Peptide-based candidate vaccine against respiratory syncytial virus

Yusibov, Vidadi; Mett, Vadim; Mett, Valentina; Davidson, Carley; Musiychuk, Konstantin; Gilliam, S.E.; Farese, Ann M.; MacVittie, Thomas J.; Mann, Dean L.

doi:10.1016/j.vaccine.2005.01.039

Cited by 70 publications

(34 citation statements)

References 15 publications

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“…Thus far, there has been no indication of a clear clinical vaccine success, either because (i) safety problems have surfaced, (ii) the immunogenicity of vaccines has been inadequate, or (iii) the studies have not reached completion. The challenge that remains is to strike an effective balance between the safety and immunogenicity of current RSV candidate vaccines [19][20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B

Zhan

Hurwitz

Krishnamurthy

et al. 2007

Vaccine

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The respiratory syncytial virus (RSV) is a serious pediatric pathogen for which there is currently no clinically-approved vaccine. This report describes the design and testing of a new RSV vaccine construct (rSV-RSV-F), created by the recombination of an RSV F sequence with the murine parainfluenza virus type 1 (Sendai virus, SV) genome. SV was selected as the vaccine backbone for this study, because it has previously been shown to elicit high-magnitude, durable immune activities in animal studies and has advanced to human safety trials as a xenogenic vaccine for human parainfluenza virus-type 1 (hPIV-1). Cells infected with the recombinant SV expressed RSV F protein, but F was not incorporated into progeny SV virions. When cotton rats were inoculated with the vaccine, high-titer RSV-binding and neutralizing antibodies were induced as well as interferon-γ-producing T-cells. Most striking was the protection against intra-nasal RSV challenge conferred by the vaccine. The rSV-RSV-F construct was also tested as a mixture with a second SV construct expressing the RSV G protein, but no clear advantage was demonstrated by combining the two vaccines. As a final analysis, the efficacy of the rSV-RSV-F vaccine was tested against an array of RSV isolates. Results showed that neutralizing and protective responses were effective against RSV isolates of both A and B subtypes. Together, experimental results encourage promotion of this recombinant SV construct as a vaccine candidate for the prevention of RSV in humans.

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Section: Introductionmentioning

confidence: 99%

Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B

Zhan

Hurwitz

Krishnamurthy

et al. 2007

Vaccine

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“…Previously, some HRSV epitopes that are restricted by different HLA class II molecules were identified using T cells from seropositive individuals (6 -9). However, these experiments were performed with overlapping synthetic pep-tides against only the F protein (6, 7) or a short fragment of 21 residues from the G protein (8). In contrast, only one published study attempted to elucidate the possible array of HRSV ligands that are restricted by HLA class II molecules in two different patients (9).…”

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confidence: 99%

Structural and Nonstructural Viral Proteins Are Targets of T-Helper Immune Response against Human Respiratory Syncytial Virus

Lorente

Barriga

Barnea

et al. 2016

Molecular & Cellular Proteomics

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Newly synthesized HLA class II molecules from antigenpresenting cells associate with the class II invariant chain (Ii). These complexes are eventually transported to specialized endosomal compartments where the Ii is progressively proteolyzed until only a fragment known as the class-II-associated invariant chain peptide (CLIP) 1 remains bound in the HLA class II peptide-binding groove to prevent it from binding to cellular peptides or pathogen peptides from the endogenous pathways. Interaction of HLA class II/CLIP complexes with the accessory molecule HLA-DM induces conformational changes in HLA class II molecules. Additionally, the release of CLIP results in peptide-receptive HLA class II molecules. This compartment fuses with a late endosome that contains exogenous proteins and/or viral particles that were previously endocytosed. Thus, the binding of antigen-processed peptides of different lengths, but with specific major anchor residues that can be deeply accommodated into specific pockets of the antigen recognition site of the HLA class II molecule, produces the stabilization of the nascent HLA class II/peptide complexes and allows for their subsequent transport to the cell membrane where they are exposed for T cell recognition (1).Human respiratory syncytial virus (HRSV) (2), which is included in the Paramyxoviridae family of the Mononegavirales order, presents a single-stranded, negative-sense RNA genome that codes for 11 proteins. This enveloped pneumovirus causes repeat infections throughout life, and although in healthy adults mild infections are generally reported, the health risk in infected pediatric, immunocompromised, and elderly populations is much more serious. HRSV is the main cause of hospitalization for bronchiolitis and pneumonia in infants and young children, with infection rates approaching 70% in the first year of life (3). Worldwide, at least 3.4 million hospital admissions each year are associated with severe HRSV disease, and the global mortality rate was estimated at more than a quarter of a million deaths in 2010, mainly in developing countries (4).The immune mechanisms involved in HRSV disease and protection are not completely understood; however, it is known that infection induces mucosal and systemic humoral and cellular responses. Studies evaluating CD4 ϩ and CD8 ϩ T-lymphocyte subsets individually or together showed that both effector MHC class I-and helper MHC class II-restricted cellular responses are particularly important in clearing infections (5). Previously, some HRSV epitopes that are restricted by different HLA class II molecules were identified using T cells from seropositive individuals (6 -9). However, these experiments were performed with overlapping synthetic pepFrom the ‡Centro Nacional

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“…Over the last few years, several experimental approaches aimed at developing an effective vaccine against RSV have been designed and assessed, such as attenuated RSV particles (14), recombinant viruses (different from RSV) that express RSV antigens (15)(16)(17), purified RSV proteins administered with bacterial adjuvants (17,18), RSV proteins packed as immune stimulating complexes (19), and RSV sequence peptides applied together with adjuvants (20). Although several RSV vaccine candidates may currently be at the end of their corresponding clinical trials around the world, most of these approaches unfortunately promise to be expensive to the point of being unaffordable for middle/low socioeconomic groups.…”

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confidence: 99%

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

Bueno

González

Cautivo

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

109

155

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Peptide-based candidate vaccine against respiratory syncytial virus

Cited by 70 publications

References 15 publications

Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B

Respiratory syncytial virus (RSV) fusion protein expressed by recombinant Sendai virus elicits B-cell and T-cell responses in cotton rats and confers protection against RSV subtypes A and B

Structural and Nonstructural Viral Proteins Are Targets of T-Helper Immune Response against Human Respiratory Syncytial Virus

Protective T cell immunity against respiratory syncytial virus is efficiently induced by recombinant BCG

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