Immunogenicity, safety, and reactogenicity of combined reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine administered as a booster vaccine dose in healthy Russian participants: a phase III, open-label study

Asmik Asatryan, Nadia Meyer, Michael Scherbakov, Victor Romanenko, Irina Osipova, Anna Galustyan, Olga Shamsheva, Tatiana Latysheva, Tatyana Myasnikova, Nathalie Baudson, Monique Dodet, Stebin Xavier, Lauriane Harrington, Anastasia Kuznetsova, Laura Campora, Peter Van den Steen, Asmik Asatryan, Nadia Meyer, Michael Scherbakov, Victor Romanenko, Irina Osipova, Anna Galustyan, Olga Shamsheva, Tatiana Latysheva, Tatyana Myasnikova, Nathalie Baudson, Monique Dodet, Stebin Xavier, Lauriane Harrington, Anastasia Kuznetsova, Laura Campora, Peter Van den Steen

Abstract

As vaccine-induced immunity and protection following natural pertussis infection wane over time, adults and adolescents may develop pertussis and become transmitters to unprotected infants. In Russia, diphtheria and tetanus but not pertussis-containing vaccines are registered for older children, adolescents, or adults. The reduced-antigen-content diphtheria toxoid, tetanus toxoid, and acellular pertussis (dTpa) vaccine (Boostrix, GSK) was developed for booster vaccination of children ≥4 years of age, adolescents, and adults. A phase III, open-label, non-randomized study was performed in eight centers in Russia between January and July 2018. The objective of this study was to assess immunogenicity, reactogenicity and safety of a single dose of dTpa vaccine in healthy Russian participants ≥4 years of age (age categories 4-9 years, 10-17 years, 18-64 years, and ≥65 years). At 1 month post-booster vaccination, across all age groups, >99.0% of participants were seroprotected against diphtheria and tetanus and >96.0% of participants were seropositive for anti-pertussis antibodies. For all antibodies across all age groups, antibody GMCs increased from pre- to 1 month post-booster vaccination and booster responses to diphtheria (in 71.5% of participants), tetanus (85.3%), and pertussis antigens (≥85.6%) were observed. One serious adverse event that was not causally related to the study vaccine was reported. No fatal cases were reported throughout the study period. In conclusion, administration of the dTpa vaccine as a booster dose in healthy Russian participants induced a robust immune response to all vaccine antigens and was generally well tolerated across all age groups.

Keywords: Acellular pertussis; booster vaccination; diphtheria; immunogenicity; reactogenicity; safety; tetanus.

Figures

Figure 1.
Figure 1.
Participants flow diagram
Figure 2.
Figure 2.
Geometric mean concentration at pre-vaccination and 1 month post-vaccination by age group for anti-D and anti-T antibodies (A) and anti-pertussis antibodies (B) (per protocol cohort for analysis of immunogenicity)
Figure 3.
Figure 3.
Percentage of participants with solicited local adverse events or unsolicited reported during the 4-day (Days 1–4) period after dTpa vaccination (total vaccinated cohort)

