Minimum high dose ribavirin aerosol for the treatment of influenza in mice and respiratory syncytial virus in cotton rats

1991 ◽  
Vol 15 ◽  
pp. 142
Author(s):  
B.E. Gilbert ◽  
P.R. Wyde ◽  
M.W. Ambrose ◽  
H.L. Mover ◽  
S.Z. Wilson
Keyword(s):  
Respiratory Syncytial Virus ◽  
High Dose ◽  
Cotton Rats ◽  
Syncytial Virus

scholarly journals Single Immunization of a Vaccine Vectored by a Novel Recombinant Vaccinia Virus Affords Effective Protection Against Respiratory Syncytial Virus Infection in Cotton Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Marsha S. Russell ◽  
Sathya N. Thulasi Raman ◽  
Caroline Gravel ◽  
Wanyue Zhang ◽  
Annabelle Pfeifle ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Vaccinia Virus ◽  
High Efficiency ◽  
Vaccine Development ◽  
Nasal Administration ◽  
Effective Vaccine ◽  
High Dose ◽  
Cotton Rats ◽  
Syncytial Virus ◽  
Vectored Vaccine

Respiratory syncytial virus (RSV) is a leading cause of respiratory infections worldwide and disease management measures are hampered by the lack of a safe and effective vaccine against the infection. We constructed a novel recombinant RSV vaccine candidate based on a deletion mutant vaccinia virus platform, in that the host range genes E3L and K3L were deleted (designated as VACVΔE3LΔK3L) and a poxvirus K3L ortholog gene was used as a marker for the rapid and efficient selection of recombinant viruses. The safety of the modified vaccinia virus was investigated by intranasal administration of BALB/c mice with the modified vaccinia vector using a dose known to be lethal in the wild-type Western Reserve. Only a minor loss of body weight by less than 5% and mild pulmonary inflammation were observed, both of which were transient in nature following nasal administration of the high-dose modified vaccinia virus. In addition, the viruses were cleared from the lung in 2 days with no viral invasions of the brain and other vital organs. These results suggest that the virulence of the virus has been essentially abolished. We then investigated the efficiency of the vector for the delivery of vaccines against RSV through comparison with another RSV vaccine delivered by the widely used Modified Vaccinia virus Ankara (MVA) backbone. In the cotton rats, we found a single intramuscular administration of VACVΔE3LΔK3L-vectored vaccine elicited immune responses and protection at a level comparable to the MVA-vectored vaccine against RSV infection. The distinct features of this novel VACV vector, such as an E3L deletion for attenuation and a K3L ortholog for positive selection and high efficiency for vaccine delivery, could provide unique advantages to the application of VACV as a platform for vaccine development.

Systemic Immunoprophylaxis of Nasal Respiratory Syncytial Virus Infection in Cotton Rats

1995 ◽  
Vol 171 (2) ◽  
pp. 440-443 ◽  
Author(s):  
I. R. Sami ◽  
F. M. Piazza ◽  
S. A. Johnson ◽  
M. E. R. Darnell ◽  
M. G. Ottolini ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Infection ◽  
Respiratory Syncytial Virus Infection ◽  
Cotton Rats ◽  
Syncytial Virus

CL387626 exhibits marked and unusual antiviral activity against respiratory syncytial virus in tissue culture and in cotton rats

1998 ◽  
Vol 38 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Philip R Wyde ◽  
Donna K Moore-Poveda ◽  
Bryan O’Hara ◽  
Wei-Dong Ding ◽  
Boris Mitsner ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Respiratory Syncytial Virus ◽  
Antiviral Activity ◽  
Cotton Rats ◽  
Syncytial Virus

scholarly journals In Vitro and In Vivo Fitness of Respiratory Syncytial Virus Monoclonal Antibody Escape Mutants

2006 ◽  
Vol 80 (23) ◽  
pp. 11651-11657 ◽  
Author(s):  
Xiaodong Zhao ◽  
Enmei Liu ◽  
Fu-Ping Chen ◽  
Wayne M. Sullender
Keyword(s):  
Cell Culture ◽  
Monoclonal Antibody ◽  
Respiratory Syncytial Virus ◽  
Viral Population ◽  
Nucleotide Substitutions ◽  
Cotton Rats ◽  
Syncytial Virus ◽  
In Vivo Growth

ABSTRACT Respiratory syncytial virus (RSV) is the only infectious disease for which a monoclonal antibody (MAb) is used in humans. Palivizumab (PZ) is a humanized murine MAb to the F protein of RSV. PZ-resistant viruses appear after in vitro and in vivo growth of RSV in the presence of PZ. Fitness for replication could be a determinant of the likelihood of dissemination of resistant viruses. We assessed the fitness of two PZ-resistant viruses (F212 and MP4). F212 grew less well in cell culture than the parent A2 virus and was predicted to be less fit than A2. Equal amounts of F212 and A2 were mixed and passaged in cell culture. F212 disappeared from the viral population, indicating it was less fit than the A2 virus. The MP4 virus grew as well as A2 in culture and in cotton rats. A2/MP4 virus input ratios of 1:1, 10:1, 100:1, and 1,000:1 were compared in competitive replication. For all input ratios except 1,000:1, the MP4 virus became dominant, supplanting the A2 virus. The MP4 virus also dominated the A2 virus during growth in cotton rats. Thus, the mutant MP4 virus was more fit than A2 virus in both in vitro and in vivo competitive replication. Whether this fitness difference was due to the identified nucleotide substitutions in the F gene or to mutations elsewhere in the genome is unknown. Understanding the mechanisms by which mutant virus fitness increased or decreased could prove useful for consideration in attenuated vaccine design efforts.

