scholarly journals Safety and Tolerability of an Ad26.RSV.preF-based Vaccine in a Phase 2b Study in Older Adults

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1054-1054
Author(s):  
Ann Falsey ◽  
Kristi Williams ◽  
Efi Gymnopoulou ◽  
Stephan Bart ◽  
John Ervin ◽  
...  
Keyword(s):  
Older Adults ◽  
Injection Site ◽  
Vaccine Group ◽  
Double Blind ◽  
Injection Site Reactions ◽  
Lower Respiratory Tract Disease ◽  
Study Population ◽  
Syncytial Virus ◽  
Tract Disease ◽  
Grade 3

Abstract Respiratory syncytial virus (RSV) may cause severe lower respiratory tract disease in older adults and there is currently no approved vaccine. We assessed the safety and reactogenicity of an Ad26.RSV.preF-based vaccine in a randomized, double-blind, placebo-controlled Phase 2b proof-of-concept trial in adults aged ≥65 years (CYPRESS; NCT03982199). Prior to the RSV season, participants were randomized 1:1 to receive an Ad26.RSV.preF-based vaccine or placebo. Solicited adverse events (AEs; fatigue, headache, nausea, myalgia, fever, injection site reactions) and unsolicited AEs were assessed from time of vaccination to Day 8 and Day 29, respectively, in a safety subset of 695 participants (vaccine, n=348; placebo, n=347). All participants were followed for serious AEs (SAEs) until the end of the RSV season or 6 months after vaccination, whichever occurred later. A total of 5728 participants were randomized and received vaccine or placebo (n=2891 in each group). In the safety subset, the frequency of solicited AEs and Grade ≥3 solicited AEs was 51.4% and 3.2% in the vaccine group and 20.2% and 0.6% in the placebo group, respectively. The most frequent solicited AEs in the vaccine group were fatigue, myalgia, headache, and injection site pain/tenderness. The rates of unsolicited AEs and Grade ≥3 unsolicited AEs were similar between the vaccine (16.7% and 1.7%) and placebo (14.4% and 1.4%) groups. In the overall study population, the rate of SAEs was similar between groups (vaccine, 4.6%; placebo, 4.7%); none were considered related to the vaccine. The Ad26.RSV.preF-based vaccine was safe and well tolerated in adults aged ≥65 years.

Ribavirin. Red Book Committee Recommendations Questioned

PEDIATRICS ◽  
1994 ◽  
Vol 93 (4) ◽  
pp. 672-673
Author(s):  
Ellen R. Wald ◽  
Barry Dashefsky
Keyword(s):  
High Risk ◽  
Lower Respiratory Tract ◽  
Respiratory Tract Disease ◽  
American Academy Of Pediatrics ◽  
Lower Respiratory Tract Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Tract Disease ◽  
New Guidelines ◽  
Do So

The new guidelines provided by the Committee on Infectious Diseases of the American Academy of Pediatrics on the Use of Ribavirin in the Treatment of Respiratory Syncytial Virus Infection (RSV) are perplexing and prompt concern: "Ribavirin treatment is recommended for the following patients hospitalized with RSV lower respiratory tract disease: a. infants at high risk for severe or complicated RSV infection, including those with complicated congenital heart disease (including pulmonary hypertension); those with bronchopulmonary dysplasia, . . ."1,pp502-503 The accompanying qualifier that "the recommendations in this statement do not indicate an exclusive course of treatment or procedure to be followed"1,p501 is important but insufficient to dampen the effect of the Committee's decision to change its former stance of merely urging consideration of the use of ribavirin for patients at high risk for complications2 to an unequivocal recommendation to do so.

Safety and Immunogenicity of the Ad26.RSV.preF Investigational Vaccine Coadministered With an Influenza Vaccine in Older Adults

2020 ◽  
Author(s):  
Jerald Sadoff ◽  
Els De Paepe ◽  
Wouter Haazen ◽  
Edmund Omoruyi ◽  
Arangassery R Bastian ◽  
...  
Keyword(s):  
Older Adults ◽  
Influenza Vaccine ◽  
Geometric Mean ◽  
Controlled Study ◽  
Tolerability Profile ◽  
Double Blind ◽  
Inhibition Antibody ◽  
Binding Antibody ◽  
Syncytial Virus ◽  
Significant Disease

