Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults

Walsh, Edward E.; Marc, Gonzalo Pérez; Zareba, Agnieszka M; Falsey, Ann R.; Jiang, Qin; Patton, Michael Quinn; Polack, Fernando P.; Llapur, Conrado J.; Doreski, Pablo A; Ilangovan, Kumar; Rämet, Mika; Fukushima, Yasushi; Hussen, Nazreen; Bont, Louis; Cardona, Jose F; DeHaan, Elliot; Villa, Giselle Castillo; Ingilizova, Marinela; Eiras, Daniel P.; Mikati, Tarek; Shah, Rupal N; Schneider, Katherine; Cooper, David A.; Koury, Kenneth; Lino, Maria-Maddalena; Anderson, Annaliesa S.; Jansen, Kathrin U.; Swanson, Kena A.; Gurtman, Alejandra; Gruber, William C.; Schmöele-Thoma, Beate

doi:10.1056/nejmoa2213836

Cited by 276 publications

(180 citation statements)

References 35 publications

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“…RSVpreF has demonstrated efficacy against symptomatic RSV infection in a human challenge study (39), and it has been advanced to global, pivotal phase 3 efficacy trials in pregnant women and their infants (NCT04424316) and older adults (NCT05035212) (40). Both studies met their primary efficacy endpoint, confirming the ability of RSVpreF to protect young infants by maternal immunization and older adults by active immunization (41,42).…”

Section: Discussionmentioning

confidence: 90%

Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine

et al. 2023

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Respiratory syncytial virus (RSV) is the leading, global cause of serious respiratory disease in infants and is an important cause of respiratory illness in older adults. No RSV vaccine is currently available. The RSV fusion (F) glycoprotein is a key antigen for vaccine development, and its prefusion conformation is the target of the most potent neutralizing antibodies. Here, we describe a computational and experimental strategy for designing immunogens that enhance the conformational stability and immunogenicity of RSV prefusion F. We obtained an optimized vaccine antigen after screening nearly 400 engineered F constructs. Through in vitro and in vivo characterization studies, we identified F constructs that are more stable in the prefusion conformation and elicit ~10-fold higher serum neutralizing titers in cotton rats than DS-Cav1. The stabilizing mutations of the lead construct (847) were introduced onto F glycoprotein backbones of strains representing the dominant circulating genotypes of the two major RSV subgroups, A and B. Immunization of cotton rats with a bivalent vaccine formulation of these antigens conferred complete protection against RSV challenge, with no evidence of disease enhancement. The resulting bivalent RSV prefusion F investigational vaccine has recently been shown to be efficacious against RSV disease in two pivotal phase 3 efficacy trials, one for passive protection of infants by immunization of pregnant women and the second for active protection of older adults by direct immunization.

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Section: Discussionmentioning

confidence: 90%

Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine

et al. 2023

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“…GSK’s RSV vaccine for older people looks likely to be the first to be approved, but others may not be far behind. Interim results from Pfizer’s ongoing phase 3 trial that were recently published in the New England Journal of Medicine showed a vaccine efficacy of 85.7% 4. Moderna has an mRNA vaccine candidate and in January said that it was submitting for regulatory approval, after the results of a placebo controlled study of 37 000 adults demonstrated efficacy of 83.7% against RSV lower respiratory tract disease 5…”

Section: Other Vaccinesmentioning

confidence: 99%

First RSV vaccine for older adults is approved in Europe

Wise¹

2023

BMJ

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“…Systemic ribavirin could be considered in HCT recipients with RSV URTI with a higher risk of progression [2,34 & ], given the high cost of aerosolized ribavirin [35] and lack of development of other antivirals [36,37]. In 2023, the U.S. Food and Drug Administration (FDA) approved a RSV prefusion F protein vaccine for the elderly, and it is anticipated the RSV vaccine will be approved for pregnant women to protect newborns [38,39]. Similarly, the FDA recently approved nirsevimab, a single-dose long-acting monoclonal antibody targeting prefusion F protein, based on the results of a recent randomized controlled trial [40,41].…”

Section: Risk For Severity In Respiratory Synctial Virusmentioning

confidence: 99%

Risk factors for severity in seasonal respiratory viral infections and how they guide management in hematopoietic cell transplant recipients

Matsui,

Ogimi

2023

Current Opinion in Infectious Diseases

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Purpose of review Seasonal respiratory virus infections (RVIs) often progress to severe diseases in hematopoietic cell transplant (HCT) recipients. This review summarizes the current evidence on risk factors for the severity of RVIs in this high-risk population and provides clinical management. Recent findings The likelihood of the respiratory viral disease progression depends on the immune status of the host and the type of virus. Conventional host factors, such as the immunodeficiency scoring index and the severe immunodeficiency criteria, have been utilized to estimate the risk of progression to severe disease, including mortality. Recent reports have suggested nonconventional risk factors, such as hyperglycemia, hypoalbuminemia, prior use of antibiotics with broad anaerobic activity, posttransplant cyclophosphamide, and pulmonary impairment after RVIs. Identifying novel and modifiable risk factors is important with the advances of novel therapeutic and preventive interventions for RVIs. Summary Validation of recently identified risk factors for severe RVIs in HCT recipients is required. The development of innovative interventions along with appropriate risk stratification is critical to improve outcomes in this vulnerable population.

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Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults

Cited by 276 publications

References 35 publications

Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine

Rational design of a highly immunogenic prefusion-stabilized F glycoprotein antigen for a respiratory syncytial virus vaccine

First RSV vaccine for older adults is approved in Europe

Risk factors for severity in seasonal respiratory viral infections and how they guide management in hematopoietic cell transplant recipients

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