scholarly journals Mucosal Immunization with Live Recombinant Bovine Respiratory Syncytial Virus (BRSV) and Recombinant BRSV Lacking the Envelope Glycoprotein G Protects against Challenge with Wild-Type BRSV

2002 ◽  
Vol 76 (23) ◽  
pp. 12355-12359 ◽  
Author(s):  
Ulrike Schmidt ◽  
Jörg Beyer ◽  
Ulf Polster ◽  
Laurel J. Gershwin ◽  
Ursula J. Buchholz

ABSTRACT Recombinant bovine respiratory syncytial virus (rBRSV) and an rBRSV deletion mutant lacking the G gene (rBRSVΔG) were characterized in calves with respect to replication competence, attenuation, and protective efficacy as live-attenuated BRSV vaccines. Both recombinant viruses were safe and induced protection against a BRSV challenge infection. rBRSV replicated efficiently in the upper respiratory tract. Intranasal immunization with rBRSVΔG led to infection but not to mucosal virus replication. Neutralizing antibodies were induced by rBRSV and rBRSVΔG. Thus, the BRSV attachment glycoprotein G seems to be dispensable in vaccinating calves against BRSV.

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Birgit Makoschey ◽  
Anna Catharina Berge

AbstractBovine Respiratory Syncytial virus (BRSV) and Bovine Parainfluenza 3 virus (BPIV3) are closely related viruses involved in and both important pathogens within bovine respiratory disease (BRD), a major cause of morbidity with economic losses in cattle populations around the world. The two viruses share characteristics such as morphology and replication strategy with each other and with their counterparts in humans, HRSV and HPIV3. Therefore, BRSV and BPIV3 infections in cattle are considered useful animal models for HRSV and HPIV3 infections in humans.The interaction between the viruses and the different branches of the host’s immune system is rather complex. Neutralizing antibodies seem to be a correlate of protection against severe disease, and cell-mediated immunity is thought to be essential for virus clearance following acute infection. On the other hand, the host’s immune response considerably contributes to the tissue damage in the upper respiratory tract.BRSV and BPIV3 also have similar pathobiological and epidemiological features. Therefore, combination vaccines against both viruses are very common and a variety of traditional live attenuated and inactivated BRSV and BPIV3 vaccines are commercially available.


Author(s):  
Dr Mark Harrison

15.1 Rhinovirus, 209 15.2 Influenza, 210 15.3 Parainfluenza, 211 15.4 Respiratory syncytial virus (RSV), 211 • There are more than 100 different serotypes of rhinovirus. • Rhinovirus is chiefly limited to upper respiratory tract infections and is the major cause of the common cold....


2018 ◽  
Vol 2018 ◽  
pp. 1-3 ◽  
Author(s):  
Ryan Leibrandt ◽  
Kenneth Angelino ◽  
Monique Vizel-Schwartz ◽  
Ilan Shapira

Paroxysmal cold hemoglobinuria (PCH) is a rare form of cold autoimmune hemolytic anemia first discovered in the early 20th century in adults with tertiary syphilis. Today, it is more commonly seen in children as a life-threatening anemia during a viral upper respiratory tract infection (URI). Although respiratory syncytial virus (RSV) has previously been reported to cause PCH in a child, herein we present the first documented case in an adult. The Donath–Landsteiner (DL) test, the diagnostic test for PCH, was positive on two separate occasions. The patient was treated successfully with warming and avoidance of cold temperatures. To facilitate identification of this rare entity by clinicians, we include a discussion about the pathophysiology, diagnosis, and treatment of PCH.


2000 ◽  
Vol 74 (8) ◽  
pp. 3455-3463 ◽  
Author(s):  
Hélène Plotnicky-Gilquin ◽  
Alain Robert ◽  
Laurent Chevalet ◽  
Jean-Francois Haeuw ◽  
Alain Beck ◽  
...  

ABSTRACT We analyzed the protective mechanisms induced against respiratory syncytial virus subgroup A (RSV-A) infection in the lower and upper respiratory tracts (LRT and URT) of BALB/c mice after intraperitoneal immunization with a recombinant fusion protein incorporating residues 130 to 230 of RSV-A G protein (BBG2Na). Mother-to-offspring antibody (Ab) transfer and adoptive transfer of BBG2Na-primed B cells into SCID mice demonstrated that Abs are important for LRT protection but have no effect on URT infection. In contrast, RSV-A clearance in the URT was achieved in a dose-dependent fashion after adoptive transfer of BBG2Na-primed T cells, while it was abolished in BBG2Na-immunized mice upon in vivo depletion of CD4+, but not CD8+, T cells. Furthermore, the conserved RSV-A G protein cysteines and residues 193 and 194, overlapping the recently identified T helper cell epitope on the G protein (P. W. Tebbey et al., J. Exp. Med. 188:1967–1972, 1998), were found to be essential for URT but not LRT protection. Taken together, these results demonstrate for the first time that CD4+ T cells induced upon parenteral immunization with an RSV G protein fragment play a critical role in URT protection of normal mice against RSV infection.


