Safety and Immunogenicity of Pneumococcal Conjugate Vaccines in a High-risk Population: A Randomized Controlled Trial of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccine in Papua New Guinean Infants

William S Pomat, Anita H J van den Biggelaar, Sandra Wana, Jacinta P Francis, Vela Solomon, Andrew R Greenhill, Rebecca Ford, Tilda Orami, Megan Passey, Peter Jacoby, Lea-Ann Kirkham, Deborah Lehmann, Peter C Richmond, 10v13v PCV Trial Team, L Bele, M Dreyam, A Elizah, R Ford, J Francis, A Gihigupa, A Greenhill, S Javati, J Kave, W Kirarock, M Lai, B Martin, G Masiria, A Michael, L Moliki, B Nagepu, M Nenikuro, B Nivio, C Opa, T Orami, W S Pomat, G Saleu, P Siba, V Solomon, S Wana, L Wawae, M Yoannes, I Hwaihwanje, T Korowi, C Mond, P Wari, P Jacoby, D Lehmann, A van den Biggelaar, K Corscadden, C de Gier, L Kirkham, T Rahman, P Richmond, R Thornton, M Passey, William S Pomat, Anita H J van den Biggelaar, Sandra Wana, Jacinta P Francis, Vela Solomon, Andrew R Greenhill, Rebecca Ford, Tilda Orami, Megan Passey, Peter Jacoby, Lea-Ann Kirkham, Deborah Lehmann, Peter C Richmond, 10v13v PCV Trial Team, L Bele, M Dreyam, A Elizah, R Ford, J Francis, A Gihigupa, A Greenhill, S Javati, J Kave, W Kirarock, M Lai, B Martin, G Masiria, A Michael, L Moliki, B Nagepu, M Nenikuro, B Nivio, C Opa, T Orami, W S Pomat, G Saleu, P Siba, V Solomon, S Wana, L Wawae, M Yoannes, I Hwaihwanje, T Korowi, C Mond, P Wari, P Jacoby, D Lehmann, A van den Biggelaar, K Corscadden, C de Gier, L Kirkham, T Rahman, P Richmond, R Thornton, M Passey

Abstract

Background: There are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population.

Methods: PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age.

Results: One month after the third dose of PCV10 or PCV13, ˃80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85-96) of children vaccinated with PCV10 and 81% (95% CI 72-88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events.

Conclusions: Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed.

Clinical trials registration: NCT01619462.

Keywords: S. pneumonia; Papua New Guinea; antibodies; carriage; pneumococcal conjugate vaccine.

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Flowchart. HIV, human immunodeficiency virus; LTFU, lost to follow-up; Mig, Migration; PCV10, 10-valent pneumococcal conjugate vaccine; PCV13, 13-valent pneumococcal conjugate vaccine; PV, protocol violation; WC, withdrawn consent.
Figure 2.
Figure 2.
GMCs of serotype-specific IgG antibodies. GMCs and 95% CIs for IgG antibodies against shared PCV10/13 serotypes, (*) PCV13-only serotypes, and (**) non-PCV serotype 2 measured before vaccination, at 4 months of age, and at 9 months of age were compared between children vaccinated with either three doses of PCV10 (orange square) or PCV13 (blue circle) using a 2-sample t-test and indicated with (#) when significantly different (P

Figure 3.

GM fold change in PCV-induced…

Figure 3.

