Publication: Antibody persistence after vaccination of adolescents with monovalent and combined acellular pertussis vaccines containing genetically inactivated pertussis toxin: a phase 2/3 randomised, controlled, non-inferiority trial
Issued Date
2018-11-01
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14744457
14733099
14733099
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2-s2.0-85056483314
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Mahidol University
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SCOPUS
Bibliographic Citation
The Lancet Infectious Diseases. Vol.18, No.11 (2018), 1260-1268
Suggested Citation
Punnee Pitisuttithum, Kulkanya Chokephaibulkit, Chukiat Sirivichayakul, Sirintip Sricharoenchai, Jittima Dhitavat, Arom Pitisuthitham, Wanatpreeya Phongsamart, Kobporn Boonnak, Keswadee Lapphra, Yupa Sabmee, Orasri Wittawatmongkol, Mukesh Chauhan, Wassana Wijagkanalan, Greanggrai Hommalai, Librada Fortuna, Pailinrut Chinwangso, Indrajeet Kumar Poredi, Anita H.J. van den Biggelaar, Hong Thai Pham, Simonetta Viviani Antibody persistence after vaccination of adolescents with monovalent and combined acellular pertussis vaccines containing genetically inactivated pertussis toxin: a phase 2/3 randomised, controlled, non-inferiority trial. The Lancet Infectious Diseases. Vol.18, No.11 (2018), 1260-1268. doi:10.1016/S1473-3099(18)30375-X Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/46205
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Title
Antibody persistence after vaccination of adolescents with monovalent and combined acellular pertussis vaccines containing genetically inactivated pertussis toxin: a phase 2/3 randomised, controlled, non-inferiority trial
Author(s)
Punnee Pitisuttithum
Kulkanya Chokephaibulkit
Chukiat Sirivichayakul
Sirintip Sricharoenchai
Jittima Dhitavat
Arom Pitisuthitham
Wanatpreeya Phongsamart
Kobporn Boonnak
Keswadee Lapphra
Yupa Sabmee
Orasri Wittawatmongkol
Mukesh Chauhan
Wassana Wijagkanalan
Greanggrai Hommalai
Librada Fortuna
Pailinrut Chinwangso
Indrajeet Kumar Poredi
Anita H.J. van den Biggelaar
Hong Thai Pham
Simonetta Viviani
Kulkanya Chokephaibulkit
Chukiat Sirivichayakul
Sirintip Sricharoenchai
Jittima Dhitavat
Arom Pitisuthitham
Wanatpreeya Phongsamart
Kobporn Boonnak
Keswadee Lapphra
Yupa Sabmee
Orasri Wittawatmongkol
Mukesh Chauhan
Wassana Wijagkanalan
Greanggrai Hommalai
Librada Fortuna
Pailinrut Chinwangso
Indrajeet Kumar Poredi
Anita H.J. van den Biggelaar
Hong Thai Pham
Simonetta Viviani
Other Contributor(s)
Abstract
© 2018 Elsevier Ltd Background: The immunogenicity of acellular pertussis vaccines and persistence of immunity after vaccination might be improved by using genetically inactivated pertussis toxin (PTgen) instead of chemically inactivated pertussis toxin (PTchem) because of the preservation of conformational epitopes. We assessed the safety and immunogenicity of two vaccines containing PTgen 1 year after vaccination. Methods: We did a phase 2/3 non-inferiority, randomised, controlled trial involving 450 adolescents (age 12–17 years) enrolled between July 6, 2015, and Aug 20, 2015. Participants were randomised 1:1:1 to receive one dose of vaccine containing PTgen and filamentous haemagglutinin (FHA) either in a monovalent formulation (aP[PTgen/FHA]) or in a combined formulation with tetanus and reduced-dose diphtheria toxoids (TdaP[PTgen/FHA]) or to receive a commercial vaccine containing reduced-dose PTchem (Tdap) as a comparator. We report a secondary trial outcome, namely antibody persistence 1 year after vaccination, assessed per protocol in 150 randomly preselected participants (50 per group). Seroconversion was defined as antibody titres at least four times greater than at baseline. Safety was assessed in all trial participants. This study is registered in the Thai Clinical Trial Registry, number TCTR20150703002. Findings: Between June 5, 2016, and Aug 9, 2016, 442 (98%) of 450 enrolled participants attended a 1-year follow-up visit. After 1 year, persistent seroconversion for pertussis toxin neutralising antibodies was seen in 38 (76%, 95% CI 64–88) participants in the aP(PTgen/FHA) group and 41 (81%, 70–92) in the TdaP(PTgen/FHA) group, but in only four (8%, 1–16) in the Tdap comparator group. Seroconversion rates for IgG antibodies against pertussis toxin and FHA were also greater in the aP(PTgen/FHA) group (82%, 95% CI 71–93 and 64%, 51–77, respectively) and TdaP(PTgen/FHA) group (75%, 63–87 and 56%, 42–70, respectively) than in the Tdap group (4%, 0–9, p<0·0001, and 28%, 16–41, p=0·0007, respectively). 13 serious adverse events were reported in 12 participants and all were judged to be unrelated to the study vaccines. Five pregnancies were reported during follow-up, none of which had any maternal or neonatal complications. Interpretation: A monovalent and a combined recombinant acellular pertussis vaccine containing PTgen induced antibody responses that were greater and sustained for longer than those achieved with the Tdap comparator vaccine. New recombinant pertussis vaccines containing PTgen might offer new opportunities to limit pertussis resurgence and can be widely used, including in pregnant women. Funding: BioNet-Asia.