scholarly journals Recombinant subtype A and B human respiratory syncytial virus clinical isolates co-infect the respiratory tract of cotton rats

2020 ◽  
Vol 101 (10) ◽  
pp. 1056-1068
Author(s):  
Linda J. Rennick ◽  
Sham Nambulli ◽  
Ken Lemon ◽  
Grace Y. Olinger ◽  
Nicholas A. Crossland ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Reverse Genetics ◽  
Fluorescent Protein ◽  
Human Respiratory Syncytial Virus ◽  
Subtype B ◽  
Cotton Rats ◽  
Syncytial Virus ◽  
Subtype A

Human respiratory syncytial virus (HRSV) is an important respiratory pathogen causing a spectrum of illness, from common cold-like symptoms, to bronchiolitis and pneumonia requiring hospitalization in infants, the immunocompromised and the elderly. HRSV exists as two antigenic subtypes, A and B, which typically cycle biannually in separate seasons. There are many unresolved questions in HRSV biology regarding the interactions and interplay of the two subtypes. Therefore, we generated a reverse genetics system for a subtype A HRSV from the 2011 season (A11) to complement our existing subtype B reverse genetics system. We obtained the sequence (HRSVA11) directly from an unpassaged clinical sample and generated the recombinant (r) HRSVA11. A version of the virus expressing enhanced green fluorescent protein (EGFP) from an additional transcription unit in the fifth (5) position of the genome, rHRSVA11EGFP(5), was also generated. rHRSVA11 and rHRSVA11EGFP(5) grew comparably in cell culture. To facilitate animal co-infection studies, we derivatized our subtype B clinical isolate using reverse genetics toexpress the red fluorescent protein (dTom)-expressing rHRSVB05dTom(5). These viruses were then used to study simultaneous in vivo co-infection of the respiratory tract. Following intranasal infection, both rHRSVA11EGFP(5) and rHRSVB05dTom(5) infected cotton rats targeting the same cell populations and demonstrating that co-infection occurs in vivo. The implications of this finding on viral evolution are important since it shows that inter-subtype cooperativity and/or competition is feasible in vivo during the natural course of the infection.

scholarly journals Evolution of protection after maternal immunization for respiratory syncytial virus in cotton rats

2021 ◽  
Author(s):  
Jorge C.G. Blanco ◽  
Lori McGinnes-Cullen ◽  
Arash Kamali ◽  
Fatoumata Sylla ◽  
Marina Boukhavalova ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Neutralizing Antibody ◽  
Wild Type ◽  
Cotton Rat ◽  
Before And After ◽  
Boost Immunization ◽  
Cotton Rats ◽  
Antibody Titers ◽  
Syncytial Virus ◽  
Efficient Transfer

Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life.  In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge (Blanco, et al Journal of Virology 93: e00914-19, https://doi.org/10.1128/JVI.00914-19).  Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization.  We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth.   However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age.  This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy.  The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.

scholarly journals Simultaneous Administration of Recombinant Measles Viruses Expressing Respiratory Syncytial Virus Fusion (F) and Nucleo (N) Proteins Induced Humoral and Cellular Immune Responses in Cotton Rats

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 27 ◽  
Author(s):  
Yoshiaki Yamaji ◽  
Akihito Sawada ◽  
Yosuke Yasui ◽  
Takashi Ito ◽  
Tetsuo Nakayama
Keyword(s):  
Respiratory Syncytial Virus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Simultaneous Administration ◽  
Cellular Immune Responses ◽  
Immunization Group ◽  
Cotton Rats ◽  
Ifn Γ ◽  
Syncytial Virus ◽  
Cellular Immune

We previously reported that recombinant measles virus expressing the respiratory syncytial virus (RSV) fusion protein (F), MVAIK/RSV/F, induced neutralizing antibodies against RSV, and those expressing RSV-NP (MVAIK/RSV/NP) and M2-1 (MVAIK/RSV/M2-1) induced RSV-specific CD8+/IFN-γ+ cells, but not neutralizing antibodies. In the present study, MVAIK/RSV/F and MVAIK/RSV/NP were simultaneously administered to cotton rats and immune responses and protective effects were compared with MVAIK/RSV/F alone. Sufficient neutralizing antibodies against RSV and RSV-specific CD8+/IFN-γ+ cells were observed after re-immunization with simultaneous administration. After the RSV challenge, CD8+/IFN-γ+ increased in spleen cells obtained from the simultaneous immunization group in response to F and NP peptides. Higher numbers of CD8+/IFN-γ+ and CD4+/IFN-γ+ cells were detected in lung tissues from the simultaneous immunization group after the RSV challenge. No detectable RSV was recovered from lung homogenates in the immunized groups. Mild inflammatory reactions with the thickening of broncho-epithelial cells and the infiltration of inflammatory cells were observed in lung tissues obtained from cotton rats immunized with MVAIK/RSV/F alone after the RSV challenge. No inflammatory responses were observed after the RSV challenge in the simultaneous immunization groups. The present results indicate that combined administration with MVAIK/RSV/F and MVAIK/RSV/NP induces humoral and cellular immune responses and shows effective protection against RSV, suggesting the importance of cellular immunity.

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