Pre-fusion RSV F strongly boosts pre-fusion specific neutralizing responses in cattle pre-exposed to bovine RSV

Steff, Ann‐Muriel; Monroe, James E.; Friedrich, Kristian; Chandramouli, Sumana; Nguyên, Thi Lien-Anh; Tian, Sai; Vandepaer, Sarah; Toussaint, Jean‐François; Carfı́, Andrea

doi:10.1038/s41467-017-01092-4

Cited by 31 publications

(42 citation statements)

References 53 publications

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“…Similar to observations in small animal models, vaccination of calves with the pre-F form induced >100 higher neutralization titers compared to the post-F. After bRSV challenge, pre-F immunization conferred superior protection against clinical signs, pulmonary inflammation and reduced bRSV replication in both the upper and lower respiratory tract [93]. Moreover, in bRSV seropositive animals a single administration of non-adjuvanted pre-F form markedly boosted pre-existing bRSV neutralizing responses and pre-F specific neutralizing antibodies, while post-F did not [94]. Therefore, pre-F represents a promising candidate for further increasing neutralizing antibodies in pre-exposed populations.…”

Section: Adaptive Immune Responsementioning

confidence: 99%

Utility of the Neonatal Calf Model for Testing Vaccines and Intervention Strategies for Use against Human RSV Infection

et al. 2019

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Respiratory syncytial virus (RSV) is a significant cause of pediatric respiratory tract infections. It is estimated that two-thirds of infants are infected with RSV during the first year of life and it is one of the leading causes of death in this age group worldwide. Similarly, bovine RSV is a primary viral pathogen in cases of pneumonia in young calves and plays a significant role in bovine respiratory disease complex. Importantly, naturally occurring infection of calves with bovine RSV shares many features in common with human RSV infection. Herein, we update our current understanding of RSV infection in cattle, with particular focus on similarities between the calf and human infection, and the recent reports in which the neonatal calf has been employed for the development and testing of vaccines and therapeutics which may be applied to hRSV infection in humans.

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Section: Adaptive Immune Responsementioning

confidence: 99%

Utility of the Neonatal Calf Model for Testing Vaccines and Intervention Strategies for Use against Human RSV Infection

et al. 2019

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“…A variety of animal models exist to research respiratory viruses such as influenza [124][125][126], RSV [127][128][129][130][131][132][133][134][135][136][137], HRV [22,[138][139][140]. No single animal offers a platform for all respiratory viruses that infect humans, and different animal models exist for the same virus, which can give different, often conflicting results.…”

Section: The History Of the Human Viral Challenge Modelmentioning

confidence: 99%

The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

et al. 2018

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The Human Viral Challenge (HVC) model has, for many decades, helped in the understanding of respiratory viruses and their role in disease pathogenesis. In a controlled setting using small numbers of volunteers removed from community exposure to other infections, this experimental model enables proof of concept work to be undertaken on novel therapeutics, including vaccines, immunomodulators and antivirals, as well as new diagnostics.Crucially, unlike conventional phase 1 studies, challenge studies include evaluable efficacy endpoints that then guide decisions on how to optimise subsequent field studies, as recommended by the FDA and thus licensing studies that follow. Such a strategy optimises the benefit of the studies and identifies possible threats early on, minimising the risk to subsequent volunteers but also maximising the benefit of scarce resources available to the research group investing in the research. Inspired by the principles of the 3Rs (Replacement, Reduction and Refinement) now commonly applied in the preclinical phase, HVC studies allow refinement and reduction of the subsequent development phase, accelerating progress towards further statistically powered phase 2b studies. The breadth of data generated from challenge studies allows for exploration of a wide range of variables and endpoints that can then be taken through to pivotal phase 3 studies.We describe the disease burden for acute respiratory viral infections for which current conventional development strategies have failed to produce therapeutics that meet clinical need. The Authors describe the HVC model’s utility in increasing scientific understanding and in progressing promising therapeutics through development.The contribution of the model to the elucidation of the virus-host interaction, both regarding viral pathogenicity and the body’s immunological response is discussed, along with its utility to assist in the development of novel diagnostics.Future applications of the model are also explored.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0784-1) contains supplementary material, which is available to authorized users.

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“…This prediction has been borne out in multiple studies of DS-Cav1, a prefusion-stabilized F antigen that has elicited significantly higher neutralizing antibody titers than postfusion F in naive mice and nonhuman primates (McLellan et al., 2013b) and bovine RSV-primed cattle (Steff et al., 2017) and is now in Phase I clinical trials (NCT03049488). Additional engineered prefusion RSV F antigens have shown similar improvements in eliciting neutralizing antibody responses and in some cases, exhibit improved physical and antigenic stability relative to DS-Cav1 (Joyce et al., 2016, Krarup et al., 2015, Palomo et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus

Marcandalli

Fiala

Ols

et al. 2019

Cell

373

405

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SummaryRespiratory syncytial virus (RSV) is a worldwide public health concern for which no vaccine is available. Elucidation of the prefusion structure of the RSV F glycoprotein and its identification as the main target of neutralizing antibodies have provided new opportunities for development of an effective vaccine. Here, we describe the structure-based design of a self-assembling protein nanoparticle presenting a prefusion-stabilized variant of the F glycoprotein trimer (DS-Cav1) in a repetitive array on the nanoparticle exterior. The two-component nature of the nanoparticle scaffold enabled the production of highly ordered, monodisperse immunogens that display DS-Cav1 at controllable density. In mice and nonhuman primates, the full-valency nanoparticle immunogen displaying 20 DS-Cav1 trimers induced neutralizing antibody responses ∼10-fold higher than trimeric DS-Cav1. These results motivate continued development of this promising nanoparticle RSV vaccine candidate and establish computationally designed two-component nanoparticles as a robust and customizable platform for structure-based vaccine design.

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Pre-fusion RSV F strongly boosts pre-fusion specific neutralizing responses in cattle pre-exposed to bovine RSV

Cited by 31 publications

References 53 publications

Utility of the Neonatal Calf Model for Testing Vaccines and Intervention Strategies for Use against Human RSV Infection

Utility of the Neonatal Calf Model for Testing Vaccines and Intervention Strategies for Use against Human RSV Infection

The human viral challenge model: accelerating the evaluation of respiratory antivirals, vaccines and novel diagnostics

Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus

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