Influenza virus vaccine expressing fusion and attachment protein epitopes of respiratory syncytial virus induces protective antibodies in BALB/c mice

Bian, Chengrong; Liu, Shuzhen; Liu, Na; Zhang, Guangzhou; Li, Xing; Song, Yingwei; Duan, Yueqiang; Gu, Huiying; Zhou, Yue; Zhang, Peirui; Li, Zhiwei; Zhang, Keming; Wang, Zhaohai; Zhang, Shaogeng; Wang, Xiliang; Yang, Peng

doi:10.1016/j.antiviral.2014.01.022

Cited by 19 publications

(11 citation statements)

References 26 publications

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“…Therefore, a restricted domain of the RSV G protein in a platform that presents this G fragment in a safe live vector may influence the pattern of host immune responses, which may confer protection against RSV without pulmonary RSV disease. In support of this concept, protection against RSV was provided by two immunizations with recombinant influenza virus harboring multiple RSV F and G-derived epitopes that were introduced into the nonstructural (NS1) protein (Bian et al, 2014). Probably due to the nature of intracellular expression of RSV G and F epitopes together with NS1 genes, protective efficacy of single G or F epitope-containing recombinant influenza virus was reported to be low (Bian et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In support of this concept, protection against RSV was provided by two immunizations with recombinant influenza virus harboring multiple RSV F and G-derived epitopes that were introduced into the nonstructural (NS1) protein (Bian et al, 2014). Probably due to the nature of intracellular expression of RSV G and F epitopes together with NS1 genes, protective efficacy of single G or F epitope-containing recombinant influenza virus was reported to be low (Bian et al, 2014). Results in our study showed that G domains in recombinant PR8/RSV.HA-G viruses were incorporated into virions at a comparable or higher level as in RSV and a single dose may be sufficient to confer protection.…”

Section: Discussionmentioning

confidence: 99%

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Recombinant influenza virus carrying the conserved domain of respiratory syncytial virus (RSV) G protein confers protection against RSV without inflammatory disease

et al. 2015

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Respiratory syncytial virus (RSV) is one of the most important causes for viral lower respiratory tract disease in humans. There is no licensed RSV vaccine. Here, we generated recombinant influenza viruses (PR8/RSV.HA-G) carrying the chimeric constructs of hemagglutinin (HA) and central conserved-domains of the RSV G protein. PR8/RSV.HA-G virus showed lower pathogenicity without compromising immunogenicity in mice. Single intranasal inoculation of mice with PR8/RSV.HA-G induced IgG2a isotype dominant antibodies and RSV neutralizing activity. Mice with single intranasal inoculation of PR8/RSV.HA-G were protected against RSV infection as evidenced by significant reduction of lung viral loads to a detection limit upon RSV challenge. PR8/RSV.HA-G inoculation of mice did not induce pulmonary eosinophilia and inflammation upon RSV infection. These findings support a concept that recombinant influenza viruses carrying the RSV G conserved-domain can be developed as a promising RSV vaccine candidate without pulmonary disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Recombinant influenza virus carrying the conserved domain of respiratory syncytial virus (RSV) G protein confers protection against RSV without inflammatory disease

et al. 2015

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“…It is speculated that a restricted domain containing RSV neutralizing epitopes in a safe live vector may confer protective immune responses without inflammatory viral disease. In support of this concept, protection against RSV was reported by two immunizations with recombinant influenza virus harboring multiple RSV F and G-derived epitopes that were introduced into the nonstructural (NS1) protein (Bian et al, 2014). Probably due to the nature of intracellular expression of RSV G and F epitopes under the NS1 genes, protection by single G or F epitope-containing recombinant influenza virus was low or not effective even after prime-boost immunizations (Bian et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In support of this concept, protection against RSV was reported by two immunizations with recombinant influenza virus harboring multiple RSV F and G-derived epitopes that were introduced into the nonstructural (NS1) protein (Bian et al, 2014). Probably due to the nature of intracellular expression of RSV G and F epitopes under the NS1 genes, protection by single G or F epitope-containing recombinant influenza virus was low or not effective even after prime-boost immunizations (Bian et al, 2014). In our study, a single immunization of chimeric PR8/RSV.HA-F virus may be sufficient to induce protective immunity to RSV, probably because of expression in a chimeric HA-F protein.…”

Section: Discussionmentioning

confidence: 99%

Recombinant influenza virus expressing a fusion protein neutralizing epitope of respiratory syncytial virus (RSV) confers protection without vaccine-enhanced RSV disease

et al. 2015

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Respiratory syncytial virus (RSV) is the leading cause of viral bronchiolitis in both children and the elderly. There is no vaccine available for the prevention of RSV infection. Here, we generated recombinant influenza virus (PR8/RSV.HA-F) expressing an RSV F243–294 neutralizing epitope in the hemagglutinin (HA) as a chimeric protein. Neutralizing antibodies specific for both RSV and influenza virus were induced by a single intranasal immunization of mice with PR8/RSV.HA-F. Mice that were immunized with PR8/RSV.HA-F were protected against RSV infection comparable with live RSV as evidenced by significant reduction of RSV lung viral loads, as well as the absence of lung eosinophilia and RSV-specific cellular immune responses. In contrast, formalin-inactivated RSV-immunized mice showed severe disease and high cellular immune responses in lungs after RSV infection. These findings support a concept that recombinant influenza virus carrying the RSV F243–294 neutralizing epitope can be developed as a promising RSV vaccine candidate which induces protective neutralizing antibodies but avoids lung immunopathology.

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“…There are several approaches including the insertion of foreign proteins into the surface glycoproteins HA 16-17 and NA 42-43 , and the manipulation of the nonstructural NS1 protein 44-45 or the PB2 protein 46-47 . In previous studies, we engineered influenza A viruses expressing a conserved domain of the RSV G protein or the RSV F 243-294 neutralizing epitope in the N-terminus of HA protein 14-15 .…”

Section: Discussionmentioning

confidence: 99%

Protection against respiratory syncytial virus by inactivated influenza virus carrying a fusion protein neutralizing epitope in a chimeric hemagglutinin

Lee

Hwang

Kim

et al. 2016

Nanomedicine: Nanotechnology, Biology and Medicine

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A desirable vaccine against respiratory syncytial virus (RSV) should induce neutralizing antibodies without eliciting abnormal T cell responses to avoid vaccine-enhanced pathology. In an approach to deliver RSV neutralizing epitopes without RSV-specific T cell antigens, we genetically engineered chimeric influenza virus expressing RSV F262-276 neutralizing epitopes in the globular head domain as a chimeric hemagglutinin (HA) protein. Immunization of mice with formalin-inactivated recombinant chimeric influenza/RSV F262-276 was able to induce RSV protective neutralizing antibodies and lower lung viral loads after challenge. Formalin-inactivated RSV immune mice showed high levels of pulmonary inflammatory cytokines, macrophages, IL-4-producing T cells, and extensive histopathology. However, RSV-specific T cell responses and enhancement of pulmonary histopathology were not observed after RSV infection of inactivated chimeric influenza/RSV F262-276. This study provides evidence that an inactivated vaccine platform of chimeric influenza/RSV virus can be developed into a safe RSV vaccine candidate without priming RSV-specific T cells and immunopathology.

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Influenza virus vaccine expressing fusion and attachment protein epitopes of respiratory syncytial virus induces protective antibodies in BALB/c mice

Cited by 19 publications

References 26 publications

Recombinant influenza virus carrying the conserved domain of respiratory syncytial virus (RSV) G protein confers protection against RSV without inflammatory disease

Recombinant influenza virus carrying the conserved domain of respiratory syncytial virus (RSV) G protein confers protection against RSV without inflammatory disease

Recombinant influenza virus expressing a fusion protein neutralizing epitope of respiratory syncytial virus (RSV) confers protection without vaccine-enhanced RSV disease

Protection against respiratory syncytial virus by inactivated influenza virus carrying a fusion protein neutralizing epitope in a chimeric hemagglutinin

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