Antibodies to the Central Conserved Region of Respiratory Syncytial Virus (RSV) G Protein Block RSV G Protein CX3C-CX3CR1 Binding and Cross-Neutralize RSV A and B Strains

Choi, Youngjoo; Mason, Caleb S.; Jones, Les; Crabtree, Jackelyn; Jorquera, Patricia A.; Tripp, Ralph A.

doi:10.1089/vim.2011.0094

Cited by 49 publications

(59 citation statements)

References 69 publications

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“…This synthetic peptide induced a greater neutralizing antibody response to RSV than did the peptides flanking it (Choi et al 2012). These antibodies also inhibited G protein binding to CX3CR1 and reduced the effect of the G protein on lymphocyte migration.…”

Section: Vaccine Implicationsmentioning

confidence: 99%

Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins

McLellan

Ray

Peeples

2013

Current Topics in Microbiology and Immunology

228

280

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The two major glycoproteins on the surface of the RSV virion, the attachment glycoprotein (G) and the fusion (F) glycoprotein, control the initial phases of infection. G targets the ciliated cells of the airways, and F causes the virion membrane to fuse with a target cell membrane. The F protein is the major target for antiviral drug development, and both G and F glycoproteins are the antigens targeted by neutralizing antibodies induced by infection. In this chapter we review the structure and function of the RSV surface glycoproteins, including recent X-ray crystallographic data of the F glycoprotein in its pre- and postfusion conformations, and discuss how this information informs antigen selection and vaccine development.

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Section: Vaccine Implicationsmentioning

confidence: 99%

Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins

McLellan

Ray

Peeples

2013

Current Topics in Microbiology and Immunology

228

280

View full text Add to dashboard Cite

show abstract

“…Another advantage of the G protein as a vaccine candidate is the presence of neutralizing epitopes that are comparatively independent of protein structure. Several approaches, including subunit-, nanoparticle-, peptide-, and bacterial-based vaccines have been tried, and an mAb against G protein has been demonstrated to inhibit the virus infection in animal models (55)(56)(57)(58)(59)(60). However, the association of the G protein with VED indicates the need for caution during its development as an RSV vaccine (26).…”

mentioning

confidence: 99%

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

Zhou

Zhong

et al. 2016

The Journal of Immunology

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Respiratory syncytial virus (RSV) infection can cause severe disease in the lower respiratory tract of infants and older people. Vaccination with a formalin-inactivated RSV vaccine (FI-RSV) and subsequent RSV infection has led to mild to severe pneumonia with two deaths among vaccinees. The vaccine-enhanced disease (VED) was recently demonstrated to be due to an elevated level of Th2 cell responses following loss of regulatory T (Treg) cells from the lungs. To induce high levels of neutralizing Abs and minimize pathogenic T cell responses, we developed a novel strategy of immunizing animals with a recombinant RSV G protein together with cyclosporine A. This novel vaccine induced not only a higher level of neutralizing Abs against RSV infection, but, most importantly, also significantly higher levels of Treg cells that suppressed VED in the lung after RSV infection. The induced responses provided protection against RSV challenge with no sign of pneumonia or bronchitis. Treg cell production of IL-10 was one of the key factors to suppress VED. These finding indicate that G protein plus cyclosporine A could be a promising vaccine against RSV infection in children and older people.

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“…Tripp, Anderson, and colleagues have shown that antibodies specific to this CX3C sequence motif block the binding of G protein to the CX3C receptor, and that immunization with a peptide encoding the CX3C motif protected mice from RSV challenge and decreased pulmonary inflammation (Zhang et al 2010). These studies have recently been extended showing some cross reaction of antibodies raised to this region to RSV-B G protein in mice (Choi et al 2012) indicating that inclusion of this region of the G protein in vaccine candidates may increase protective responses to both RSV A and B.…”

Section: Peptide Vaccine Candidatesmentioning

confidence: 94%

Subunit and Virus-Like Particle Vaccine Approaches for Respiratory Syncytial Virus

Morrison

Walsh

2013

Current Topics in Microbiology and Immunology

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Despite its impact on global health, there is no vaccine available for the prevention of respiratory syncytial virus (RSV) infection. Failure to develop a licensed vaccine is not due to lack of effort, as numerous vaccine candidates have been characterized in preclinical and clinical studies spanning five decades. The vaccine candidates thus far explored can be generally divided into four categories: (1) whole inactivated virus, (2) replication competent, attenuated virus including recombinant viruses, (3) gene-based vectors, and (4) subunit and particulate forms of RSV antigens. The first clinically tested RSV vaccine candidate was a formalin-inactivated purified virus preparation administered to infants and children in the late 1960s. Due to the disastrous outcome of these trials and results of animal models investigating the mechanisms involved, there have been no further studies with inactivated RSV vaccines. Rather, efforts have focused on development of other approaches. In this chapter, we review the history and status of purified proteins, peptides, virus-like particles, virosomes, and nanoparticles and discuss their future potential.

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Antibodies to the Central Conserved Region of Respiratory Syncytial Virus (RSV) G Protein Block RSV G Protein CX3C-CX3CR1 Binding and Cross-Neutralize RSV A and B Strains

Cited by 49 publications

References 69 publications

Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins

Structure and Function of Respiratory Syncytial Virus Surface Glycoproteins

A Recombinant G Protein Plus Cyclosporine A–Based Respiratory Syncytial Virus Vaccine Elicits Humoral and Regulatory T Cell Responses against Infection without Vaccine-Enhanced Disease

Subunit and Virus-Like Particle Vaccine Approaches for Respiratory Syncytial Virus

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