Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape

Mazur, Natalie I; Terstappen, Jonne; Baral, Ranju; Bardají, Azucena; Beutels, Philippe; Buchholz, Ursula J.; Cohen, Cheryl; Crowe, James E.; Cutland, Clare; Eckert, Linda O.; Feikin, Daniel R.; Fitzpatrick, Tiffany; Fong, Youyi; Graham, Barney S.; Heikkinen, Terho; Higgins, Deborah; Hirve, Siddhivinayak; Klugman, Keith P.; Kragten-Tabatabaie, Leyla; Lemey, Philippe; Libster, Romina; Löwensteyn, Yvette N; Mejías, Asunción; Muñoz, Flor M.; Munywoki, Patrick K.; Mwananyanda, Lawrence; Nair, Harish; Nunes, Marta C; Ramilo, Octavio; Richmond, Peter; Ruckwardt, Tracy J.; Sande, Charles; Srikantiah, Padmini; Thacker, Naveen; Waldstein, Kody; Weinberger, Dan; Wildenbeest, Joanne G; Wiseman, Dexter J; Zar, Heather J.; Zambon, Maria; Bont, Louis

doi:10.1016/s1473-3099(22)00291-2

Cited by 212 publications

(201 citation statements)

References 81 publications

(96 reference statements)

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“…There are currently a number of paediatric and maternal RSV vaccines approaching clinical translation, with the World Health Organisation predicting vaccine release within 5–10 years 6 and regulatory approval for long‐acting monoclonal antibody prophylaxis expected within 1 year 34 . Important areas for exploration include the development of vaccines for infants <6 months with immunity enduring across childhood and maternal vaccines for transplacental protection 6,32 .…”

Section: Rsv Prevention: Current and Future Interventionsmentioning

confidence: 99%

Respiratory syncytial virus, recurrent wheeze and asthma: A narrative review of pathophysiology, prevention and future directions

Binns

Tuckerman

Licciardi

et al. 2022

J Paediatrics Child Health

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Globally, respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in young children, and the association between severe RSV disease and later recurrent wheeze and asthma is well established. Whilst a causal link between RSV and wheeze/asthma is not yet proven, immunological evidence suggests skewing towards a Th2‐type response, and dampening of IFN‐γ antiviral immunity during RSV infection underpins airway hyper‐reactivity in a subset of susceptible children after RSV infection. Age at primary RSV infection, viral co‐infection and genetic influences may act as effect‐modifiers. Despite the significant morbidity and mortality burden of RSV disease in children, there is currently no licensed vaccine. Recent advancements in RSV preventatives, including long‐acting monoclonal antibodies and maternal vaccinations, show significant promise and we are on the cusp of a new era in RSV prevention. However, the potential impact of RSV preventatives on subsequent wheeze and asthma remains unclear. The ongoing COVID‐19 pandemic and associated public health measures have disrupted the usual seasonality of RSV. Whilst this has posed challenges for health‐care services it has also enhanced our understanding of RSV transmission. The near absence of RSV cases during the first year of the pandemic in the context of strict public health measures has provided a rare opportunity to study the impact of delayed age of primary RSV infection on asthma prevalence. In this review, we summarise current understanding of the association between RSV, recurrent wheeze and asthma with a focus on pathophysiology, preventative strategies and future research priorities.

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Section: Rsv Prevention: Current and Future Interventionsmentioning

confidence: 99%

Respiratory syncytial virus, recurrent wheeze and asthma: A narrative review of pathophysiology, prevention and future directions

Binns

Tuckerman

Licciardi

et al. 2022

J Paediatrics Child Health

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“…Pre-F displays six major antigenic sites (Ø, I, II, III, IV, and V), whereas only four of these sites (I, II, III, and IV) are retained after transition to post-F (10). Before the stabilization of pre-F, many F-based vaccine candidates in clinical testing used post-F as the vaccine antigen, given its high stability; however, no post-F vaccine candidates have advanced to licensure (18,19). The stabilization and structural characterization of pre-F led to the identification of highly neutralization-sensitive epitopes (sites Ø and V) exclusive to the pre-F surface, motivating efforts to use pre-F as a vaccine antigen capable of eliciting high titers of neutralizing antibody (10,11,(20)(21)(22)(23)(24)(25).…”

