Evaluation of a live, attenuated respiratory syncytial virus vaccine in infants

Wright, Peter F.; Shinozaki, Tatsuhiko; Fleet, William F.; Sell, Sarah H.; Thompson, Juliette; Karzon, David T.

doi:10.1016/s0022-3476(76)81044-x

Cited by 105 publications

(41 citation statements)

References 12 publications

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“…Furthermore, the mucosal route of vaccination is more resistant to the immunosuppressive effects of maternal antibodies than the parenteral route of administration [13,38]. Whilst it is possible to generate live, attenuated viruses by passage in cell culture, it has been difficult to produce a genetically stable HRSV with an appropriate balance between attenuation and immunogenicity [34,169]. Furthermore, we have increased the virulence of a BRSV isolate by sequential passage in gnotobiotic calves 8 .…”

Section: Prevention Control and Vaccinationmentioning

confidence: 99%

Bovine respiratory syncytial virus infection

Valarcher¹,

2007

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-Bovine respiratory syncytial virus (BRSV) belongs to the pneumovirus genus within the family Paramyxoviridae and is a major cause of respiratory disease in young calves. BRSV is enveloped and contains a negative sense, single-stranded RNA genome encoding 11 proteins. The virus replicates predominantly in ciliated respiratory epithelial cells but also in type II pneumocytes. It appears to cause little or no cytopathology in ciliated epithelial cell cultures in vitro, suggesting that much of the pathology is due to the host's response to virus infection. RSV infection induces an array of pro-inflammatory chemokines and cytokines that recruit neutrophils, macrophages and lymphocytes to the respiratory tract resulting in respiratory disease. Although the mechanisms responsible for induction of these chemokines and cytokines are unclear, studies on the closely related human (H)RSV suggest that activation of NF-κB via TLR4 and TLR3 signalling pathways is involved. An understanding of the mechanisms by which BRSV is able to establish infection and induce an inflammatory response has been facilitated by advances in reverse genetics, which have enabled manipulation of the virus genome. These studies have demonstrated an important role for the non-structural proteins in anti-interferon activity, a role for a virokinin, released during proteolytic cleavage of the fusion protein, in the inflammatory response and a role for the SH and the secreted form of the G protein in establishing pulmonary infection. Knowledge gained from these studies has also provided the opportunity to develop safe, stable, live attenuated virus vaccine candidates.

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Section: Prevention Control and Vaccinationmentioning

confidence: 99%

Bovine respiratory syncytial virus infection

Valarcher¹,

2007

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Section: Introductionmentioning

confidence: 99%

“…A formalin-inactivated virus vaccine tested approximately 20 years ago failed to prevent infection, and actually increased the severity of disease upon subsequent RSV infection (Kim et al, 1969). Temperature-sensitive mutants have also failed as vaccines because of either insufficient attenuation or loss of immunogenicity (Kim et al, 1971 ;Wright et al, 1982).Work using purified RSV proteins from RSV-infected cells (Walsh et al, 1987), or vaccination with vaccinia virus recombinants containing the F (fusion) or G (attachment) glycoprotein in mice (Stott et al, 1986;Wertz et al, 1987) or rats (Olmsted et al, 1986; resulted in the induction of neutralizing antibody and in a significant reduction in the replication of RSV in lung tissue. Our previous work (Wathen et al, 1989a) demonstrated that vaccination with a secreted form of the F glycoprotein (Ft), expressed in insect cells using a baculovirus vector also resulted in induction of neutralizing antibody, and in significant reduction in the titre of RSV recovered from cotton rats.…”

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confidence: 99%

Protection of Cotton Rats against Human Respiratory Syncytial Virus by Vaccination with a Novel Chimeric FG Glycoprotein

