A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation

Stobart, Christopher C.; Rostad, Christina A.; Ke, Zunlong; Dillard, Rebecca S.; Hampton, Cheri M.; Strauss, J; Yi, Hong; Hotard, Anne L.; Meng, Jia; Pickles, Raymond J.; Sakamoto, Kaori; Lee, Sujin; Currier, Michael G.; Moin, Syed M.; Graham, Barney S.; Boukhvalova, Marina S.; Gilbert, Brian E.; Blanco, Jorge C. G.; Piedra, Pedro A.; Wright, Elizabeth; Moore, Martin L.

doi:10.1038/ncomms13916

Cited by 82 publications

(92 citation statements)

References 56 publications

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“…The only vaccine approaches proven to not induce enhanced disease are live-attenuated or live chimeric virus vaccines [36]. Recent advances in the development of vaccines within this category that either improve immunogenicity despite greater vaccine virus attenuation [37,38], improve manufacturing capacity [39], or improve stability of surface proteins and immunogenicity [38,40,41] will provide potential solutions for immunizing the antigen-naïve infant. Other approaches that deliver vaccine antigens through gene-based vectors [42–44] or nucleic acid [45,46] are another possible avenue towards the goal of infant immunization.…”

Section: Vaccine Approaches To Protect Infantsmentioning

confidence: 99%

Vaccine development for respiratory syncytial virus

Graham

2017

Current Opinion in Virology

136

106

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Respiratory syncytial virus (RSV) is an important and ubiquitous respiratory pathogen for which no vaccine is available notwithstanding more than 50 years of effort. It causes the most severe disease at the extremes of age and in settings of immunodeficiency. Although RSV is susceptible to neutralizing antibody, it has evolved multiple mechanisms of immune evasion allowing it to repeatedly infect people despite relatively little genetic diversity. Recent breakthroughs in determining the structure and antigenic content of the fusion (F) glycoprotein in its metastable untriggered prefusion form (pre-F) and the stable rearranged postfusion form (post-F) have yielded vaccine strategies that can induce potent neutralizing antibody responses and effectively boost pre-existing neutralizing activity. In parallel, novel live-attenuated and chimeric virus vaccine candidates and other novel approaches to deliver vaccine antigens have been developed. These events and activities have aroused optimism and a robust pipeline of potential vaccine products that promise to provide a means to reduce the public health burden of RSV infection.

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Section: Vaccine Approaches To Protect Infantsmentioning

confidence: 99%

Vaccine development for respiratory syncytial virus

Graham

2017

Current Opinion in Virology

136

106

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“…The underlining mechanism cannot be explained as the overall number of subjects enrolled in this study was low, and there was no vaccine-associated virus recovered from these subjects. Other ΔSH vaccine candidates include OE4 (RSV-A2-dNS1-dNS2-ΔSH-dGm-Gsnull-line19F) and DB1 (RSV-A2-dNS-ΔSH-BAF), which have both been found to be immunogenic in cotton rats [39,40]. …”

Section: Live-attenuated Vaccinesmentioning

confidence: 99%

Ongoing developments in RSV prophylaxis: a clinician’s analysis

Rezaee

Linfield

Harford

et al. 2017

Current Opinion in Virology

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Respiratory syncytial virus (RSV) is the most common respiratory pathogen in infants and young children worldwide. Lower respiratory tract infection due to RSV is one of the most common causes of hospitalization for infants, especially those born premature or with chronic lung or heart disease. Furthermore, RSV infection is an important cause of morbidity in adults, particularly in the elderly and immunocompromised individuals. The acute phase of this infection is often followed by episodes of wheezing that recur for months or years and usually lead to a physician diagnosis of asthma. RSV was discovered more than 50 years ago, and despite extensive research to identify pharmacological therapies, the most effective management of this infection remains supportive care. The trial of a formalin-inactivated RSV vaccine in the 1960s resulted in priming the severe illness upon natural infection. Currently, Palivizumab is the only available option for RSV prophylaxis, and because of restricted clinical benefits and high costs, it has been limited to a group of high-risk infants. There are several ongoing trials in preclinical, Phase-I, -II, or -III clinical stages for RSV vaccine development based on various strategies. Here we review the existing available prophylactic options, the current stages of RSV vaccine clinical trials, different strategies, and major hurdles in the development of an effective RSV vaccine.

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“…Further, attenuating NS2 gene deletion has been explored as a strategy to develop a live attenuated RSV vaccine [110], which is currently in phase I clinical evaluation. Likewise, codon-reoptimization of NS1, NS2 and G, together with the deletion of SH proteins led to the generation of a stable attenuated hRSV vaccine, known as OE4 [134], which showed protection and lack of disease enhancement in mice and cotton rats [134]. …”

Section: Prophylaxis Against Hrsv Infectionmentioning

confidence: 99%

Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia—Implications for Vaccine Design

Rey-Jurado

Kalergis

2017

IJMS

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The human respiratory syncytial virus (hRSV) is the causative agent for high rates of hospitalizations due to viral bronchiolitis and pneumonia worldwide. Such a disease is characterized by an infection of epithelial cells of the distal airways that leads to inflammation and subsequently to respiratory failure. Upon infection, different pattern recognition receptors recognize the virus and trigger the innate immune response against the hRSV. Further, T cell immunity plays an important role for virus clearance. Based on animal studies, it is thought that the host immune response to hRSV is based on a biased T helper (Th)-2 and Th17 T cell responses with the recruitment of T cells, neutrophils and eosinophils to the lung, causing inflammation and tissue damage. In contrast, human immunity against RSV has been shown to be more complex with no definitive T cell polarization profile. Nowadays, only a humanized monoclonal antibody, known as palivizumab, is available to protect against hRSV infection in high-risk infants. However, such treatment involves several injections at a significantly high cost. For these reasons, intense research has been focused on finding novel vaccines or therapies to prevent hRSV infection in the population. Here, we comprehensively review the recent literature relative to the immunological features during hRSV infection, as well as the new insights into preventing the disease caused by this virus.

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A live RSV vaccine with engineered thermostability is immunogenic in cotton rats despite high attenuation

Cited by 82 publications

References 56 publications

Vaccine development for respiratory syncytial virus

Vaccine development for respiratory syncytial virus

Ongoing developments in RSV prophylaxis: a clinician’s analysis

Immunological Features of Respiratory Syncytial Virus-Caused Pneumonia—Implications for Vaccine Design

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