f62d.
    1. Wysocki J, Tejedor JC, Grunert D, Konior R, Garcia-Sicilia J, Knuf M, et al. Immunogenicity of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when coadministered with different neisseria meningitidis serogroup C conjugate vaccines. Pediatr Infect Dis J. 2009;28(Suppl):S77–88. doi: 10.1097/INF.0b013e318199f609.
    1. Knuf M, Szenborn L, Moro M, Petit C, Bermal N, Bernard L, et al. Immunogenicity of routinely used childhood vaccines when coadministered with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) Pediatr Infect Dis J. 2009;28(Suppl):S97–108. doi: 10.1097/INF.0b013e318199f61b.
    1. Silfverdal SA, Hogh B, Bergsaker MR, Skerlikova H, Lommel P, Borys D, et al. Immunogenicity of a 2-dose priming and booster vaccination with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine. Pediatr Infect Dis J. 2009;28:e276–82. doi: 10.1097/INF.0b013e3181b48ca3.
    1. Prymula R, Siegrist CA, Chlibek R, Zemlickova H, Vackova M, Smetana J, et al. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials. Lancet. 2009;374:1339–50. doi: 10.1016/S0140-6736(09)61208-3.
    1. Vesikari T, Karvonen A, Lindblad N, Korhonen T, Lommel P, Willems P, et al. Safety and immunogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine coadministered with measles-mumps-rubella-varicella vaccine in children aged 12 to 16 months. Pediatr Infect Dis J. 2010;29:e47–56. doi: 10.1097/INF.0b013e3181dffabf.
    1. Bermal N, Szenborn L, Edison A, Hernandez M, Pejcz J, Majda-Stanislawska E, et al. Safety and immunogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine coadministered with DTPw-HBV/Hib and poliovirus vaccines. Pediatr Infect Dis J. 2011;30:69–72. doi: 10.1097/INF.0b013e3181f2da06.
    1. Lagos RE, Muñoz AE, Levine MM, Lepetic A, François N, Yarzabal JP, et al. Safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Chilean children. Hum Vaccin. 2011;7:511–22. doi: 10.4161/hv.7.5.14634.
    1. Kim CH, Kim JS, Cha SH, Kim KN, Kim JD, Lee KY, et al. Response to primary and booster vaccination with 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine in Korean infants. Pediatr Infect Dis J. 2011;30:e235–43. doi: 10.1097/INF.0b013e31822a8541.
    1. Prymula R, Peeters P, Chrobok V, Kriz P, Novakova E, Kaliskova E, et al. Pneumococcal capsular polysaccharides conjugated to protein D for prevention of acute otitis media caused by both Streptococcus pneumoniae and non-typable Haemophilus influenzae: a randomised double-blind efficacy study. Lancet. 2006;367:740–8. doi: 10.1016/S0140-6736(06)68304-9.
    1. Hausdorff WP, Hoet B, Schuerman L. Do pneumococcal conjugate vaccines provide any cross-protection against serotype 19A? BMC Pediatr. 2010;10:4. doi: 10.1186/1471-2431-10-4.
    1. De Wals P, Lefebvre B, Defay F, Deceuninck G, Boulianne N. Invasive pneumococcal diseases in birth cohorts vaccinated with PCV-7 and/or PHiD-CV in the province of Quebec, Canada. Vaccine. 2012;30:6416–20. doi: 10.1016/j.vaccine.2012.08.017.
    1. Hoppenbrouwers K, Lagos R, Swennen B, Ethevenaux C, Knops J, Levine MM, et al. Safety and immunogenicity of an Haemophilus influenzae type b-tetanus toxoid conjugate (PRP-T) and diphtheria-tetanus-pertussis (DTP) combination vaccine administered in a dual-chamber syringe to infants in Belgium and Chile. Vaccine. 1998;16:921–7. doi: 10.1016/S0264-410X(97)00303-4.
    1. Lagos R, Hoffenbach A, Scemama M, Dupuy M, Schodel F, Hessel L, et al. Lot-to-lot consistency of a combined hexavalent diptheria-tetanus-acellular-pertussis, hepatitis B, Inactivated polio and haemophilus B conjugate vaccine, administered to healthy chilean infants at two, four and six months of age. Hum Vaccin. 2005;1:112–7. doi: 10.4161/hv.1.3.1848.
    1. Bermal N, Szenborn L, Chrobot A, Alberto E, Lommel P, Gatchalian S, et al. The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) coadministered with DTPw-HBV/Hib and poliovirus vaccines: assessment of immunogenicity. Pediatr Infect Dis J. 2009;28(Suppl):S89–96. doi: 10.1097/INF.0b013e318199f901.
    1. Lee HJ, Huang LM, Togashi T, Juergens C, Amdekar YK, Kieninger DM, et al. Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine: population differences observed in Asian, European, and American paediatric studies. Abstract presented at the 8th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD), Brazil, March 11-15, 2012.
    1. Concepcion NF, Frasch CE. Pneumococcal type 22f polysaccharide absorption improves the specificity of a pneumococcal-polysaccharide enzyme-linked immunosorbent assay. Clin Diagn Lab Immunol. 2001;8:266–72.
    1. Henckaerts I, Goldblatt D, Ashton L, Poolman J. Critical differences between pneumococcal polysaccharide enzyme-linked immunosorbent assays with and without 22F inhibition at low antibody concentrations in pediatric sera. Clin Vaccine Immunol. 2006;13:356–60. doi: 10.1128/CVI.13.3.356-360.2006.
    1. Poolman JT, Frasch CE, Käyhty H, Lestrate P, Madhi SA, Henckaerts I. Evaluation of pneumococcal polysaccharide immunoassays using a 22F adsorption step with serum samples from infants vaccinated with conjugate vaccines. Clin Vaccine Immunol. 2010;17:134–42. doi: 10.1128/CVI.00289-09.
    1. Romero-Steiner S, Libutti D, Pais LB, Dykes J, Anderson P, Whitin JC, et al. Standardization of an opsonophagocytic assay for the measurement of functional antibody activity against Streptococcus pneumoniae using differentiated HL-60 cells. Clin Diagn Lab Immunol. 1997;4:415–22.

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