Rationale: Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently required. Objectives: Here, we report the safety and immunogenicity of a novel mucosal RSV F protein vaccine linked to an immunostimulatory bacterium-like particle (BLP). Methods: In this phase I, randomized, double-blind, placebo-controlled trial, 48 healthy volunteers, aged 18-49 years, were randomly assigned to receive placebo or SynGEM (low or high dose) intranasally by prime-boost administration. The primary outcome was safety and tolerability, with secondary objectives assessing virus-specific immunogenicity.Measurements and Main Results: There were no significant differences in adverse events between placebo and vaccinated groups. SynGEM induced systemic plasmablast responses and significant, durable increases in RSV-specific serum antibody in healthy, seropositive adults. Volunteers given low-dose SynGEM (140 μg F, 2 mg BLP) required a boost at Day 28 to achieve plateau responses with a maximum fold change of 2.4, whereas high-dose recipients (350 μg F, 5 mg BLP) achieved plateau responses with a fold change of 1.5 after first vaccination that remained elevated up to 180 days after vaccination, irrespective of further boosting. Palivizumab-like antibodies were consistently induced, but F protein site ∅-specific antibodies were not detected, and virus-specific nasal IgA responses were heterogeneous, with the strongest responses in individuals with lower pre-existing antibody levels.Conclusions: SynGEM is thus the first nonreplicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers.Clinical trials registered with www.clinicaltrials.gov (NCT02958540).
Rationale: Needle-free intranasal vaccines offer major potential advantages, especially against pathogens entering via mucosal surfaces. As yet, there is no effective vaccine against respiratory syncytial virus (RSV), a ubiquitous pathogen of global importance that preferentially infects respiratory epithelial cells; new strategies are urgently required. Objectives: Here, we report the safety and immunogenicity of a novel mucosal RSV F protein vaccine linked to an immunostimulatory bacterium-like particle (BLP). Methods: In this phase I, randomized, double-blind, placebo-controlled trial, 48 healthy volunteers, aged 18-49 years, were randomly assigned to receive placebo or SynGEM (low or high dose) intranasally by prime-boost administration. The primary outcome was safety and tolerability, with secondary objectives assessing virus-specific immunogenicity.Measurements and Main Results: There were no significant differences in adverse events between placebo and vaccinated groups. SynGEM induced systemic plasmablast responses and significant, durable increases in RSV-specific serum antibody in healthy, seropositive adults. Volunteers given low-dose SynGEM (140 μg F, 2 mg BLP) required a boost at Day 28 to achieve plateau responses with a maximum fold change of 2.4, whereas high-dose recipients (350 μg F, 5 mg BLP) achieved plateau responses with a fold change of 1.5 after first vaccination that remained elevated up to 180 days after vaccination, irrespective of further boosting. Palivizumab-like antibodies were consistently induced, but F protein site ∅-specific antibodies were not detected, and virus-specific nasal IgA responses were heterogeneous, with the strongest responses in individuals with lower pre-existing antibody levels.Conclusions: SynGEM is thus the first nonreplicating intranasal RSV subunit vaccine to induce persistent antibody responses in human volunteers.Clinical trials registered with www.clinicaltrials.gov (NCT02958540).
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Authors: Ruth A Karron; Cindy Luongo; Bhagvanji Thumar; Karen M Loehr; Janet A Englund; Peter L Collins; Ursula J Buchholz Journal: Sci Transl Med Date: 2015-11-04 Impact factor: 17.956
Authors: C Gray; M S Ahmed; A Mubarak; A V Kasbekar; S Derbyshire; M S McCormick; M K Mughal; P S McNamara; T Mitchell; Q Zhang Journal: Mucosal Immunol Date: 2013-11-13 Impact factor: 7.313
Authors: Nienke M Scheltema; Angela Gentile; Florencia Lucion; D James Nokes; Patrick K Munywoki; Shabir A Madhi; Michelle J Groome; Cheryl Cohen; Jocelyn Moyes; Kentigern Thorburn; Somsak Thamthitiwat; Hitoshi Oshitani; Socorro P Lupisan; Aubree Gordon; José F Sánchez; Katherine L O'Brien; Bradford D Gessner; Agustinus Sutanto; Asuncion Mejias; Octavio Ramilo; Najwa Khuri-Bulos; Natasha Halasa; Fernanda de-Paris; Márcia Rosane Pires; Michael C Spaeder; Bosco A Paes; Eric A F Simões; Ting F Leung; Maria Tereza da Costa Oliveira; Carla Cecília de Freitas Lázaro Emediato; Quique Bassat; Warwick Butt; Hsin Chi; Uzma Bashir Aamir; Asad Ali; Marilla G Lucero; Rodrigo A Fasce; Olga Lopez; Barbara A Rath; Fernando P Polack; Jesse Papenburg; Srđan Roglić; Hisato Ito; Edward A Goka; Diederick E Grobbee; Harish Nair; Louis J Bont Journal: Lancet Glob Health Date: 2017-10 Impact factor: 26.763
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