Dataset Information

Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants.

ABSTRACT:

Background

Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory infection (MARI).

Methods

We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatient lower respiratory tract infection (LRTI).

Results

There were no significant differences between primary endpoint rates (8.1%, placebo; 7.7%, 1-dose; 9.3%, 2-dose). Suptavumab prevented RSV A infections (relative risks, .38; 95% confidence interval [CI], .14-1.05 in the 1-dose group and .39 [95% CI, .14-1.07] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .0499), while increasing the rate of RSV B infections (relative risk 1.36 [95% CI, .73-2.56] in the 1-dose group and 1.69 [95% CI, .92-3.08] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .12). Sequenced RSV isolates demonstrated no suptavumab epitope changes in RSV A isolates, while all RSV B isolates had 2-amino acid substitution in the suptavumab epitope that led to loss of neutralization activity. Treatment emergent adverse events were balanced across treatment groups.

Conclusions

Suptavumab did not reduce overall RSV hospitalizations or outpatient LRTI because of a newly circulating mutant strain of RSV B. Genetic variation in circulating RSV strains will continue to challenge prevention efforts.

Clinical trials registration

NCT02325791.

SUBMITTER: Simoes EAF

PROVIDER: S-EPMC8653633 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants.

Simões Eric A F EAF Forleo-Neto Eduardo E Geba Gregory P GP Kamal Mohamed M Yang Feng F Cicirello Helen H Houghton Matthew R MR Rideman Ronald R Zhao Qiong Q Benvin Sarah L SL Hawes Alicia A Fuller Erin D ED Wloga Elzbieta E Pizarro Jose M Novoa JMN Munoz Flor M FM Rush Scott A SA McLellan Jason S JS Lipsich Leah L Stahl Neil N Yancopoulos George D GD Weinreich David M DM Kyratsous Christos A CA Sivapalasingam Sumathi S

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20211201 11

<h4>Background</h4>Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory infection (MARI).<h4>Methods</h4>We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatie ...[more]

PMID: 32897368

Similar Datasets

Project description:BackgroundPalivizumab, a monoclonal antibody and the only licensed immunization product for preventing respiratory syncytial virus (RSV) infection, is recommended for children with certain high-risk conditions. Other antibody products and maternal vaccines targeting young infants are in clinical development. Few studies have compared products closest to potential licensure and have primarily focused on the effects on hospitalizations only. Estimates of the impact of these products on medically-attended (MA) infections in a variety of healthcare settings are needed to assist with developing RSV immunization recommendations.MethodsWe developed a tool for practicing public health officials to estimate the impact of immunization strategies on RSV-associated MA lower respiratory tract infections (LRTIs) in various healthcare settings among infants <12 months. Users input RSV burden and seasonality and examine the influence of altering product efficacy and uptake assumptions. We used the tool to evaluate candidate products' impacts among a US birth cohort.ResultsWe estimated without immunization, 407,360 (range: 339,650-475,980) LRTIs are attended annually in outpatient clinics, 147,240 (126,070-168,510) in emergency departments (EDs), and 33,180 (24,760-42,900) in hospitals. A passive antibody candidate targeting all infants prevented the most LRTIs: 196,470 (48% of visits without immunization) outpatient clinic visits (range: 163,810-229,650), 75,250 (51%) EDs visits (64,430-86,090), and 18,140 (55%) hospitalizations (13,770-23,160). A strategy combining maternal vaccine candidate and palivizumab prevented 58,210 (14% of visits without immunization) LRTIs in outpatient clinics (range: 48,520-67,970), 19,580 (13%) in EDs (16,760-22,400), and 8,190 (25%) hospitalizations (6,390-10,150).ConclusionsResults underscore the potential for anticipated products to reduce serious RSV illness. Our tool (provided to readers) can be used by different jurisdictions and accept updated data. Results can aid economic evaluations and public health decision-making regarding RSV immunization products.

Project description:BackgroundPreterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection.MethodsThree datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out.ResultsTotally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p = 0.041), more requirements of mechanical ventilation (p = 0.034), more frequent hospitalization (p < 0.001) and longer cumulative hospital stay (p = 0.012).ConclusionIFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.

Dataset Information

Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants.

Background

Methods

Results

Conclusions

Clinical trials registration

Publications

Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets