scholarly journals Vaccine containing G protein fragment and recombinant baculovirus expressing M2 protein induces protective immunity to respiratory syncytial virus

2019 ◽  
Vol 8 (1) ◽  
pp. 43
Author(s):  
Yeong-Min Jo ◽  
Jungwoo Kim ◽  
Jun Chang
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Protective Immunity ◽  
Recombinant Baculovirus ◽  
M2 Protein ◽  
Protein Fragment ◽  
Syncytial Virus

scholarly journals CD4+ T-Cell-Mediated Antiviral Protection of the Upper Respiratory Tract in BALB/c Mice following Parenteral Immunization with a Recombinant Respiratory Syncytial Virus G Protein Fragment

2000 ◽  
Vol 74 (8) ◽  
pp. 3455-3463 ◽  
Author(s):  
Hélène Plotnicky-Gilquin ◽  
Alain Robert ◽  
Laurent Chevalet ◽  
Jean-Francois Haeuw ◽  
Alain Beck ◽  
...  
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Adoptive Transfer ◽  
Critical Role ◽  
Upper Respiratory Tract ◽  
Protein Fragment ◽  
Parenteral Immunization ◽  
Upper Respiratory ◽  
Syncytial Virus

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.

scholarly journals Nonglycosylated G-Protein Vaccine Protects against Homologous and Heterologous Respiratory Syncytial Virus (RSV) Challenge, while Glycosylated G Enhances RSV Lung Pathology and Cytokine Levels

2015 ◽  
Vol 89 (16) ◽  
pp. 8193-8205 ◽  
Author(s):  
Sandra Fuentes ◽  
Elizabeth M. Coyle ◽  
Hana Golding ◽  
Surender Khurana
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Mammalian Cells ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Lung Pathology ◽  
Content Type ◽  
Viral Loads ◽  
Syncytial Virus

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.

scholarly journals Absence of Lung Immunopathology Following Respiratory Syncytial Virus (RSV) Challenge in Mice Immunized with a Recombinant RSV G Protein Fragment

Virology ◽  
1999 ◽  
Vol 258 (1) ◽  
pp. 128-140 ◽  
Author(s):  
Hélène Plotnicky-Gilquin ◽  
Thierry Huss ◽  
Jean-Pierre Aubry ◽  
Jean-François Haeuw ◽  
Alain Beck ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Protein Fragment ◽  
Syncytial Virus

scholarly journals Eliminating a Region of Respiratory Syncytial Virus Attachment Protein Allows Induction of Protective Immunity without Vaccine-enhanced Lung Eosinophilia

1998 ◽  
Vol 187 (11) ◽  
pp. 1921-1926 ◽  
Author(s):  
Tim E. Sparer ◽  
Stephen Matthews ◽  
Tracy Hussell ◽  
Aaron J. Rae ◽  
Blanca Garcia-Barreno ◽  
...  
Keyword(s):  
Amino Acids ◽  
Weight Loss ◽  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Protective Immunity ◽  
Virus Disease ◽  
Recombinant Vaccinia Virus ◽  
Wild Type ◽  
Lung Eosinophilia ◽  
Syncytial Virus

In a murine model of respiratory syncytial virus disease, prior sensitization to the attachment glycoprotein (G) leads to pulmonary eosinophilia and enhanced illness. Three different approaches were taken to dissect the region of G responsible for enhanced disease and protection against challenge. First, mutant viruses, containing frameshifts that altered the COOH terminus of the G protein, were used to challenge mice sensitized by scarification with recombinant vaccinia virus (rVV) expressing wild-type G. Second, cDNA expressing these mutated G proteins were expressed by rVV and used to vaccinate mice before challenge with wild-type respiratory syncytial virus (RSV). These studies identified residues 193–205 to be responsible for G-induced weight loss and lung eosinophilia and showed that this region was not was not necessary for induction of protective immunity. Third, mice were sensitized using an rVV that expressed only amino acids 124–203 of the G protein. Upon RSV challenge, mice sensitized with this rVV developed enhanced weight loss and eosinophilia. This is the first time that a region within RSV (amino acids 193–203) has been shown to be responsible for induction of lung eosinophilia and disease enhancement. Moreover, we now show that it is possible to induce protective immunity with an altered G protein without inducing a pathological response.

scholarly journals Effect of Previous Respiratory Syncytial Virus Infection on Murine Immune Responses to F and G Protein-Containing Virus-Like Particles

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Lori McGinnes Cullen ◽  
Madelyn R. Schmidt ◽  
Trudy G. Morrison
Keyword(s):  
Respiratory Syncytial Virus ◽  
G Protein ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Immune Memory ◽  
Effective Vaccine ◽  
F Protein ◽  
Virus Like Particles ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACTMost individuals are infected with respiratory syncytial virus (RSV) by age two, but infection does not result in long-term protective immunity to subsequent infections. Previous RSV infection may, however, impact responses to an RSV vaccine. The goal of these studies was to explore the effect of previous RSV infection on murine antibody responses to RSV F and G protein-containing virus-like particles (VLP), comparing responses to those resulting from VLP immunization of RSV-naive animals. These studies showed that after RSV infection, immunization with a single dose of VLPs containing a conformation-stabilized prefusion F protein stimulated high titers of neutralizing antibodies (NA), while an immunization with post-F-containing VLPs or a second RSV infection only weakly stimulated NA, even though total anti-F protein IgG antibody levels in both VLP-immunized animals were similar. Furthermore, single pre-F or post-F VLP immunization of animals previously infected (primed) with RSV resulted in total anti-F antibody titers that were 10- to 12-fold higher than titers after a VLP prime and boost of RSV-naive animals or after two consecutive RSV infections. The avidities of serum antibodies as well as numbers of splenic B cells and bone marrow cells after different immunization protocols were also assessed. The combined results show that RSV infection can quite effectively prime animals for the production of protective antibodies that can be efficiently activated by a pre-F VLP boost but not by a post-F VLP boost or a second RSV infection.IMPORTANCEHumans may experience repeated infections caused by the same serotype of respiratory syncytial virus (RSV), in contrast to infections with most other viruses, indicating that immune memory responses to RSV are defective. However, the effects of any residual but nonprotective immunity on responses to RSV vaccines are not clear. This study demonstrates that a VLP vaccine candidate containing a stabilized prefusion F protein can robustly stimulate protective immunity in animals previously infected with RSV, while a second RSV infection or a postfusion F-containing VLP cannot. This result shows that a properly constructed immunogen can be an effective vaccine in animals previously infected with RSV. The results also suggest that the defect in RSV memory is not in the induction of that memory but rather in its activation by a subsequent RSV infection.

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