Brideau

Walters

Stier

et al. 1989

Journal of General Virology

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SUMMARYThe cotton rat model of experimental human respiratory syncytial virus (RSV) infection was used to study the efficacy of FG, a novel chimeric glycoprotein which was expressed in insect cells using a baculovirus vector. FG contained the extracellular regions of the F (fusion) and G (attachment) glycoproteins of RSV. Vaccination with FG resulted in induction of neutralizing antibody and was correlated with protection of lung tissue from RSV challenge against both serogroup A and B virus strains. Both crude FG taken from supernatants of insect cells and affinity-purified FG were immunogenic and active against RSV. FG vaccination was effective by three routes of administration, following a single dose, and when administered with different adjuvants. INTRODUCTIONHuman respiratory syncytial virus (RSV), a paramyxovirus, is the major cause of severe lower respiratory disease in children under 1 year of age (Parrott et al., 1973). Previous attempts to produce a safe and effective vaccine against RSV have failed. A formalin-inactivated virus vaccine tested approximately 20 years ago failed to prevent infection, and actually increased the severity of disease upon subsequent RSV infection (Kim et al., 1969). Temperature-sensitive mutants have also failed as vaccines because of either insufficient attenuation or loss of immunogenicity (Kim et al., 1971 ;Wright et al., 1982).Work using purified RSV proteins from RSV-infected cells (Walsh et al., 1987), or vaccination with vaccinia virus recombinants containing the F (fusion) or G (attachment) glycoprotein in mice (Stott et al., 1986;Wertz et al., 1987) or rats (Olmsted et al., 1986; resulted in the induction of neutralizing antibody and in a significant reduction in the replication of RSV in lung tissue. Our previous work (Wathen et al., 1989a) demonstrated that vaccination with a secreted form of the F glycoprotein (Ft), expressed in insect cells using a baculovirus vector also resulted in induction of neutralizing antibody, and in significant reduction in the titre of RSV recovered from cotton rats. The Ft glycoprotein contained the majority of the extracellular region of F (amino acids 1 to 489), but was missing the anchor region of the glycoprotein.In the preceding paper (Wathen et al., 1989b), we described a novel chimeric glycoprotein of RSV termed FG, which was expressed in insect cells using a baculovirus vector. This glycoprotein contained the signal and extracellular regions of the F glycoprotein linked to the extracellular region of the G glycoprotein. We now report that vaccination of cotton rats with the chimeric FG glycoprotein resulted in the induction of high titres of neutralizing antibody and in protection from challenge with either serogroup A or B strains of RSV. In addition, we describe the effect of route and frequency of vaccination, and the use of adjuvants on the efficacy of FG.

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“…Efforts at preventing RS viral infections using conventional vaccines, either temperature-sensitive mutants (Wright et al, 1982) or formalin-inactivated preparations of concentrated virus (Fulginiti et al, 1969;Kapikian et al, 1969;Kim et al, 1969), were abandoned because protection was inadequate or because vaccinees developed more severe disease following their next natural infection. More recently, perhaps in response to the vaccine failures, research has focused on elucidating the roles of viral proteins in eliciting protective humoral and cell-mediated immunity to RS virus.…”

Section: Introductionmentioning

confidence: 99%

Appearance of a Soluble Form of the G Protein of Respiratory Syncytial Virus in Fluids of Infected Cells

Hendricks¹,

Baradaran²,

McIntosh³

et al. 1987

Journal of General Virology

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SUMMARYWe examined the antigenic reactivities and virion associations of glycoproteins that were released into the culture fluids of cells infected with respiratory syncytial (RS) virus. Culture fluids and cell extracts were obtained from cells 24 to 30 h after they were infected with the Long strain of RS virus. Radioimmune precipitation of [3H]glucosamine-labelled glycoproteins by large glycoprotein (G)-specific or fusion protein (F)-specific monoclonal antibodies (MAbs) revealed that the G, F1 and F2 proteins were present in cell extracts but only the G protein was clearly evident in culture fluids. A glycoprotein (Mr 43K) which may be a precursor or a breakdown product of the G protein was also precipitated by the G-specific MAb from cell extracts and culture fluids. The G protein in culture fluids was slightly smaller (Mr 82K) than the G protein in cell extracts (Mr 88K). An abundant or heavily labelled, 18K glycoprotein in the fluids of virus-infected but not of mock-infected cells was weakly precipitated by the Fspecific MAb; this suggested that the 18K protein shares epitopes with the fusion protein of RS virus. The absence of F1 and F 2 polypeptides from culture fluids is evidence that the cells, which contained an abundance of these proteins, were intact. To determine whether any of the viral glycoproteins released by infected cells were soluble (non-virion-associated), culture fluid was subjected to rate zonal centrifugation in a 10 to 50~ sucrose gradient. An assay of fractions using a MAb-capture ELISA for the nucleocapsid (N) and F proteins revealed a peak of activity, due to virions, in the centre of the gradient, and a strong signal for the N protein at the top of the gradient suggesting that N protein was released from intact cells. Radioimmune precipitation of glycoproteins from the fractions at the top of the gradient using a hyperimmune guineapig serum revealed the G protein and a heterogeneous band which had the electrophoretic mobility of the 43K protein. Neither the F~ nor the F 2 protein was present in these fractions thus suggesting that virions had remained intact. These results showed that a soluble form of the G protein of RS virus is released into the culture fluids of intact, infected cells. Several theories concerning viral and non-viral origins for the 18K protein are discussed.

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Evaluation of a live, attenuated respiratory syncytial virus vaccine in infants

Cited by 105 publications

References 12 publications

Bovine respiratory syncytial virus infection

Bovine respiratory syncytial virus infection

Protection of Cotton Rats against Human Respiratory Syncytial Virus by Vaccination with a Novel Chimeric FG Glycoprotein

Appearance of a Soluble Form of the G Protein of Respiratory Syncytial Virus in Fluids of Infected Cells

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