Abstract Background Respiratory syncytial virus (RSV) and influenza cause significant disease burden in older adults. Overlapping RSV and influenza seasonality presents the opportunity to coadminister vaccines for both infections. This study assessed coadministration of the investigational vaccine, Ad26.RSV.preF, an adenovirus serotype 26 (Ad26) vector encoding RSV F protein stabilized in its prefusion conformation (pre-F), with a seasonal influenza vaccine in older adults. Methods In this phase 2a, double-blind, placebo-controlled study, 180 adults aged ≥60 years received Ad26.RSV.preF plus Fluarix on day 1 and placebo on day 29, or placebo plus Fluarix on day 1 and Ad26.RSV.preF on day 29 (control). Results The coadministration regimen had an acceptable tolerability profile. Reactogenicity was generally higher after Ad26.RSV.preF versus Fluarix, but symptoms were generally transient and mild or moderate. At 28 days after the first vaccination, the upper confidence intervals of the hemagglutination inhibition antibody geometric mean ratio (control/coadministration) for all influenza strains were <2, demonstrating noninferiority. Robust neutralizing and binding antibody responses to RSV A2 were observed in both groups. Conclusions Coadministration of Fluarix with Ad26.RSV.preF vaccine had an acceptable safety profile and showed no evidence of interference in immune response. The results are compatible with simultaneous seasonal vaccination with both vaccines. Clinical Trials Registration NCT03339713.

scholarly journals Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease

2014 ◽  
Vol 89 (3) ◽  
pp. 1564-1578 ◽  
Author(s):  
Yung-Chang Su ◽  
Dijana Townsend ◽  
Lara J. Herrero ◽  
Ali Zaid ◽  
Michael S. Rolph ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
The Elderly ◽  
Pulmonary Eosinophilia ◽  
Recurrent Wheezing ◽  
Interleukin 5 ◽  
Lower Respiratory Tract Disease ◽  
Syncytial Virus ◽  
Tract Disease ◽  
Deficient Mice

ABSTRACTHuman respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood.In vivostudies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin- and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin- and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load.IMPORTANCEThis study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity.

scholarly journals Follicular Bronchiolitis in a Nigerian Female Child: A Case Report and Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-5
Author(s):  
Nzechukwu Zimudo Ikeri ◽  
Godwin O. Umerah ◽  
Christopher Emeka Ugwu ◽  
Olugbenga Olusoji ◽  
Adekunle Adeyomoye ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Hospital Admissions ◽  
Female Child ◽  
Small Airways ◽  
Follicular Bronchiolitis ◽  
Lower Respiratory Tract Disease ◽  
Syncytial Virus ◽  
Tract Disease ◽  
Tract Infections

Small airways diseases are not uncommon in childhood. They account for about 28.4% of hospital admissions for lower respiratory tract infections in South West Nigeria, most of which are due to respiratory syncytial virus (RSV) infection. Noninfectious causes of small airways diseases, on the other hand, are poorly recognized and rarely feature in the differential diagnoses of chronic/recurrent lower respiratory tract disease in our environment. We present a case of follicular bronchiolitis in a 2.5-year-old Nigerian female who had left upper lobectomy on account of recurrent cough and progressive shortness of breath.

scholarly journals Phase 2b Study of an Ad26.RSV.preF Vaccine for Prevention of RSV-mediated Respiratory Tract Disease in Older Adults

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1050-1051
Author(s):  
Ann Falsey ◽  
Kristi Williams ◽  
Efi Gymnopoulou ◽  
Stephan Bart ◽  
John Ervin ◽  
...  
Keyword(s):  
Older Adults ◽  
Respiratory Tract ◽  
Neutralizing Antibodies ◽  
Lower Respiratory Tract ◽  
Specific Binding ◽  
Geometric Mean ◽  
Median Frequency ◽  
Respiratory Tract Disease ◽  
Double Blind ◽  
Tract Disease

Abstract Respiratory syncytial virus (RSV) may cause serious lower respiratory tract disease (LRTD) in older adults, and there is currently no licensed vaccine. CYPRESS (NCT03982199) is a randomized, double-blind, placebo-controlled Phase 2b proof-of-concept trial of an Ad26.RSV.preF-based vaccine for the prevention of RSV-mediated LRTD in older adults. Adults aged ≥65 years were randomized 1:1 before the RSV season to receive Ad26.RSV.preF-based vaccine or placebo. Acute respiratory infection symptoms were collected through a patient eDiary and/or clinician assessment until the end of the RSV season. The primary endpoint was the first occurrence of RTPCR-confirmed RSV-mediated LRTD according to any of 3 case definitions: (1) ≥3 symptoms of lower respiratory tract infection (LRTI), (2) ≥2 symptoms of LRTI, or (3) ≥2 symptoms of LRTI or ≥1 symptom of LRTI with ≥1 systemic symptom. Immunogenicity was assessed in a subset of approximately 200 participants. A total of 2891 participants in each study arm received study treatment. Vaccine efficacy was 80% (94.2% CI, 52.2-92.9%), 75% (50.1-88.5%), and 69.8% (43.7-84.7%) for case definition 1, 2, and 3, respectively (all P <0.001). In the vaccine arm, geometric mean fold increase in antibody titers 14 days after vaccination was 13.5 for RSV neutralizing antibodies and 8.6 for RSV prefusion F-specific binding antibodies, and median frequency of RSV-F-specific INFγ T-cells increased from 34 to 444 SFC/10^6 PBMC; no relevant changes were observed in the placebo arm. The Ad26.RSV.preF-based vaccine was highly effective against RSV-mediated LRTD through the first RSV season and elicited robust immune responses in older adults.

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