The path to an RSV vaccine

Shaw, Christine A.; Ciarlet, Max; Cooper, Brian; Dionigi, Lamberto; Keith, Paula; O’Brien, Kerry L.; Rafie-Kolpin, Maryam; Dormitzer, Philip R.

doi:10.1016/j.coviro.2013.05.003

Cited by 38 publications

(34 citation statements)

References 83 publications

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“…6 In the 50 y since then, multiple vaccine strategies have been investigated in preclinical and limited clinical settings. 7 These vaccines generally have not progressed to clinical evaluation or have been met with limited success in human trials. Progress has been hampered by limited immunogenicity, the induction of Th2-biased immunity, or unacceptable levels of adverse events.…”

Section: Introductionmentioning

confidence: 99%

Antibody response to respiratory syncytial virus infection in children <18 months old

Esposito

Scarselli²,

Lelii

et al. 2016

Human Vaccines & Immunotherapeutics

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The development of a safe and effective respiratory syncytial virus (RSV) vaccine might be facilitated by knowledge of the natural immune response to this virus. The aims of this study were to evaluate the neutralizing antibody response of a cohort of healthy children <18 months old to RSV infection. During the RSV season, 89 healthy children <18 months old were enrolled and followed up weekly for 12 weeks. At each visit, a nasopharyngeal swab was obtained for RSV detection by real-time polymerase chain reaction (PCR). During the study period, 2 blood samples were drawn and they were used to determine RSV geometric mean neutralizing antibody titres (GMT) against RSV. A total of 35 (39.3%) children had RSV detected during the study period. Among RSV-positive patients, children 7 months showed a significantly higher increase in antibody response (p<0.001). A significantly higher number of patients with a 4 -fold increase in GMT were 7 months old (p D 0.02) and presented lower respiratory tract infections (LRTIs) during the study period (p D 0.01). Viral shedding was longer among children aged 7 months (p D 0.06), those with viral load 10 6 copies/mL (p D 0.03), and those with LRTIs during the study period (p D 0.03), but it was not associated with the immune response (p D 0.41). In conclusion, natural RSV infection seems to evoke a low immune response in younger children. To be effective in this infant population, which is at highest risk of developing severe LRTIs, vaccines must be able to induce in the first months of life a stronger immune response than that produced by the natural infection.

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Section: Introductionmentioning

confidence: 99%

Antibody response to respiratory syncytial virus infection in children <18 months old

Esposito

Scarselli²,

Lelii

et al. 2016

Human Vaccines & Immunotherapeutics

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“…Unfortunately, the extremely high cost and administration logistics of palivizumab limit its use to patients in the developing world [1, 9,11]. Currently, the average cost of a 100 mg vial of palivizumab is $2,962 USD in the USA, and $1,505 CAD in Canada [33].…”

Section: Palivizumabmentioning

confidence: 99%

“…Due to the extremely infectious nature of the virus, it is estimated that most children become infected with RSV by the age of two [1,6]. Reinfections can occur repeatedly throughout life, often with mild upper respiratory tract (URT) symptoms in most healthy older children and adults [9][10][11]. Pre-term babies, newborn infants between 2 and 4 months of age, immunocompromised individuals, and the elderly are at highest risk of developing severe RSV disease [9,12].…”

mentioning

confidence: 99%

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

et al. 2016

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Respiratory syncytial virus (RSV) is the major causative agent of acute lower respiratory tract infections in infants and young children. Unfortunately, there are no licensed RSV vaccines available, and the few treatment options for high-risk individuals are either extremely costly or cause severe side effects and toxicity. Thus, the development of effective vaccines and therapeutic interventions against RSV is a preeminent public health priority.

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“…It is estimated that in 2005 hRSV was responsible for between 66,000-199,000 deaths worldwide in children younger than five years (111). There is currently no effective therapeutic or approved vaccine for hRSV and a strong desire exists within the scientific and medical communities to develop safe and effective treatments (58,59,114).…”

Section: Significancementioning

confidence: 99%

“…A vaccine is available for the amplifying host of HeV but measures remain in place to limit human exposure to HeV and NiV pending treatments for other livestock and humans (56). Importantly, effective vaccines for hRSV, hMPV and hPIV 3, which are substantial contributors to respiratory disease in children and immunocompromised individuals, remain elusive (57)(58)(59). Besides the serious risk of disease to humans, the paramyxoviruses HeV, NiV and NDV, also pose an economic threat through the infection of livestock.…”

Section: Taxonomy and Global Burdenmentioning

confidence: 99%

Structural characterisation of glycosylation of paramyxovirus attachment and fusion proteins by mass spectrometry

Pegg¹

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The family Paramyxoviridae (paramyxovirus) contains several significant human and animal pathogens.Represented within this family are human respiratory syncytial virus (hRSV) and Newcastle disease virus (NDV). The former contributes significantly to severe respiratory tract disease in infants, children and immunocompromised individuals. At present, highly efficacious therapeutics or safe and effective vaccines are not available for hRSV. NDV is the causative agent of Newcastle disease, afflicting a wide range of avian species. The desire to study NDV is due not only to the significant economic impact it has on the poultry industry worldwide, but also its potential use as an oncolytic agent and vaccine vector in humans and animals. Additionally, findings on NDV may be translated to closely related viruses that cause disease in humans, such as parainfluenza viruses.As outlined in Chapter 1 of this thesis, the infectious processes of all members of this family are driven by two major membrane glycoproteins whose ectodomains project from the viral envelope: the fusion (F) and attachment glycoproteins. The F glycoprotein is responsible for viral entry by means of fusion with host cell membranes while the variable attachment glycoproteins, haemagglutinin, haemagglutininneuraminidase (HN) and major surface glycoprotein (G), are involved in viral attachment to host cells.Previous studies have shown that altering the glycosylation profile of these proteins can modulate the ability of the virus to infect host cells and stimulate the host immune system. As yet, site-specific glycan heterogeneity of hRSV and NDV surface glycoproteins has not been defined at a chemical level. As described in Chapter 2, reverse-phase liquid chromatography tandem mass spectrometry (MS) strategies were implemented to characterise intact glycopeptides from the attachment and F glycoproteins of hRSV and NDV. Site-occupancy and monosaccharide compositions at a given site were determined using collision-induced dissociation, higher-energy collision dissociation, electron-transfer dissociation and electron-transfer dissociation combined with collision dissociation. As described in Chapter 3, a spectral processing program was developed called OxoExtract to aid identification of intact glycopeptides that were fragmented with higher-energy collision dissociation.The F and HN proteins of NDV were derived from virions propagated in embryonic eggs. Analyses of HN in Chapter 4 revealed high mannose N-linked glycans and complex or hybrid N-linked glycans that were variably fucosylated, sialylated and sulfated or phosphorylated. In total 63, 58, and 37 glycans were identified at sites N341, N433 and N481, respectively. In addition, a previously undocumented Olinked glycosylation site was identified in the stalk domain of the protein. Observed glycans from NDV F described in Chapter 5 were mainly high mannose, containing variations of five to nine mannose ii residues across four sites, N85, N191, N366 and N471. There was also evidence of fucosylated c...

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The path to an RSV vaccine

Cited by 38 publications

References 83 publications

Antibody response to respiratory syncytial virus infection in children <18 months old

Antibody response to respiratory syncytial virus infection in children <18 months old

Intranasal treatment with a novel immunomodulator mediates innate immune protection against lethal pneumonia virus of mice

Structural characterisation of glycosylation of paramyxovirus attachment and fusion proteins by mass spectrometry

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