Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Seasonal Influenza Vaccine in Young Children at High Risk of Influenza-associated Complications: A Phase III, Randomized, Observer-blind, Multicenter Clinical Trial

Overview

Journal Pediatr Infect Dis J

Specialty Pediatrics

Date 2020 May 15

PMID 32404782

Citations 2

Authors

Susanna Esposito

John Fling

Kulkanya Chokephaibulkit

Marianne de Bruijn

Janine Oberye

Bin Zhang

Jeanique Vossen

Esther Heijnen

Igor Smolenov

Affiliations

Soon will be listed here.

Abstract

Background: Vaccination against seasonal influenza is recommended for all children with a history of medical conditions placing them at increased risk of influenza-associated complications. The immunogenicity and efficacy of conventional influenza vaccines among young children are suboptimal; one strategy to enhance these is adjuvantation. We present immunogenicity and safety data for an MF59-adjuvanted quadrivalent influenza vaccine (aIIV4) in healthy children and those at a high risk of influenza-associated complications, based on the results of a recently completed phase III study.

Methods: Children 6 months to 5 years of age (N = 10,644) were enrolled. The study was conducted across northern hemisphere seasons 2013-2014 and 2014-2015. Subjects received either aIIV4 or a nonadjuvanted comparator influenza vaccine. Antibody responses were assessed by hemagglutination inhibition assay against vaccine and heterologous strains. Long-term antibody persistence was assessed (ClinicalTrials.gov: NCT01964989).

Results: aIIV4 induced significantly higher antibody titers than nonadjuvanted vaccine in high-risk subjects. aIIV4 antibody responses were of similar magnitude in high-risk and healthy subjects. Incidence of solicited local and systemic adverse events (AEs) was slightly higher in aIIV4 than nonadjuvanted vaccinees, in both the healthy and high-risk groups. Incidence of unsolicited AEs, serious AEs and AEs of special interest were similar for adjuvanted and nonadjuvanted vaccinees in the healthy and high-risk groups.

Conclusion: aIIV4 was more immunogenic than nonadjuvanted vaccine in both the healthy and high-risk study groups. The reactogenicity and safety profiles of aIIV4 and the nonadjuvanted vaccine were acceptable and similar in 6-month- to 5-year-old high-risk and healthy children.

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References

Vesikari T, Kirstein J, Go G, Leav B, Ruzycky M, Isakov L . Efficacy, immunogenicity, and safety evaluation of an MF59-adjuvanted quadrivalent influenza virus vaccine compared with non-adjuvanted influenza vaccine in children: a multicentre, randomised controlled, observer-blinded, phase 3 trial. Lancet Respir Med. 2018; 6(5):345-356. DOI: 10.1016/S2213-2600(18)30108-5. View

Thorrington D, van Leeuwen E, Ramsay M, Pebody R, Baguelin M . Cost-effectiveness analysis of quadrivalent seasonal influenza vaccines in England. BMC Med. 2017; 15(1):166. PMC: 5590113. DOI: 10.1186/s12916-017-0932-3. View

Baldo V, Baldovin T, Floreani A, Carraro A, Trivello R . MF59-adjuvanted influenza vaccine confers superior immunogenicity in adult subjects (18-60 years of age) with chronic diseases who are at risk of post-influenza complications. Vaccine. 2007; 25(20):3955-61. DOI: 10.1016/j.vaccine.2007.02.045. View

Louie J, Acosta M, Samuel M, Schechter R, Vugia D, Harriman K . A novel risk factor for a novel virus: obesity and 2009 pandemic influenza A (H1N1). Clin Infect Dis. 2011; 52(3):301-12. DOI: 10.1093/cid/ciq152. View

Khurana S, Chearwae W, Castellino F, Manischewitz J, King L, Honorkiewicz A . Vaccines with MF59 adjuvant expand the antibody repertoire to target protective sites of pandemic avian H5N1 influenza virus. Sci Transl Med. 2010; 2(15):15ra5. DOI: 10.1126/scitranslmed.3000624. View

OHagan D, Ott G, De Gregorio E, Seubert A . The mechanism of action of MF59 - an innately attractive adjuvant formulation. Vaccine. 2012; 30(29):4341-8. DOI: 10.1016/j.vaccine.2011.09.061. View

