scholarly journals Genomics of Human Respiratory Syncytial Virus Vaccine Attenuation

2019 ◽  
Author(s):  
Thomas Junier ◽  
Laurent Kaiser ◽  
Nimisha Chaturvedi ◽  
Tina Hartert ◽  
Jacques Fellay
Keyword(s):  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Lower Respiratory Tract ◽  
Sequence Data ◽  
Wild Type ◽  
Live Attenuated Vaccine ◽  
Vaccine Candidates ◽  
Syncytial Virus ◽  
Respiratory Syncytial Virus Vaccine

ABSTRACTThe human orthopneumovirus (HRSV) is a major cause of lower respiratory tract infection in children worldwide. Despite decades of efforts, no vaccine is available. In this work, we report mutations that are frequent in vaccine candidates and rare in wild-type genomes, taking into account all the publicly available HRSV sequence data. These mutations are different from the ones already known to attenuate the virus, and thus may contribute to the effort towards producing a live attenuated vaccine against HRSV.

scholarly journals Recombinant Respiratory Syncytial Virus Bearing a Deletion of either the NS2 or SH Gene Is Attenuated in Chimpanzees

1999 ◽  
Vol 73 (4) ◽  
pp. 3438-3442 ◽  
Author(s):  
Stephen S. Whitehead ◽  
Alexander Bukreyev ◽  
Michael N. Teng ◽  
Cai-Yen Firestone ◽  
Marisa St. Claire ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Recombinant Virus ◽  
Lower Respiratory Tract ◽  
Vaccine Candidate ◽  
Upper Respiratory Tract ◽  
Wild Type ◽  
Vaccine Candidates ◽  
Upper Respiratory ◽  
Syncytial Virus

ABSTRACT The NS2 and SH genes of respiratory syncytial virus (RSV) have been separately deleted from a recombinant wild-type RSV strain, A2 (M. N. Teng and P. L. Collins, J. Virol. 73:466–473, 1998; A. Bukreyev et al., J. Virol. 71:8973–8982, 1997; and this study). The resulting viruses, designated rA2ΔNS2 and rA2ΔSH, were administered to chimpanzees to evaluate their levels of attenuation and immunogenicity. Recombinant virus rA2ΔNS2 replicated to moderate levels in the upper respiratory tract, was highly attenuated in the lower respiratory tract, and induced significant resistance to challenge with wild-type RSV. The replication of rA2ΔSH virus was only moderately reduced in the lower, but not the upper, respiratory tract. However, chimpanzees infected with either virus developed significantly less rhinorrhea than those infected with wild-type RSV. These findings demonstrate that a recombinant RSV mutant lacking either the NS2 or SH gene is attenuated and indicate that these deletions may be useful as attenuating mutations in new, live recombinant RSV vaccine candidates for both pediatric and elderly populations. The ΔSH mutation was incorporated into a recombinant form of thecpts248/404 vaccine candidate, was evaluated for safety in seronegative chimpanzees, and can now be evaluated as a vaccine for humans.

scholarly journals The Use of Aerosolized Ribavirin in Respiratory Syncytial Virus Lower Respiratory Tract Infections in Adult Immunocompromised Patients: A Systematic Review

2019 ◽  
Vol 55 (4) ◽  
pp. 224-235
Author(s):  
Lisa Avery ◽  
Charles Hoffmann ◽  
Karen M. Whalen
Keyword(s):  
Systematic Review ◽  
Mechanical Ventilation ◽  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Respiratory Tract ◽  
Respiratory Tract Infection ◽  
Lower Respiratory Tract ◽  
Adverse Reactions ◽  
Immunocompromised Patients ◽  
Syncytial Virus

Introduction: Respiratory syncytial virus (RSV)–associated lower respiratory tract infection (LRTI) is a concern in immunocompromised patients. Aerosolized ribavirin (RBV AER) is used for treatment of RSV LRTI; however, adverse events and rising drug costs remain a challenge for patient management. The purpose of this systematic review is to summarize the efficacy and adverse event profile of RBV AER for the treatment of hospitalized RSV LRTI in immunocompromised adult patients. Methods: A Medline/PubMed, Embase, Google Scholar, Clinicaltrials.gov, and Cochrane Library database search was conducted from 1966 to January 2019 for the use of RBV AER. Search strategy: [(ribavirin OR ICN1229) AND (“administration, oral” OR “oral” OR “administration, inhalation” OR “inhalation)] AND (“respiratory tract infection” OR “pneumonia”). Studies were reviewed if adult patients were hospitalized, immunocompromised, had RSV LRTI, received RBV AER, and included the outcome of mortality and/or adverse reactions. Methodological quality was assessed using the Cochrane Collaboration GRADE approach. Results: A total of 1787 records were identified and 15 articles met inclusion criteria: hematopoietic stem cell transplant (HSCT)/bone marrow transplant (n = 8), other malignancy/neutropenic (n = 2), solid organ transplant (n = 5). All of the trials are observational with a low quality rating; therefore, a meta-analysis was not performed. The 30-day mortality in studies that contain >10 patients with HSCT, malignancy, and transplant range from 0 to 15.4%, 6.3%, and 0 to 27%, respectively. Improved mortality was cited in 4 studies when RBV AER started before mechanical ventilation or within 2 weeks of symptom onset. Only 3 studies had comparative mortality data with RBV AER and RBV PO. Adverse reactions were reported in 5 studies and included psychiatric manifestations (anxiety, depression, feeling of isolation; n = 14), wheezing/bronchospasm (n = 6), snowflakes/hail blowing in face (n = 6), and precipitation in ventilator tubing (n = 5). Conclusion: There is a lack of high quality, comparative trials on the use of RBV AER for the treatment of RSV LRTI in adult hospitalized immunocompromised patients. There may be a mortality benefit when RBV AER is initiated early after diagnosis or prior to mechanical ventilation, but requires further study. Patient isolation and psychological effects must be weighed against the benefit of therapy.

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