GM fold change in PCV-induced IgG responses between 4 and 9 months of…

Figure 3.
GM fold change in PCV-induced IgG responses between 4 and 9 months of age. GM fold changes and 95% CIs in vaccine-induced IgG antibody titers between 4 and 9 months of age were calculated for shared PCV10/13 serotypes for both PCV10- (orange square) and PCV13- (blue circle) vaccinated children, as well as for PCV13-only serotypes (*) for the PCV13-vaccinated group. GMs and 95% CIs P < .05) decline in antibody responses. GM fold changes were compared between the groups for each shared vaccine serotype using a 2-sample t-test and when a significant difference was found P-values were included. Abbreviations: CI, confidence interval; GM, geometric mean; IgG, immunoglobulin G; PCV, pneumococcal conjugate vaccine.
Figure 3.
Figure 3.
GM fold change in PCV-induced IgG responses between 4 and 9 months of age. GM fold changes and 95% CIs in vaccine-induced IgG antibody titers between 4 and 9 months of age were calculated for shared PCV10/13 serotypes for both PCV10- (orange square) and PCV13- (blue circle) vaccinated children, as well as for PCV13-only serotypes (*) for the PCV13-vaccinated group. GMs and 95% CIs P < .05) decline in antibody responses. GM fold changes were compared between the groups for each shared vaccine serotype using a 2-sample t-test and when a significant difference was found P-values were included. Abbreviations: CI, confidence interval; GM, geometric mean; IgG, immunoglobulin G; PCV, pneumococcal conjugate vaccine.