Kumar D, Campbell P, Hoschler K, Hidalgo L, Al-Dabbagh M, Wilson L . Randomized Controlled Trial of Adjuvanted Versus Nonadjuvanted Influenza Vaccine in Kidney Transplant Recipients. Transplantation. 2015; 100(3):662-9. DOI: 10.1097/TP.0000000000000861. View

Esposito S, Pugni L, Daleno C, Ronchi A, Valzano A, Serra D . Influenza A/H1N1 MF59-adjuvanted vaccine in preterm and term children aged 6 to 23 months. Pediatrics. 2011; 127(5):e1161-8. DOI: 10.1542/peds.2010-1920. View

Nolan T, Bravo L, Ceballos A, Mitha E, Gray G, Quiambao B . Enhanced and persistent antibody response against homologous and heterologous strains elicited by a MF59-adjuvanted influenza vaccine in infants and young children. Vaccine. 2014; 32(46):6146-56. DOI: 10.1016/j.vaccine.2014.08.068. View

10.

Caini S, Huang Q, Ciblak M, Kusznierz G, Owen R, Wangchuk S . Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study. Influenza Other Respir Viruses. 2015; 9 Suppl 1:3-12. PMC: 4549097. DOI: 10.1111/irv.12319. View

11.

Cromer D, van Hoek A, Jit M, Edmunds W, Fleming D, Miller E . The burden of influenza in England by age and clinical risk group: a statistical analysis to inform vaccine policy. J Infect. 2013; 68(4):363-71. DOI: 10.1016/j.jinf.2013.11.013. View

12.

Wong K, Jain S, Blanton L, Dhara R, Brammer L, Fry A . Influenza-associated pediatric deaths in the United States, 2004-2012. Pediatrics. 2013; 132(5):796-804. PMC: 6027595. DOI: 10.1542/peds.2013-1493. View

13.

Vesikari T, Knuf M, Wutzler P, Karvonen A, Kieninger-Baum D, Schmitt H . Oil-in-water emulsion adjuvant with influenza vaccine in young children. N Engl J Med. 2011; 365(15):1406-16. DOI: 10.1056/NEJMoa1010331. View

14.

Trombetta C, Gianchecchi E, Montomoli E . Influenza vaccines: Evaluation of the safety profile. Hum Vaccin Immunother. 2018; 14(3):657-670. PMC: 5861790. DOI: 10.1080/21645515.2017.1423153. View

15.

Sheridan P, Paich H, Handy J, Karlsson E, Hudgens M, Sammon A . Obesity is associated with impaired immune response to influenza vaccination in humans. Int J Obes (Lond). 2011; 36(8):1072-7. PMC: 3270113. DOI: 10.1038/ijo.2011.208. View

16.

DellEra L, Corona F, Daleno C, Scala A, Principi N, Esposito S . Immunogenicity, safety and tolerability of MF59-adjuvanted seasonal influenza vaccine in children with juvenile idiopathic arthritis. Vaccine. 2011; 30(5):936-40. DOI: 10.1016/j.vaccine.2011.11.083. View

17.

Iorio A, Francisci D, Camilloni B, Stagni G, De Martino M, Toneatto D . Antibody responses and HIV-1 viral load in HIV-1-seropositive subjects immunised with either the MF59-adjuvanted influenza vaccine or a conventional non-adjuvanted subunit vaccine during highly active antiretroviral therapy. Vaccine. 2003; 21(25-26):3629-37. DOI: 10.1016/s0264-410x(03)00408-0. View

18.

Plessa E, Diakakis P, Gardelis J, Thirios A, Koletsi P, Falagas M . Clinical features, risk factors, and complications among pediatric patients with pandemic influenza A (H1N1). Clin Pediatr (Phila). 2010; 49(8):777-81. DOI: 10.1177/0009922810368558. View

19.

Patel S, Bizjajeva S, Heijnen E, Oberye J . MF59-adjuvanted seasonal trivalent inactivated influenza vaccine: Safety and immunogenicity in young children at risk of influenza complications. Int J Infect Dis. 2019; 85S:S18-S25. DOI: 10.1016/j.ijid.2019.04.023. View

20.

Khurana S, Coyle E, Dimitrova M, Castellino F, Nicholson K, Del Giudice G . Heterologous prime-boost vaccination with MF59-adjuvanted H5 vaccines promotes antibody affinity maturation towards the hemagglutinin HA1 domain and broad H5N1 cross-clade neutralization. PLoS One. 2014; 9(4):e95496. PMC: 3995799. DOI: 10.1371/journal.pone.0095496. View