Section: Introductionmentioning

confidence: 99%

A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine

et al. 2022

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There is currently no licensed vaccine for respiratory syncytial virus (RSV). Here, we assess the effect of RSV fusion protein (F) conformation on B cell responses in a post hoc comparison of samples from the DS-Cav1 [prefusion (pre-F)] and MEDI7510 [postfusion (post-F)] vaccine clinical trials. We compared the magnitude and quality of the serological and B cell responses across time points and vaccines. We measured RSV A and B neutralization, F-binding immunoglobulin G titers, and competition assays at week 0 (before vaccination) and week 4 (after vaccination) to evaluate antibody specificity and potency. To compare B cell specificity and activation, we used pre-F and post-F probes in tandem with a 17-color immunophenotyping flow cytometry panel at week 0 (before vaccination) and week 1 (after vaccination). Our data demonstrate that both DS-Cav1 and MEDI7510 vaccination robustly elicit F-specific antibodies and B cells, but DS-Cav1 elicited antibodies that more potently neutralized both RSV A and B. The superior potency was mediated by antibodies that bind antigenic sites on the apex of pre-F that are not present on post-F. In the memory (CD27 + ) B cell compartment, vaccination with DS-Cav1 or MEDI7510 elicited B cells with different epitope specificities. B cells preferentially binding the pre-F probe were activated in DS-Cav1–vaccinated participants but not in MEDI7510-vaccinated participants. Our findings emphasize the importance of using pre-F as an immunogen in humans because of its deterministic role in eliciting highly potent neutralizing antibodies and memory B cells.

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“…Moreover, RSV, although initially considered to be a virus of infancy only, turned out to be one of the major infective factors in adults, especially in the elderly [ 7 , 8 , 9 ]; despite a limited access to viral testing and often unspecific clinical picture of RSV RTI, the awareness of the significance of RSV is growing [ 10 ]. The high frequency and severity of the RSV disease translate into a huge socioeconomic impact and utilization of healthcare resources seen in paediatric and adult population [ 7 , 11 , 12 , 13 ], urging a development of monoclonal antibodies and vaccines targeting infants, pregnant women and older adults [ 14 ]. A relationship between lower air quality and RSV infections was observed mainly in hospital-based and some community-based studies [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ], with particular interest in PM 2.5 [ 17 , 18 , 21 ], PM 10 [ 15 , 21 ], nitric dioxide (NO 2 ) [ 21 ], ozone [ 22 ], carbon monoxide (CO) [ 20 ], and benzene [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of RSV and Air Pollution Interaction: A Scoping Review

Wrotek

Jackowska

2022

IJMS

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RSV is one of the major infectious agents in paediatrics, and its relationship with air pollution is frequently observed. However, the molecular basis of this interaction is sparsely reported. We sought to systematically review the existing body of literature and identify the knowledge gaps to answer the question: which molecular mechanisms are implied in the air pollutants–RSV interaction? Online databases were searched for original studies published before August 2022 focusing on molecular mechanisms of the interaction. The studies were charted and a narrative synthesis was based upon three expected directions of influence: a facilitated viral entry, an altered viral replication, and an inappropriate host reaction. We identified 25 studies published between 1993 and 2020 (without a noticeable increase in the number of studies) that were performed in human (n = 12), animal (n = 10) or mixed (n = 3) models, and analysed mainly cigarette smoke (n = 11), particulate matter (n = 4), nanoparticles (n = 3), and carbon black (n = 2). The data on a damage to the epithelial barrier supports the hypothesis of facilitated viral entry; one study also reported accelerated viral entry upon an RSV conjugation to particulate matter. Air pollution may result in the predominance of necrosis over apoptosis, and, as an effect, an increased viral load was reported. Similarly, air pollution mitigates epithelium function with decreased IFN-γ and Clara cell secretory protein levels and decreased immune response. Immune response might also be diminished due to a decreased viral uptake by alveolar macrophages and a suppressed function of dendritic cells. On the other hand, an exuberant inflammatory response might be triggered by air pollution and provoke airway hyperresponsiveness (AHR), prolonged lung infiltration, and tissue remodeling, including a formation of emphysema. AHR is mediated mostly by increased IFN-γ and RANTES concentrations, while the risk of emphysema was related to the activation of the IL-17 → MCP-1 → MMP-9 → MMP-12 axis. There is a significant lack of evidence on the molecular basics of the RSV–air pollution interaction, which may present a serious problem with regards to future actions against air pollution effects. The major knowledge gaps concern air pollutants (mostly the influence of cigarette smoke was investigated), the mechanisms facilitating an acute infection or a worse disease course (since it might help plan short-term, especially non-pharmacological, interventions), and the mechanisms of an inadequate response to the infection (which may lead to a prolonged course of an acute infection and long-term sequelae). Thus far, the evidence is insufficient regarding the broadness and complexity of the interaction, and future studies should focus on common mechanisms stimulated by various air pollutants and a comparison of influence of the different contaminants at various concentrations.

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Respiratory syncytial virus prevention within reach: the vaccine and monoclonal antibody landscape

Cited by 212 publications

References 81 publications

Respiratory syncytial virus, recurrent wheeze and asthma: A narrative review of pathophysiology, prevention and future directions

Respiratory syncytial virus, recurrent wheeze and asthma: A narrative review of pathophysiology, prevention and future directions

A prefusion-stabilized RSV F subunit vaccine elicits B cell responses with greater breadth and potency than a postfusion F vaccine

Molecular Mechanisms of RSV and Air Pollution Interaction: A Scoping Review

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