References

    1. Centers for Disease Control and Prevention . Epidemiology and prevention of vaccine-preventable diseases. In: Hamborsky J, Kroger A, Wolfe S, editors. Chapter 16: pertussis. 13th ed. Washington D.C.: Public Health Foundation; 2015. [accessed 2019 September3]. .
    1. Centers for Disease Control and Prevention (CDC) 2015 . Epidemiology and prevention of vaccine-preventable diseases, 13th edition; 2015. April. [accessed 2019 September3]. .
    1. Expert opinion on childhood immunisation schedule: diphtheria-tetanus-pertussis (DTP) vaccination. 2009. November 6. [accessed 2019 September3]. .
    1. Yeung KHT, Duclos P, Nelson EAS, Hutubessy RCW.. An update of the global burden of pertussis in children younger than 5 years: a modelling study. Lancet Infect Dis. 2017;17(9):974–80. doi:10.1016/s1473-3099(17)30390-0.
    1. de Greeff SC, Mooi FR, Westerhof A, Verbakel JM, Peeters MF, Heuvelman CJ, Notermans DW, Elvers LH, Schellekens JF, de Melker HE. Pertussis disease burden in the household: how to protect young infants. Clin Infect Dis. 2010;50(10):1339–45. doi:10.1086/652281.
    1. Kowalzik F, Barbosa AP, Fernandes VR, Carvalho PR, Avila-Aguero ML, Goh DY, Goh A, de Miguel JG, Moraga F, Roca J, et al. Prospective multinational study of pertussis infection in hospitalised infants and their household contacts. Pediatr Infect Dis J. 2007;26(3):238–42. doi:10.1097/.
    1. Forsyth K, Plotkin S, Tan T, Wirsing von König CH. Strategies to decrease pertussis transmission to infants. Pediatrics. 2015;135(6):e1475–e1482. doi:10.1542/peds.2014-3925.
    1. European Medicines Agency . List of nationally authorised medicinal products. Active substance(s): diphtheria/tetanus/pertussis (acellular, component) vaccine (adsorbed), diphtheria/tetanus/pertussis (acellular, component) vaccine (adsorbed) reduced antigens contents. [accessed 2019 November22]. .
    1. Boostrix - summary of product characteristics. [accessed 2020. May 15]. .
    1. Van der Wielen M, Van Damme P, Joossens E, Francois G, Meurice F, Ramalho A. A randomised controlled trial with a diphtheria-tetanus-acellular pertussis (dTpa) vaccine in adults. Vaccine. 2000;18(20):2075–82. doi:10.1016/s0264-410x(99)00568-x.
    1. Ward JI, Cherry JD, Chang SJ, Partridge S, Lee H, Treanor J, Greenberg DP, Keitel W, Barenkamp S, Bernstein DI, et al. Efficacy of an acellular pertussis vaccine among adolescents and adults. N Engl J Med. 2005;353(15):1555–63. doi:10.1056/NEJMoa050824.
    1. Ward JI, Cherry JD, Chang SJ, Partridge S, Keitel W, Edwards K, Lee M, Treanor J, Greenberg DP, Barenkamp S, et al. Bordetella Pertussis infections in vaccinated and unvaccinated adolescents and adults, as assessed in a national prospective randomized Acellular Pertussis Vaccine Trial (APERT). Clin Infect Dis. 2006;43(2):151–57. doi:10.1086/504803.
    1. World Health Organization . WHO vaccine-preventable diseases: monitoring system. 2019 global summary. [accessed 2019 September3]. .
    1. Appendix. National Immunization Calendar of the Russian Federation.” National Research Council . Biological science and biotechnology in russia: controlling diseases and enhancing security. Washington (DC): The National Academies Press; 2006. doi:10.17226/11382.
    1. Camargo ME, Silveira L, Furuta JA, Oliveira EP, Germek OA. Immunoenzymatic assay of anti-diphtheric toxin antibodies in human serum. J Clin Microbiol. 1984;20(4):772–74. doi:10.1128/JCM.20.4.772-774.1984.
    1. Melville-Smith ME, Seagroatt VA, Watkins JT. A comparison of enzyme-linked immunosorbent assay (ELISA) with the toxin neutralization test in mice as a method for the estimation of tetanus antitoxin in human sera. J Biol Stand. 1983;11(2):137–44. doi:10.1016/s0092-1157(83)80038-9.
    1. Efstratiou A, Maple CPA, World Health Organization . Regional Office for Europe. Laboratory diagnosis of diphtheria. Copenhagen: WHO Regional Office for Europe; 1994. .
    1. Meyer CU, Habermehl P, Knuf M, Hoet B, Wolter J, Zepp F. Immunogenicity and reactogenicity of acellular pertussis booster vaccines in children: standard pediatric versus a reduced-antigen content formulation. Hum Vaccin. 2008;4(3):203–09. doi:10.4161/hv.4.3.5290.
