Geert Leroux-Roels1, Pierre Van Damme2, Wouter Haazen3, Sepehr Shakib4, Magalie Caubet5, Emmanuel Aris6, Jeanne-Marie Devaster7, Mathieu Peeters8. 1. Center for Vaccinology, Ghent University and Ghent University Hospital, BC001, De Pintelaan 185, B-9000 Ghent, Belgium. Electronic address: Geert.LerouxRoels@UGent.be. 2. Centre for the Evaluation of Vaccination, University of Antwerp, Campus Drie Eiken, Universiteitsplein 1, 2610 Antwerp, Belgium. Electronic address: pierre.vandamme@uantwerpen.be. 3. SGS Life Sciences Services, Lange Beeldekensstraat 267, 2060 Antwerp, Belgium. Electronic address: wouter.haazen1@telenet.be. 4. University of Adelaide, Mail Delivery Point 22, Royal Adelaide Hospital, North Terrace, 5000 Adelaide, Australia. Electronic address: sepehr.shakib@sa.gov.au. 5. GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: magalie.caubet@gsk.com. 6. GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: emmanuel.x.aris@gsk.com. 7. GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: jeanne-marie.devaster@gsk.com. 8. GSK Vaccines, Rue de l'Institut 89, 1330 Rixensart, Belgium. Electronic address: Mathieu.peeters@yahoo.co.uk.
Abstract
BACKGROUND: Non-typeable Haemophilus influenzae (NTHi) is a major cause of various respiratory diseases. The development of an effective vaccine against NTHi mandates new approaches beyond conjugated vaccines as this opportunistic bacterium is non-encapsulated. Here we report on the safety, reactogenicity and immunogenicity of a multi-component investigational vaccine based on three conserved surface proteins from NTHi (proteins D [PD], E [PE] and Pilin A [PilA]) in two observer-blind phase I studies. METHODS: In the first study (NCT01657526), 48 healthy 18-40 year-olds received twovaccine formulations (10 or 30μg of each antigen [PD and a fusion protein PE-PilA]) or saline placebo at months 0 and 2. In the second study (NCT01678677), 270 50-70 year-olds, current or former smokers, received eightvaccine formulations (10 or 30μg antigen/dose non-adjuvanted or adjuvanted with alum, AS01E or AS04C) or saline placebo at months 0, 2 and 6 (plain and alum-adjuvanted groups) and at months 0 and 2 (AS-adjuvanted groups). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the studies. Humoral and antigen-specific T-cell immunity (in study 2 only) responses were assessed up to 12 months post-vaccination. RESULTS:Observed reactogenicity was highest in the AS-adjuvanted groups but no safety concerns were identified with any of the NTHi vaccine formulations. One fatal SAE (cardiac arrest) not considered related to vaccination, and one pIMD (non-serious psoriasis) in the Placebo group, were reported post-dose 3 in Study 2. All formulations generated a robust antibody response while the AS01-adjuvanted formulations produced the highest humoral and cellular immune responses. CONCLUSION: This study confirms that the NTHi vaccine formulations had an acceptable reactogenicity and safety profile and were immunogenic in adults. These results justify further clinical development of this NTHi vaccine candidate.
RCT Entities:
BACKGROUND: Non-typeable Haemophilus influenzae (NTHi) is a major cause of various respiratory diseases. The development of an effective vaccine against NTHi mandates new approaches beyond conjugated vaccines as this opportunistic bacterium is non-encapsulated. Here we report on the safety, reactogenicity and immunogenicity of a multi-component investigational vaccine based on three conserved surface proteins from NTHi (proteins D [PD], E [PE] and Pilin A [PilA]) in two observer-blind phase I studies. METHODS: In the first study (NCT01657526), 48 healthy 18-40 year-olds received two vaccine formulations (10 or 30μg of each antigen [PD and a fusion protein PE-PilA]) or saline placebo at months 0 and 2. In the second study (NCT01678677), 270 50-70 year-olds, current or former smokers, received eight vaccine formulations (10 or 30μg antigen/dose non-adjuvanted or adjuvanted with alum, AS01E or AS04C) or saline placebo at months 0, 2 and 6 (plain and alum-adjuvanted groups) and at months 0 and 2 (AS-adjuvanted groups). Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) throughout the studies. Humoral and antigen-specific T-cell immunity (in study 2 only) responses were assessed up to 12 months post-vaccination. RESULTS: Observed reactogenicity was highest in the AS-adjuvanted groups but no safety concerns were identified with any of the NTHi vaccine formulations. One fatal SAE (cardiac arrest) not considered related to vaccination, and one pIMD (non-serious psoriasis) in the Placebo group, were reported post-dose 3 in Study 2. All formulations generated a robust antibody response while the AS01-adjuvanted formulations produced the highest humoral and cellular immune responses. CONCLUSION: This study confirms that the NTHi vaccine formulations had an acceptable reactogenicity and safety profile and were immunogenic in adults. These results justify further clinical development of this NTHi vaccine candidate.
Authors: Mark R Alderson; Tim Murphy; Stephen I Pelton; Laura A Novotny; Laura L Hammitt; Arwa Kurabi; Jian-Dong Li; Ruth B Thornton; Lea-Ann S Kirkham Journal: Int J Pediatr Otorhinolaryngol Date: 2019-12-18 Impact factor: 1.675
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Authors: Sara Russo Krauss; Marija Barbateskovic; Sarah Louise Klingenberg; Snezana Djurisic; Sesilje Bondo Petersen; Mette Kenfelt; De Zhao Kong; Janus C Jakobsen; Christian Gluud Journal: BMJ Open Date: 2022-06-23 Impact factor: 3.006