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A bivalent influenza VLP vaccine confers complete inhibition of virus replication in lungs.

ABSTRACT: The conventional egg-grown influenza vaccines are trivalent. To test the feasibility of using multivalent influenza virus-like particles (VLPs) as an alternative influenza vaccine, we developed cell-derived influenza VLPs containing the hemagglutinin (HA) of the H1 subtype virus A/PR/8/34 or the H3 subtype virus A/Aichi/2/68 (X31). Mice immunized intramuscularly with bivalent influenza VLPs containing H1 and H3 HAs induced neutralizing activities against the homologous and closely related H1N1 strains A/PR/8/34 and A/WSN/33 as well as the H3N2 strains A/Aichi/2/68 (X31) and A/Hong Kong/68, but not the A/Philippines/2/82 strain isolated 14 years later. HA sequence and structure analysis indicated that antigenic distance could be a major factor in predicting cross-protection by VLP vaccines. The bivalent influenza VLP vaccine demonstrated advantages in broadening the protective immunity after lethal challenge infections when compared to a monovalent influenza VLP vaccine. High levels of the inflammatory cytokine IL-6 were observed in naïve or unprotected immunized mice but not in protected mice upon lethal challenge. These results indicate that multivalent influenza VLP vaccines can be an effective antigen for developing safe and alternative vaccine to control the spread of influenza viruses.

SUBMITTER: Quan FS

PROVIDER: S-EPMC5771410 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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A bivalent influenza VLP vaccine confers complete inhibition of virus replication in lungs.

Quan Fu Shi FS Steinhauer David D Huang Chunzi C Ross Ted M TM Compans Richard W RW Kang Sang-Moo SM

Vaccine 20080411 26

The conventional egg-grown influenza vaccines are trivalent. To test the feasibility of using multivalent influenza virus-like particles (VLPs) as an alternative influenza vaccine, we developed cell-derived influenza VLPs containing the hemagglutinin (HA) of the H1 subtype virus A/PR/8/34 or the H3 subtype virus A/Aichi/2/68 (X31). Mice immunized intramuscularly with bivalent influenza VLPs containing H1 and H3 HAs induced neutralizing activities against the homologous and closely related H1N1 s ...[more]

PMID: 18468740

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Project description:Abstract Background With the introduction of routine childhood rotavirus vaccination, norovirus is now becoming the major cause of medically-attended gastroenteritis in children. Takeda is developing a norovirus vaccine (NoV) that contains genotypes GI.1 and GII.4 consensus (GII.4c) sequence VLPs. We report the immunogenicity data of NoV administered to children from 6 months up to 4 years of age. Methods Two age cohorts (1 to < 4 years, and 6 to < 12 months, n = 120 per cohort) were enrolled in this ongoing double-blind, randomized, phase 2 dose-finding study conducted in Colombia and Panama. Children received one or two intramuscular doses of NoV formulations containing 15/15, 15/50, 50/50 or 50/150 ?g of GI.1/GII.4c VLPs adjuvanted with 0.5 mg Al(OH)3. Vaccinations were on Days 1 and 29, with saline placebo as dose two to maintain blinding in one dose groups. Antibody responses to each VLP were measured on days 1, 29 and 57 as functional histo-blood group binding antigen blocking antibodies (HBGA), expressed as seroresponse rates (SRR), the proportions displaying ? 4-fold increases over baseline, and geometric mean titres (GMT). Results Each formulation induced dosage-dependent HBGA responses after a single dose, with a further increase after a second dose. In 1- to <4 year-olds HBGA SRR against GI.1 and GII.4c after one dose were 55–62% and 67–82%, respectively. SRR increased to 93–100% and 83–100% after a second dose. In 6 to < 12 month-olds responses were lower after the first dose: SRRs were 10–61% and 17–65% for GI.1 and GII.4c, respectively, increasing to 83–100% and 80–92% after a second dose. GMTs reflected this pattern of responses with higher GMTs for GI.1 and GII.4c achieved with the 50/150 ?g formulation than the other dosages after both vaccinations in both age cohorts. Conclusion In 6–12 month-old infants and children up to 4 years of age, robust immune responses to the bivalent norovirus VLP vaccine candidates were observed; the highest HBGA responses in both age cohorts were observed after two doses of the 50/150 ?g formulation. Further clinical evaluation of these formulations is underway in infants < 6 months of age. Clinical Trial Registration (NCT: 02153112, EudraCT: 2014-000778-20) Disclosures T. Masuda, Takeda Pharmaceuticals International AG: Employee, Salary. I. Lefevre, Takeda Pharmaceuticals International AG: Employee, Salary. P. Mendelman, Takeda Pharmaceuticals International AG: Employee, Salary. J. Sherwood, Takeda Pharmaceuticals International AG: Employee, Salary. S. Bizjajeva, Takeda Pharmaceuticals International AG: Employee, Salary. A. Borkowski, Takeda Pharmaceuticals International AG: Employee, Salary.

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A bivalent influenza VLP vaccine confers complete inhibition of virus replication in lungs.

Publications

A bivalent influenza VLP vaccine confers complete inhibition of virus replication in lungs.

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