2000 ◽  
Vol 74 (19) ◽  
pp. 9317-9321 ◽  
Author(s):  
Michael N. Teng ◽  
Stephen S. Whitehead ◽  
Alison Bermingham ◽  
Marisa St. Claire ◽  
William R. Elkins ◽  
...  

ABSTRACT Mutant recombinant respiratory syncytial viruses (RSV) which cannot express the NS1 and M2-2 proteins, designated rA2ΔNS1 and rA2ΔM2-2, respectively, were evaluated as live-attenuated RSV vaccines. The rA2ΔNS1 virus contains a large deletion that should have the advantageous property of genetic stability during replication in vitro and in vivo. In vitro, rA2ΔNS1 replicated approximately 10-fold less well than wild-type recombinant RSV (rA2), while rA2ΔM2-2 had delayed growth kinetics but reached a final titer similar to that of rA2. Each virus was administered to the respiratory tracts of RSV-seronegative chimpanzees to assess replication, immunogenicity, and protective efficacy. The rA2ΔNS1 and rA2ΔM2-2 viruses were 2,200- to 55,000-fold restricted in replication in the upper and lower respiratory tracts but induced a level of RSV-neutralizing antibody in serum that was only slightly reduced compared to the level induced by wild-type RSV. The replication of wild-type RSV in immunized chimpanzees after challenge was reduced more than 10,000-fold at each site. Importantly, rA2ΔNS1 and rA2ΔM2-2 were 10-fold more restricted in replication in the upper respiratory tract than was thecpts248/404 virus, a vaccine candidate that retained mild reactogenicity in the upper respiratory tracts of 1-month-old infants. Thus, either rA2ΔNS1 or rA2ΔM2-2 might be appropriately attenuated for this age group, which is the major target population for an RSV vaccine. In addition, these results show that neither NS1 nor M2-2 is essential for RSV replication in vivo, although each is important for efficient replication.


2015 ◽  
Vol 89 (16) ◽  
pp. 8258-8266 ◽  
Author(s):  
Anne L. Hotard ◽  
Elizabeth Laikhter ◽  
Kelsie Brooks ◽  
Tina V. Hartert ◽  
Martin L. Moore

ABSTRACTThere are two subgroups of respiratory syncytial virus (RSV), A and B, and within each subgroup, isolates are further divided into clades. Several years ago, multiple subgroup B isolates which contained a duplication of 60 nucleotides in the glycoprotein (G) gene were described. These isolates were given a new clade designation of BA based on the site of isolation, Buenos Aires, Argentina. BA RSV strains have since become the predominant circulating clade of RSV B viruses. We hypothesized that the duplicated region in G serves to enhance the function of G in the virus life cycle. We generated recombinant viruses that express a consensus BA G gene or a consensus BA G gene lacking the duplication (GΔdup). We determined that the duplicated region functions during virus attachment to cells. Additionally, we showed thatin vitro, the virus containing the duplication has a fitness advantage compared to the virus without the duplication. Our data demonstrate that the duplicated region in the BA strain G protein augments virus attachment and fitness.IMPORTANCERespiratory syncytial virus (RSV) is an important pathogen for infants for which there is no vaccine. Different strains of RSV circulate from year to year, and the predominating strains change over time. Subgroup B RSV strains with a duplication in the attachment glycoprotein (G) emerged and then became the dominant B genotype. We found that a recombinant virus harboring the duplication bound more efficiently to cells and was more fit than a recombinant strain lacking the duplication. Our work advances a mechanism for an important natural RSV mutation.


2015 ◽  
Vol 89 (16) ◽  
pp. 8193-8205 ◽  
Author(s):  
Sandra Fuentes ◽  
Elizabeth M. Coyle ◽  
Hana Golding ◽  
Surender Khurana

