Safety and immunogenicity of a Sf9 insect cell-derived respiratory syncytial virus fusion protein nanoparticle vaccine

被引：123

作者：

Glenn, Gregory M. ^{[1
]}

Smith, Gale ^{[1
]}

Fries, Louis ^{[1
]}

Raghunandan, Rama ^{[1
]}

Lu, Hanxin ^{[1
]}

Zhou, Bin ^{[1
]}

Thomas, D. Nigel ^{[1
]}

Hickman, Somia P. ^{[1
]}

Kpamegan, Eloi ^{[1
]}

Boddapati, Sarathi ^{[1
]}

Piedra, Pedro A. ^{[2
]}

机构：

[1] Novavax Inc, Rockville, MD 20850 USA

[2] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

来源：

VACCINE | 2013年 / 31卷 / 03期

关键词：

Respiratory syncytial virus (RSV); Nanoparticle vaccine; Fusion protein (F protein); Microneutralization; Palivizumab; Competitive ELISA; Anti-F IgG; Aluminum phosphate; SF9 insect cell; NEUTRALIZING ANTIBODY; IMMUNE GLOBULIN; F-GLYCOPROTEIN; INFECTION; RISK; INFLUENZA; HOSPITALIZATIONS; REINFECTION; CHILDREN; INFANTS;

D O I：

10.1016/j.vaccine.2012.11.009

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Objective: We performed a Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate the safety and immunogenicity of a recombinant respiratory syncytial virus (RSV) fusion (F) protein nanoparticle vaccine. Methods: Six formulations with (5, 15,30 and 60 mu g) and without (30 and 6014) aluminum phosphate (AdjuPhos) were administered intramuscularly on day 0 and 30 in a dose escalating fashion to healthy adults 18-49 years of age. Solicited and unsolicited events were collected through day 210. Immunogenicity measures taken at day 0, 30 and 60 included RSV A and B microneutralization, anti-F IgG, antigenic site II peptide and palivizumab competitive antibodies. Results: The vaccine was well-tolerated, with no evident dose-related toxicity or attributable SAEs. At day 60 both RSV A and B microneutralization was significantly increased in vaccinees versus placebo. Across all vaccinees there was a 7- to 19-fold increase in the anti-F IgG and a 7- to 24-fold increase in the antigenic site II binding and palivizumab competitive antibodies. Conclusions: The RSV F nanoparticle vaccine candidate was well tolerated without dose-related increases in adverse events. Measures of immunity indicate that neutralization, anti-RSV F IgG titers and palivizumab competing antibodies were induced at levels that have been associated with decreased risk of hospitalization. NCT01290419. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：524 / 532

页数：9

共 35 条

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