Immunization of cotton rats with the fusion (F) and large (G) glycoproteins of respiratory syncytial virus (RSV) protects against RSV challenge without potentiating RSV disease

Murphy, B R; Sotnikov, Alex V.; Pr, Paradiso; Sw, Hildreth; Ab, Jenson; Rb, Baggs; Lawrence, Lisa; Jj, Zubak; Chanock, R. M.; Beeler, JA

doi:10.1016/0264-410x(89)90278-8

Cited by 102 publications

(54 citation statements)

References 18 publications

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“…The F protein has been shown to be most effective at inducing neutralizing antibodies and protective immunity in animal models (13, 14, 38, 52, 53, 58). The G protein also induces neutralizing antibodies and protective immunity (4,25,28,36,47,49,51), but it has features that contribute to RSV disease pathogenesis (5,12,29,41,54). One region in the RSV G protein contains a CX3C chemokine motif capable of binding to CX3CR1 and antagonizing the activities of CX3CL1 (56).…”

Section: Discussionmentioning

confidence: 99%

Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice

Zhang

Choi

Haynes

et al. 2010

J Virol

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Respiratory syncytial virus (RSV) infection causes substantial morbidity and some deaths in the young and elderly worldwide. There is no safe and effective vaccine available, although it is possible to reduce the hospitalization rate for high-risk children by anti-RSV antibody prophylaxis. RSV has been shown to modify the immune response to infection, a feature linked in part to RSV G protein CX3C chemokine mimicry. This study determined if vaccination with G protein polypeptides or peptides spanning the central conserved region of the G protein could induce antibodies that blocked G protein CX3C-CX3CR1 interaction and disease pathogenesis mediated by RSV infection. The results show that mice vaccinated with G protein peptides or polypeptides containing the CX3C motif generate antibodies that inhibit G protein CX3C-CX3CR1 binding and chemotaxis, reduce lung virus titers, and prevent body weight loss and pulmonary inflammation. The results suggest that RSV vaccines that induce antibodies that block G protein CX3C-CX3CR1 interaction may offer a new, safe, and efficacious RSV vaccine strategy.

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Section: Discussionmentioning

confidence: 99%

Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice

Zhang

Choi

Haynes

et al. 2010

J Virol

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“…Clinical trials with purified F protein (PFP) subunit vaccines and live attenuated vaccines have been evaluated (39,42,44,45,63,84). PFP vaccines were promising vaccine candidates for the elderly and for RSV-seropositive children with underlying pulmonary disease because vaccination studies in the rodent model showed that the F protein vaccination was associated with decreased viral titers, overall reduced disease burden, and minor pathology following RSV challenge (43,85,86). However, PFP vaccines did not provide sufficient RSV neutralizing antibodies in seronegative chimpanzees that received three doses, and thus the studies were halted (87).…”

Section: Discussionmentioning

confidence: 99%

A Novel Influenza Virus Hemagglutinin-Respiratory Syncytial Virus (RSV) Fusion Protein Subunit Vaccine against Influenza and RSV

Turner

Jones

Tompkins

et al. 2013

J Virol

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Influenza A virus and respiratory syncytial virus (RSV) cause substantial morbidity and mortality afflicting the ends of the age spectrum during the autumn through winter months in the United States. The benefit of vaccination against RSV and influenza using a subunit vaccine to enhance immunity and neutralizing antibody was investigated. Influenza virus hemagglutinin (HA) and RSV fusion (F) protein were tested as vaccine components alone and in combination to explore the adjuvant properties of RSV F protein on HA immunity. Mice vaccinated with HA and F exhibited robust immunity that, when challenged, had reduced viral burden for both influenza and RSV. These studies show an enhancing and cross-protective benefit of F protein for anti-HA immunity.

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“…However, several RSV-derived proteins and their derivatives have been evaluated in preclinical and clinical stages as subunit vaccines. Although purified F and G proteins from RSV-infected cultures and F/G chimeric proteins produced by a baculovirus expression system generate antibody responses similar to those observed upon FI-RSV vaccination in rodent models (39,40), the appropriate use of adjuvants could improve immunogenicity and diminish the adverse effects of subunit vaccines (41,42). The purified F protein series (PFP-1, 2 and 3) has been tested in several clinical trials, showing promising results with no obvious adverse events and more than a 4-fold increase in neutralizing antibody titer in the majority of subjects (43)(44)(45).…”

Section: Current Rsv Vaccine Strategiesmentioning

confidence: 99%

Current progress on development of respiratory syncytial virus vaccine

Chang

2011

BMB Reports

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Immunization of cotton rats with the fusion (F) and large (G) glycoproteins of respiratory syncytial virus (RSV) protects against RSV challenge without potentiating RSV disease

Cited by 102 publications

References 18 publications

Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice

Vaccination To Induce Antibodies Blocking the CX3C-CX3CR1 Interaction of Respiratory Syncytial Virus G Protein Reduces Pulmonary Inflammation and Virus Replication in Mice

A Novel Influenza Virus Hemagglutinin-Respiratory Syncytial Virus (RSV) Fusion Protein Subunit Vaccine against Influenza and RSV

Current progress on development of respiratory syncytial virus vaccine

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