Respiratory Syncytial Virus (RSV) G Protein Vaccines With Central Conserved Domain Mutations Induce CX3C-CX3CR1 Blocking Antibodies

Bergeron, Harrison C.; Murray, Jackelyn; Castrejon, Ana M Nuñez; DuBois, Rebecca M.; Tripp, Ralph A.

doi:10.3390/v13020352

Cited by 23 publications

(36 citation statements)

References 87 publications

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“…Moreover, several neutralising and protective antibodies have been isolated that target the CCD within RSV G [29][30][31][32]. Immunisation of mice with RSV G immunogens has also been shown to elicit antibodies capable of blocking the interaction of G with CX3CR1 [72], providing a rationale for inclusion of the CCD in vaccine designs. In this study, we extended the FxG strategy from NiV (Paramyxoviridae) to phylogenetically distinct RSV (Pneumoviridae).…”

Section: Discussionmentioning

confidence: 99%

Combinatorial F-G Immunogens as Nipah and Respiratory Syncytial Virus Vaccine Candidates

Isaacs

Cheung

Thakur

et al. 2021

Viruses

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Nipah virus (NiV) and respiratory syncytial virus (RSV) possess two surface glycoproteins involved in cellular attachment and membrane fusion, both of which are potential targets for vaccines. The majority of vaccine development is focused on the attachment (G) protein of NiV, which is the immunodominant target. In contrast, the fusion (F) protein of RSV is the main target in vaccine development. Despite this, neutralising epitopes have been described in NiV F and RSV G, making them alternate targets for vaccine design. Through rational design, we have developed a vaccine strategy applicable to phylogenetically divergent NiV and RSV that comprises both the F and G proteins (FxG). In a mouse immunization model, we found that NiV FxG elicited an improved immune response capable of neutralising pseudotyped NiV and a NiV mutant that is able to escape neutralisation by two known F-specific antibodies. RSV FxG elicited an immune response against both F and G and was able to neutralise RSV; however, this was inferior to the immune response of F alone. Despite this, RSV FxG elicited a response against a known protective epitope within G that is conserved across RSV A and B subgroups, which may provide additional protection in vivo. We conclude that inclusion of F and G antigens within a single design provides a streamlined subunit vaccine strategy against both emerging and established pathogens, with the potential for broader protection against NiV.

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Section: Discussionmentioning

confidence: 99%

Combinatorial F-G Immunogens as Nipah and Respiratory Syncytial Virus Vaccine Candidates

Isaacs

Cheung

Thakur

et al. 2021

Viruses

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“…To determine if probenecid treatment affected the anti-RSV antibody response, the sera from four female mice per group collected at days 7 pi were diluted (1:40) and assayed by ELISA using a modi ed protocol as described 44 . The ELISA detects both neutralizing and non-neutralizing antibodies and the use of RSV A2 lysate antigen provides a way to detect antibodies against multiple RSV proteins.…”

Section: Methodsmentioning

confidence: 99%

Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication

Murray¹,

Bergeron²,

Jones³

et al. 2022

Preprint

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RNA viruses like SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) are dependent on host genes for replication. We investigated if probenecid prophylaxis or treatment inhibited RSV replication in three epithelial cell lines used in RSV studies, i.e., Vero E6 cells, HEp-2 cells, and in primary normal human bronchoepithelial (NHBE) cells, and in BALB/c mice. The studies showed that nanomolar concentrations of all probenecid regimens prevent RSV strain A and RSV B replication in vitro and RSV strain A in vivo, representing a potential prophylactic and chemotherapeutic for RSV.

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“…Accumulating evidence has shown the protective benefits of G protein-mediated antibodies specifically regarding disease pathogenesis, thus G protein-based vaccines are being reconsidered [220]. Studies in mice have suggested that modification of the CX3C motif [221,222] and/or CCD [223] could elicit a safe and protective response and shift Th2-type responses to Th1-type or balanced responses. A G protein DNA vaccine (pVAX1/3G ) was shown to induce a Th1-type biased response and protect mice from the disease [224].…”

Section: Cd4+ T Cellsmentioning

confidence: 99%

Immunopathology of RSV: An Updated Review

Bergeron

Tripp

2021

Viruses

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RSV is a leading cause of respiratory tract disease in infants and the elderly. RSV has limited therapeutic interventions and no FDA-approved vaccine. Gaps in our understanding of virus–host interactions and immunity contribute to the lack of biological countermeasures. This review updates the current understanding of RSV immunity and immunopathology with a focus on interferon responses, animal modeling, and correlates of protection.

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Respiratory Syncytial Virus (RSV) G Protein Vaccines With Central Conserved Domain Mutations Induce CX3C-CX3CR1 Blocking Antibodies

Cited by 23 publications

References 87 publications

Combinatorial F-G Immunogens as Nipah and Respiratory Syncytial Virus Vaccine Candidates

Combinatorial F-G Immunogens as Nipah and Respiratory Syncytial Virus Vaccine Candidates

Probenecid Inhibits Respiratory Syncytial Virus (RSV) Replication

Immunopathology of RSV: An Updated Review

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