Formulation of the purified fusion protein of respiratory syncytial virus with the saponin QS-21 induces protective immune responses in mice that are similar to those generated by experimental infection

Hancock, Gerald E.; Speelman, Dan J.; Frenchick, P.J.; Mineo-Kuhn, Michelle M.; Baggs, Raymond B.; Hahn, Denise J.

doi:10.1016/0264-410x(95)98263-a

Cited by 83 publications

(49 citation statements)

References 38 publications

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“…Purified Quillaia saponin fractions, in free form or incorporated into ISCOMs also induce CTL responses in mice. This has been reported for influenzaISCOMs containing ISCOPREP 703 [14] and QS-21 formulated with OVA [112], HIV gp160 [113], HIV-1 gp160 peptides [114], recombinant human CMV glycoprotein B [115], RSV F protein [116], and ras-expressing tumor cells [117]. SIV envelope glycoprotein (Env) and p27gag protein in ISCOMs and SIV proteins formulated with QS-21 induced CTL activity in non-human primates [118,119].…”

Section: Activation Of Ctl Responsesmentioning

confidence: 74%

ISCOMs: an adjuvant with multiple functions

Sjölander

Cox

Barr

1998

Journal of Leukocyte Biology

158

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Section: Activation Of Ctl Responsesmentioning

confidence: 74%

ISCOMs: an adjuvant with multiple functions

Sjölander

Cox

Barr

1998

Journal of Leukocyte Biology

158

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“…Eosinophilia was dependent on the presence of IL-5 and CD4 ϩ T cells. In contrast, vaccination with vaccinia virus-expressed F protein (17,40) or with natural F protein mixed with an appropriate adjuvant (22) did not prime for eosinophilia. Recently it was reported that PBMC from most human volunteers readily recognized epitopes located within the central ectodomain encompassed by amino acids 149 to 200 of G protein (20).…”

mentioning

confidence: 82%

“…Infectious virus titers in culture supernatants or lungs after experimental infection or challenge were determined by a plaque assay using HEp-2 cell monolayers as previously described (22,23). The sensitivities of mutant viruses to temperature were determined at 32, 37, 39, and 40°C (13).…”

Section: Vol 78 2004mentioning

confidence: 99%

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Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Elliott¹,

Pryharski²,

et al. 2004

J Virol

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It is essential that preventative vaccines for respiratory syncytial virus (RSV) elicit balanced T-cell responses. Immune responses dominated by type 2 T cells against RSV antigens are believed to cause exaggerated respiratory tract disease and may also contribute to unwanted inflammation in the airways that predisposes infants to wheeze through adolescence. Here we report on the construction and characterization of recombinant RSV (rRSV) strains with amino acids 151 to 221 or 178 to 219 of the attachment (G) glycoprotein deleted (rA2cp⌬G150-222 or rA2cp⌬G177-220, respectively). The central ectodomain was chosen for modification because a peptide spanning amino acids 149 to 200 of G protein has recently been shown to prime several strains of naïve inbred mice for polarized type 2 T-cell responses, and peripheral blood T cells from most human donors recognize epitopes within this region. Quantitative PCR demonstrated that synthesis of nascent rRSV genomes in human lung epithelial cell lines was similar to that for the parent virus (cp-RSV). Plaque assays further indicated that rRSV replication was not sensitive to 37°C, but pinpoint morphology was observed at 39°C. Both rRSV strains replicated in the respiratory tracts of BALB/c mice and elicited serum neutralization and anti-F-protein immunoglobulin G titers that were equivalent to those elicited by cp-RSV and contributed to a 3.9-log 10 -unit reduction in RSV A2 levels 4 days after challenge. Importantly, pulmonary eosinophilia was significantly diminished in BALB/c mice primed with native G protein and challenged with either rA2cp⌬G150-222 or rA2cp⌬G177-220. These findings are important for the development of attenuated RSV vaccines.

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“…A variety of adjuvants are available; one of these is QS21, a purified saponin from the bark of the South American tree, Quillaja saponaria (4). QS21 adjuvant is known as a T helper 1 cell adjuvant that enhances both humoral and cell mediated immune responses (4)(5)(6). Preclinical studies by us in mice comparing aqueous IVV to IVV containing the adjuvants QS21, monophosphoryl lipid A (MPL), or incomplete Freund's adjuvant (IFA) revealed that QS21 was superior for inducing antibody responses and protection in both unprimed and primed mice (7).…”

Section: Introductionmentioning

confidence: 99%

Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant

Mbawuike¹,

Zang²,

Couch³

2007

Vaccine

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To evaluate humoral (antibody) and cell mediated immune (CMI) responses, 30 healthy young adults were either given inactivated influenza vaccine with or without QS21 adjuvant. Vaccination site pain and postvaccination myalgias were greater in the QS21 group. Serum antibody increases occurred in 73 to 93% of subjects for each vaccine and antigen at 2 weeks and 4 weeks but frequencies and mean titers for the two vaccines were not different. No differences in T cell cytotoxicity were detected for either vaccine for influenza A or B infected cells. IFN-γ for both vaccine groups was increased in supernates after 3 days but not 7 days of stimulation in the cytotoxicity tests; amounts for the two vaccines were similar. To further evaluate CMI, remaining PBMCs were stimulated overnight with cells infected with each vaccine strain; an increase in spot forming cells (sfc) for Granzyme B and IFN-γ was found for all subjects and in 51 of 54 sfc tests. A slightly higher response in the Gran B test for QS21 subjects was suggested, but no clear immune response advantage was identified among healthy adults for QS21 adjuvanted influenza vaccine.

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Formulation of the purified fusion protein of respiratory syncytial virus with the saponin QS-21 induces protective immune responses in mice that are similar to those generated by experimental infection

Cited by 83 publications

References 38 publications

ISCOMs: an adjuvant with multiple functions

ISCOMs: an adjuvant with multiple functions

Characterization of Recombinant Respiratory Syncytial Viruses with the Region Responsible for Type 2 T-Cell Responses and Pulmonary Eosinophilia Deleted from the Attachment (G) Protein

Humoral and cell-mediated immune responses of humans to inactivated influenza vaccine with or without QS21 adjuvant

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