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Clinical Trial
. 2023 Jul 12;41(31):4541-4553.
doi: 10.1016/j.vaccine.2023.06.001. Epub 2023 Jun 15.

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in pregnant women

Thanyawee Puthanakit  1 , Kulkanya Chokephaibulkit  2 , Surasith Chaithongwongwatthana  3 , Niranjan Bhat  4 , Yuxiao Tang  4 , Suvaporn Anugulruengkitt  1 , Chenchit Chayachinda  5 , Sanitra Anuwutnavin  5 , Keswadee Lapphra  6 , Supattra Rungmaitree  6 , Monta Tawan  1 , Indah Andi-Lolo  4 , Renee Holt  4 , Librada Fortuna  7 , Chawanee Kerdsomboon  8 , Vilasinee Yuwaree  8 , Souad Mansouri  8 , Pham Hong Thai  8 , Bruce L Innis  4
Affiliations
Clinical Trial

A phase 2 randomized controlled dose-ranging trial of recombinant pertussis booster vaccines containing genetically inactivated pertussis toxin in pregnant women

Thanyawee Puthanakit et al. Vaccine. .

Abstract

Introduction: Despite a decrease in infections caused by Bordetella pertussis due to COVID-19 pandemic, booster vaccination of pregnant women is still recommended to protect newborns. Highly immunogenic vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) may generate comparable anti-PT antibody concentrations, even at lower doses, to chemically inactivated acellular pertussis vaccines (Tdapchem) shown effective for maternal immunization.

Methods: This phase 2 randomized, observer-blind, active-controlled non-inferiority trial was conducted in healthy Thai pregnant women randomly assigned to receive one dose of low-dose recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or tetanus, reduced-dose diphtheria combined with ap1gen (Tdap1gen), or combined with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®) or comparator containing 8 µg of chemically inactivated pertussis toxoid, 8 µg FHA, and 2.5 µg pertactin (Boostrix™, Tdap8chem). Blood was collected at Day 0 and Day 28 post-vaccination. The non-inferiority of the study vaccines was assessed based on anti-PT IgG antibody levels on Day 28 pooled with results from a similarly structured previous trial in non-pregnant women.

Results: 400 healthy pregnant women received one dose of vaccine. Combined with data from 250 non-pregnant women, all study vaccines containing PTgen were non-inferior to comparator vaccine (Tdap8chem). Both ap1gen and TdaP5gen vaccines could be considered to have superior immunogenicity to Tdap8chem. Local and systemic solicited reactions were similar among all vaccine groups.

Conclusions: Vaccine formulations containing PTgen were safe and immunogenic in pregnant women. The ap1gen vaccine, with the lowest cost and reactogenicity, may be suitable for use in pregnant women when diphtheria and tetanus toxoids are not needed. This study is registered in the Thai Clinical Trial Registry (www.

Clinicaltrials: in.th), number TCTR20180725004.

Keywords: Genetically inactivated; Immunogenicity; Maternal immunization; Pertussis; Recombinant pertussis vaccine; Safety.

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Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Librada Fortuna, Chawanee Kerdsomboon, Vilasinee Yuwaree, Souad Mansouri and Pham Hong Thai are employed by BioNet. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Study design. Pregnant women were given one dose of study vaccine between ≥20 weeks and <33 weeks gestational age. Local and systemic reactions were collected within 7 days after vaccination. The safety assessment was performed by active follow-up until Visit 4 (2 months after delivery) and by passive follow-up until Visit 10 (13 months after delivery). The blood sample collection for immunogenicity assessment was performed at Visit 1 (before vaccination), Visit 2 (28 days after vaccination) and Visit 3 (delivery). The growth and development assessment and safety assessment for infants were performed at Visit 3 (delivery) until Visit 10 (13 months of infant age). Infants received DTwP-Hib-HB vaccine at 2, 4 and 6 months of age and Pneumococcal 13-valent conjugate vaccine (PCV) at 2, 4 and 12 months of age as primary infant immunization. The cord blood sample at delivery and infant blood sample at Visit 4 (2 months of age), Visit 6 (5 months of age), Visit 8 (7 months of age) and Visit 10 (13 months of age) were collected for immunogenicity assessment.
Fig. 2a
Fig. 2a
Trial profile (pregnant women).
Fig. 2b
Fig. 2b
Pooled population of pregnant women and non-pregnant women of childbearing age.
Fig. 3
Fig. 3
Anti-PT IgG, anti-FHA IgG, and PT-neutralizing antibody seroresponse rate and anti-TT IgG, anti-DT IgG seroprotection rate at 28 days after vaccination in pregnant women.
Fig. A1
Fig. A1
Reverse cumulative distribution curves (RCDCs) for PT-IgG, FHA-IgG and PT neutralizing antibody at baseline and 28 days post-vaccination with study group (ap1gen/Tdap1gen/Tdap2gen/TdaP5gen) and comparator group (Tdap8chem) in pregnant women. Panel A and B represent the RCDC for PT-IgG at baseline and day 28 post-vaccination. Panel C and D represent the RCDC for FHA-IgG at baseline and day 28 post-vaccination. Panel E and F represent the RCDC for PT neutralizing antibody titer at baseline and day 28 post-vaccination.
Fig. A2
Fig. A2
Anti-PT IgG geometric mean concentration (GMCs) at Day 28 post-vaccination between mothers vaccinated at 2nd and 3rd trimester of pregnancy.
See this image and copyright information in PMC

References

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