ABSTRACTNew efforts are under way to develop a vaccine against respiratory syncytial virus (RSV) that will provide protective immunity without the potential for vaccine-associated disease enhancement such as that observed in infants following vaccination with formalin-inactivated RSV vaccine. In addition to the F fusion protein, the G attachment surface protein is a target for neutralizing antibodies and thus represents an important vaccine candidate. However, glycosylated G protein expressed in mammalian cells has been shown to induce pulmonary eosinophilia upon RSV infection in a mouse model. In the current study, we evaluated in parallel the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain (amino acids 67 to 298) expressed inEscherichia coli(REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model. Vaccination with REG generated neutralizing antibodies against RSV A2 in 7/11 BALB/c mice, while RMG did not elicit neutralizing antibodies. Total serum binding antibodies against the recombinant proteins (both REG and RMG) were measured by surface plasmon resonance (SPR) and were found to be >10-fold higher for REG- than for RMG-vaccinated animals. Reduction of lung viral loads to undetectable levels after homologous (RSV-A2) and heterologous (RSV-B1) viral challenge was observed in 7/8 animals vaccinated with REG but not in RMG-vaccinated animals. Furthermore, enhanced lung pathology and elevated Th2 cytokines/chemokines were observed exclusively in animals vaccinated with RMG (but not in those vaccinated with REG or phosphate-buffered saline [PBS]) after homologous or heterologous RSV challenge. This study suggests that bacterially produced unglycosylated G protein could be developed alone or as a component of a protective vaccine against RSV disease.IMPORTANCENew efforts are under way to develop vaccines against RSV that will provide protective immunity without the potential for disease enhancement. The G attachment protein represents an important candidate for inclusion in an effective RSV vaccine. In the current study, we evaluated the safety and protective efficacy of the RSV A2 recombinant unglycosylated G protein ectodomain produced inE. coli(REG) and those of glycosylated G produced in mammalian cells (RMG) in a mouse RSV challenge model (strains A2 and B1). The unglycosylated G generated high protective immunity and no lung pathology, even in animals that lacked anti-RSV neutralizing antibodies prior to RSV challenge. Control of viral loads correlated with antibody binding to the G protein. In contrast, the glycosylated G protein provided poor protection and enhanced lung pathology after RSV challenge. Therefore, bacterially produced unglycosylated G protein holds promise as an economical approach to a protective vaccine against RSV.


2010 ◽  
Vol 8 (2) ◽  
pp. 197-199 ◽  
Author(s):  
Amilton Mouro ◽  
Luci Black Tabacow Hidal ◽  
Marines Dalla Valle Martino ◽  
Jacyr Pasternark

ABSTRACT Objective: To evaluate the prevalence of pathogens in the upper respiratory tract according to age at a tertiary care hospital in the city of São Paulo. Methods: A total of 6,144 biological material tests from upper respiratory airways were analyzed: 740 bacterial cultures, 726 virus screenings and 4,678 rapid tests for S. pyogenes. Results: The most frequently found etiological agent was respiratory syncytial virus (29.6%; 215/726). The main agents detected per age groups were: respiratory syncytial virus (25.34%; 184/726) in patients aged 28 days-3 years; S. pyogenes (9.5%; 70/740) in 3-12 year-old children; influenza virus (8.8%; 64/726) in adults (18-59 years). Conclusions: The etiologic agents of upper respiratory infections vary according to age and imply diverse clinical and therapeutic management.


Intervirology ◽  
2008 ◽  
Vol 51 (2) ◽  
pp. 112-115 ◽  
Author(s):  
Jesus F. Bermejo-Martin ◽  
Alberto Tenorio ◽  
Raul Ortiz de Lejarazu ◽  
Jose M. Eiros ◽  
Vanesa Matías ◽  
...  

1990 ◽  
Vol 105 (3) ◽  
pp. 609-618 ◽  
Author(s):  
K. G. Nicholson ◽  
D. J. Baker ◽  
A. Farquhar ◽  
D. Hurd ◽  
J. Kent ◽  
...  

SUMMARYOccupants of 482 long-stay and 33 short-stay beds in 11 Leicester City Council homes for the elderly were studied during a 30-week period from September 1988 to March 1989 to determine the incidence, aetiology, morbidity, and mortality of acute upper respiratory tract viral infections and the use of influenza vaccine.Influenza immunization rates by home ranged from 15·4 to 90% (mean 45%). There were no differences in the distribution of medical conditions by home. The highest immunization rates were seen in people with chest disease (77%), heart disease (60%), diabetes (56%), and those with three medical conditions (75%). There was an average of 0·7 upper respiratory episodes per bed per annum with a mortality of 3·4% (6/179). Half of all episodes were seen by a general medical practitioner and 81 of 90 (90%) referrals were prescribed antibiotics costing approximately £7.50 per patient. Lower respiratory tract complications developed during 45 (25%) of 179 episodes including 3 of 12 coronavirus infections, 3 of 9 respiratory syncytial virus infections, 2 of 4 adenovirus infections, 1 of 11 rhinovirus infections, but none of 5 influenza infections. Respiratory infections were caused mostly by pathogens other than influenza virus during the influenza period documented nationally. This highlights the role of coronaviruses, respiratory syncytial virus, and unidentified agents in the elderly, and questions the assumptions made in American estimates on the impact of influenza and the value of influenza vaccines.


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