    1. Huang LM, Chang LY, Tang H, Bock HL, Lu CY, Huang FY, Lin TY, Lee CY. Immunogenicity and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine in healthy Taiwanese children and adolescents. J Adolesc Health. 2005;37(6):517. doi:10.1016/j.jadohealth.2005.08.009.
    1. Pichichero ME, Blatter MM, Kennedy WA, Hedrick J, Descamps D, Friedland LR. Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids for adolescents. Pediatrics. 2006;117(4):1084–93. doi:10.1542/peds.2005-1759.
    1. Tran Minh NN, He Q, Ramalho A, Kaufhold A, Viljanen MK, Arvilommi H, Mertsola J. Acellular vaccines containing reduced quantities of pertussis antigens as a booster in adolescents. Pediatrics. 1999;104(6):e70. doi:10.1542/peds.104.6.e70.
    1. Di Pasquale A, Wolter J, Schuerman L. Management of pertussis in adolescents and adults: the role of a reduced-antigen content combined diphtheria-tetanus-acellular pertussis (dTap) vaccine. J Prev Med Hyg. 2005;46:33–41.
    1. Booy R, Van der Meeren O, Ng SP, Celzo F, Ramakrishnan G, Jacquet JM. A decennial booster dose of reduced antigen content diphtheria, tetanus, acellular pertussis vaccine (Boostrix™) is immunogenic and well tolerated in adults. Vaccine. 2010;29(1):45–50. doi:10.1016/j.vaccine.2010.10.025.
    1. Theeten H, Rümke H, Hoppener FJ, Vilatimó R, Narejos S, Van Damme P, Hoet B. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines. Curr Med Res Opin. 2007;23(11):2729–39. doi:10.1185/03007x233034.
    1. Nguyen V, Mendelsohn A, Larrick JW. Interleukin-7 and Immunosenescence. J Immunol Res. 2017;2017:4807853. doi:10.1155/2017/4807853.
    1. Kurova N, Timofeeva EV, Guiso N, Macina D. Russia SP. A cross-sectional study of Bordetella pertussis seroprevalence and estimated duration of vaccine protection against pertussis in St. Petersburg, Russia. Vaccine. 2018;36(52):7936–42. doi:10.1016/j.vaccine.2018.11.007.
    1. Borisova O, Kombarova SY, Zakharova NS, van Gent M, Aleshkin VA, Mazurova I, Mooi FR. Antigenic divergence between Bordetella pertussis clinical isolates from Moscow, Russia, and vaccine strains. Clin Vaccine Immunol. 2007;14(3):234–38. doi:10.1128/cvi.00294-06.
    1. Mertsola J, Van Der Meeren O, He Q, Linko-Parvinen A, Ramakrishnan G, Mannermaa L, Soila M, Pulkkinen M, Jacquet JM. Decennial administration of a reduced antigen content diphtheria and tetanus toxoids and acellular pertussis vaccine in young adults. Clin Infect Dis. 2010;51(6):656–62. doi:10.1086/655825.
    1. Brandon D, Kimmel M, Kuriyakose SO, Kostanyan L, Mesaros N. Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults. Vaccine. 2018;36(42):6325–33. doi:10.1016/j.vaccine.2018.08.051.
    1. Van Damme P, Burgess M. Immunogenicity of a combined diphtheria-tetanus-acellular pertussis vaccine in adults. Vaccine. 2004;22(3–4):305–08. doi:10.1016/j.vaccine.2003.08.012.
    1. Zepp F, Cheuvart B, Wolter JM. Anti-diphtheria antibodies should persist until adolescence after a reduced-antigen diphtheria, tetanus and acellular pertussis vaccine (dTpa) in pre-school-aged children. Paper presented at: 21st Annual meeting of the european society for paediatric infectious diseases; 2003. April 9-11; Giardini Naxos, Taormina, Sicily, Italy.
    1. Rennels MB. Extensive swelling reactions occurring after booster doses of diphtheria-tetanus-acellular pertussis vaccines. Semin Pediatr Infect Dis. 2003;14(3):196–98. doi:10.1016/s1045-1870(03)00033-5.
    1. Pichichero ME, Deloria MA, Rennels MB, Anderson EL, Edwards KM, Decker MD, Englund JA, Steinhoff MC, Deforest A, Meade BD. A safety and immunogenicity comparison of 12 acellular pertussis vaccines and one whole-cell pertussis vaccine given as a fourth dose in 15- to 20-month-old children. Pediatrics. 1997;100(5):772–88. doi:10.1542/peds.100.5.772.
    1. Woo EJ, Burwen DR, Gatumu SNM, Ball R, Group TVAERSW . Extensive Limb Swelling after Immunization: reports to the Vaccine Adverse Event Reporting System. Clin Infect Dis. 2003;37(3):351–58. doi:10.1086/375820.
    1. European Medicines Agency . Boostrix. Summary or product characteristics. [accessed 2019 November6]. .
    1. Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. The how’s and what’s of vaccine reactogenicity. NPJ Vaccines. 2019;4(1):39. doi:10.1038/s41541-019-0132-6.

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