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

Glenn, Gregory M.; Smith, Gale; Fries, Louis; Raghunandan, Rama; Lü, Huanzhang; Zhou, Bin; Thomas, D. Nigel; Hickman, Somia P.; Kpamegan, Eloi; Boddapati, Sarathi; Piedra, Pedro A.

doi:10.1016/j.vaccine.2012.11.009

Cited by 126 publications

(64 citation statements)

References 33 publications

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“…156 F protein virallike particle vaccines administered during the latter half of pregnancy might offer passive protection for young children through the first months of life. 157 …”

Section: Future Possibilitiesmentioning

confidence: 99%

Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection

Brady¹,

Byington²,

Davies³

et al. 2014

Pediatrics

305

170

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Guidance from the American Academy of Pediatrics (AAP) for the use of palivizumab prophylaxis against respiratory syncytial virus (RSV) was first published in a policy statement in 1998. Guidance initially was based on the result from a single randomized, placebo-controlled clinical trial conducted in 1996–1997 describing an overall reduction in RSV hospitalization rate from 10.6% among placebo recipients to 4.8% among children who received prophylaxis. The results of a second randomized, placebo-controlled trial of children with hemodynamically significant heart disease were published in 2003 and revealed a reduction in RSV hospitalization rate from 9.7% in control subjects to 5.3% among prophylaxis recipients. Because no additional controlled trials regarding efficacy were published, AAP guidance has been updated periodically to reflect the most recent literature regarding children at greatest risk of severe disease. Since the last update in 2012, new data have become available regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effects of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, and the effect of prophylaxis on wheezing and palivizumab-resistant RSV isolates. These data enable further refinement of AAP guidance to most clearly focus on those children at greatest risk.

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“…156 F protein virallike particle vaccines administered during the latter half of pregnancy might offer passive protection for young children through the first months of life. 157 …”

Section: Future Possibilitiesmentioning

confidence: 99%

Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection

Brady¹,

Byington²,

Davies³

et al. 2014

Pediatrics

305

170

View full text Add to dashboard Cite

show abstract

“…These products have been tested in healthy RSV-seropositive adults, but most of the data are not yet publically available. Only data from the Novavax rosetted F subunit have been published and show that, at the highest reported dose level of 60 mcg, there is about a 2-fold rise in NT activity and about a 10-fold rise in binding antibody to F (24). …”

Section: Rsv F (Fusion) Glycoproteinmentioning

confidence: 99%

Novel antigens for RSV vaccines

Graham

Modjarrad

McLellan

2015

Current Opinion in Immunology

106

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Respiratory syncytial virus (RSV) remains a leading global cause of infant mortality and adult morbidity. Infection, which recurs throughout life, elicits only short-lived immunity. The development of a safe and efficacious vaccine has, thus far, been elusive. Recent technological advances, however, have yielded promising RSV vaccine candidates that are based on solving atomic-level structures of surface glycoproteins interacting with neutralizing antibodies. The class I fusion glycoprotein, F, serves as the primary antigenic component of most vaccines, and is the target of the only licensed monoclonal antibody product used to reduce the frequency of severe disease in high-risk neonates. However, success of prior F-based vaccines has been limited by the lack of understanding how the conformational rearrangement between a metastable prefusion F (pre-F) and a stable postfusion F (post-F) affected the epitope content. Neutralizing epitopes reside on both conformations, but those specific to pre-F are far more potent than those previously identified and present on post-F. The solution of the pre-F structure and its subsequent characterization and stabilization illustrates the value of a structure-based approach to vaccine development, and provides hope that a safe and effective RSV vaccine is possible.

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“…The vast majority of the reports of tests of vaccine potential concern heterologous VLPs or nanoparticles carrying the hRSV F and/or G protein, in part because these systems are established or efficient and because hRSV particle assembly is poorly understood. The heterologous systems include Newcastle disease virus-, Sendai virus-, or baculovirus-based VLPs; nanoparticles; and gold-based nanorods and have shown encouraging results in the BALB/c mouse model (6)(7)(8)(9)(10)(11)(12) and humans (13,14). In comparison, authentic hRSV VLPs structurally resemble wild-type (wt) virions and also incorporate some of the internal hRSV proteins (5), features that may be advantageous for vaccine purposes.…”

mentioning

confidence: 99%

The Respiratory Syncytial Virus Phosphoprotein, Matrix Protein, and Fusion Protein Carboxy-Terminal Domain Drive Efficient Filamentous Virus-Like Particle Formation

Meshram

Baviskar

Ognibene

et al. 2016

J Virol

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Virus-like particles (VLPs) are attractive as a vaccine concept. For human respiratory syncytial virus (hRSV), VLP assembly is poorly understood and appears inefficient. Hence, hRSV antigens are often incorporated into foreign VLP systems to generate anti-RSV vaccine candidates. To better understand the assembly, and ultimately to enable efficient production, of authentic hRSV VLPs, we examined the associated requirements and mechanisms. In a previous analysis in HEp-2 cells, the nucleoprotein (N), phosphoprotein (P), matrix protein (M), and fusion protein (F) were required for formation of filamentous VLPs, which, similar to those of wild-type virus, were associated with the cell surface. Using fluorescence and electron microscopy combined with immunogold labeling, we examined the surfaces of transfected HEp-2 cells and further dissected the process of filamentous VLP formation. Our results show that N is not required. Coexpression of P plus M plus F, but not P plus M, M plus F, or P plus F, induced both viral protein coalescence and formation of filamentous VLPs that resembled wild-type virions. Despite suboptimal coalescence in the absence of P, the M and F proteins, when coexpressed, formed cell surface-associated filaments with abnormal morphology, appearing longer and thinner than wild-type virions. For F, only the carboxy terminus (Fstem) was required, and addition of foreign protein sequences to Fstem allowed incorporation into VLPs. Together, the data show that P, M, and the F carboxy terminus are sufficient for robust viral protein coalescence and filamentous VLP formation and suggest that M-F interaction drives viral filament formation, with P acting as a type of cofactor facilitating the process and exerting control over particle morphology. IMPORTANCEhRSV is responsible for >100,000 deaths in children worldwide, and a vaccine is not available. Among the potential anti-hRSV approaches are virus-like particle (VLP) vaccines, which, based on resemblance to virus or viral components, can induce protective immunity. For hRSV, few reports are available concerning authentic VLP production or testing, in large part because VLP production is inefficient and the mechanisms underlying particle assembly are poorly understood. Here, we took advantage of the cell-associated nature of RSV particles and used high-resolution microscopy analyses to examine the viral proteins required for formation of wild-type-virus-resembling VLPs, the contributions of these proteins to morphology, and the domains involved in incorporation of the antigenically important viral F protein. The results provide new insights that will facilitate future production of hRSV VLPs with defined shapes and compositions and may translate into improved manufacture of live-attenuated hRSV vaccines. H uman respiratory syncytial virus (hRSV) is an important viral agent of respiratory tract disease in infants, children, immunosuppressed individuals, and the elderly (1-3). In pursuit of a vaccine to prevent hRSV disease, a virus-like particle (...

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

Cited by 126 publications

References 33 publications

Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection

Updated Guidance for Palivizumab Prophylaxis Among Infants and Young Children at Increased Risk of Hospitalization for Respiratory Syncytial Virus Infection

Novel antigens for RSV vaccines

The Respiratory Syncytial Virus Phosphoprotein, Matrix Protein, and Fusion Protein Carboxy-Terminal Domain Drive Efficient Filamentous Virus-Like Particle Formation

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