References

    1. World Health Organization. Immunization coverage. Fact sheet Available at: . Accessed 31 August 2017.
    1. The Boston Consulting Group, The Vaccine Alliance. The advance market commitment pilot for pneumococcal vaccines: outcomes and impact evaluation, 2015. Available at: . Accessed 12 December 2017.
    1. Prymula R, Peeters P, Chrobok V, 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.
    1. Mudhune S, Wamae M; Network Surveillance for Pneumococcal Disease in the East African Region Report on invasive disease and meningitis due to Haemophilus influenzae and Streptococcus pneumonia from the Network for Surveillance of Pneumococcal Disease in the East African Region. Clin Infect Dis 2009; 48 Suppl 2:S147–52.
    1. Van Eldere J, Slack MP, Ladhani S, Cripps AW. Non-typeable Haemophilus influenzae, an under-recognised pathogen. Lancet Infect Dis 2014; 14:1281–92.
    1. Mackenzie GA, Hill PC, Jeffries DJ, et al. . Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study. Lancet Infect Dis 2016; 16:703–11.
    1. Plosker GL. 10-Valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine: a review in infants and children. Paediatr Drugs 2014; 16:425–44.
    1. Nguyen L, Cohen O, O’Brien KL. State of PCV use and impact evaluation. A strategic gap analysis of the global evidence from published and ongoing impact studies evaluating routine PCV use Available at: . Accessed 31 August 2017.
    1. Johnson HL, Deloria-Knoll M, Levine OS, et al. . Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project. PLoS Med 2010; 7. doi:10.1371/journal.pmed.1000348
    1. Pomat WS, van den Biggelaar AH, Phuanukoonnon S, et al. . Pneumococcal Conjugate Vaccine Trial Study Team Safety and immunogenicity of neonatal pneumococcal conjugate vaccination in Papua New Guinean children: a randomised controlled trial. PLoS One 2013; 8:e56698.
    1. Blyth CC, Ford R, Sapura J, et al. ; Papua New Guinea Pneumonia and Meningitis Etiology Study Team Childhood pneumonia and meningitis in the Eastern Highlands Province, Papua New Guinea in the era of conjugate vaccines: study methods and challenges. Pneumonia 2017; 9:5.
    1. Lehmann D, Kirarock W, van den Biggelaar AHJ, et al. ; 10v13v PCV trial team Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea. Pneumonia 2017; 9:20.
    1. Balloch A, Licciardi PV, Leach A, Nurkka A, Tang ML. Results from an inter-laboratory comparison of pneumococcal serotype-specific IgG measurement and critical parameters that affect assay performance. Vaccine 2010; 28:1333–40.
    1. World Health Organization Pneumoccal Serology Reference Laboratories. Training manual for enzyme linked immunosorbent assay for the quantitation of Streptococcus pneumoniae serotype specific IgG (Pn PS ELISA) Available at: . Accessed 1 June 2017.
    1. Goldblatt D, Plikaytis BD, Akkoyunlu M, et al. . Establishment of a new human pneumococcal standard reference serum, 007sp. Clin Vaccine Immunol 2011; 18:1728–36.
    1. Siber GR, Chang I, Baker S, et al. . Estimating the protective concentration of anti-pneumococcal capsular polysaccharide antibodies. Vaccine 2007; 25:3816–26.
    1. O’Brien KL, Nohynek H; World Health Organization Pneumococcal Vaccine Trials Carraige Working Group Report from a WHO working group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae. Pediatr Infect Dis J 2003; 22:133–40.
    1. Trück J, Snape MD, Tatangeli F, et al. . Pneumococcal serotype-specific antibodies persist through early childhood after infant immunization: follow-up from a randomized controlled trial. PLoS One 2014; 9:e91413.
    1. Russell FM, Carapetis JR, Balloch A, et al. . Hyporesponsiveness to re-challenge dose following pneumococcal polysaccharide vaccine at 12 months of age: a randomized controlled trial. Vaccine 2010; 28:3341–9.
    1. van den Biggelaar AHJ, Richmond PC, Fuery A, et al. . Pneumococcal responses are similar in Papua New Guinean children aged 3–5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination. PLoS One 2017; 12:e0185877.
    1. Aho C, Michael A, Yoannes M, et al. ; Neonatal Pneumococcal Conjugate Vaccine Trial Study Team Limited impact of neonatal or early infant schedules of 7-valent pneumococcal conjugate vaccination on nasopharyngeal carriage of Streptococcus pneumoniae in Papua New Guinean children: a randomized controlled trial. Vaccine Rep 2016; 6:36–43.
    1. Scott JA, Ojal J, Ashton L, Muhoro A, Burbidge P, Goldblatt D. Pneumococcal conjugate vaccine given shortly after birth stimulates effective antibody concentrations and primes immunological memory for sustained infant protection. Clin Infect Dis 2011; 53:663–70.
    1. Ojal J, Goldblatt D, Tigoi C, Scott JAG. Effect of maternally-derived anti-protein and anti-capsular IgG antibodies on the rate of acquisition of nasopharyngeal carriage of pneumococcus in newborns. Clin Infect Dis 2017; 66:121–30.
    1. Hanke CR, Grijalva CG, Chochua S, et al. . Bacterial density, serotype distribution and antibiotic resistance of pneumococcal strains from the nasopharynx of Peruvian children before and after pneumococcal conjugate vaccine 7. Pediatr Infect Dis J 2016; 35:432–9.
    1. Olwagen CP, Adrian PV, Nunes MC, Madhi SA. Evaluation of the association of pneumococcal conjugate vaccine immunization and density of nasopharyngeal bacterial colonization using a multiplex quantitative polymerase chain reaction assay. Vaccine 2018; 36:3278–85.
    1. Francis JP, Richmond PC, Pomat WS, et al. . Maternal antibodies to pneumolysin but not to pneumococcal surface protein A delay early pneumococcal carriage in high-risk Papua New Guinean infants. Clin Vaccine Immunol 2009; 16:1633–8.
    1. Ojal J, Hammitt LL, Gaitho J, Scott JAG, Goldblatt D. Pneumococcal conjugate vaccine induced IgG and nasopharyngeal carriage of pneumococci: hyporesponsiveness and immune correlates of protection for carriage. Vaccine 2017; 35:4652–7.
    1. Dagan R, Givon-Lavi N, Greenberg D, Fritzell B, Siegrist CA. Nasopharyngeal carriage of Streptococcus pneumoniae shortly before vaccination with a pneumococcal conjugate vaccine causes serotype-specific hyporesponsiveness in early infancy. J Infect Dis 2010; 201:1570–9.
    1. Saokaew S, Rayanakorn A, Wu DB, Chaiyakunapruk N. Cost Effectiveness of pneumococcal vaccination in children in low- and middle-income countries: a systematic review. PharmacoEcon 2016; 34:1211–25.
    1. Chan J, Nguyen CD, Lai JYR, et al. . Determining the pneumococcal conjugate vaccine coverage required for indirect protection against vaccine-type pneumococcal carriage in low- and middle-income countries: a protocol for a prospective observational study. BMJ Open 2018; 8:e021512.

Source: PubMed

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