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Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets.

Rosendahl Huber SK, Camps MG, Jacobi RH, Mouthaan J, van Dijken H, van Beek J, Ossendorp F, de Jonge J - PLoS ONE (2015)

Bottom Line: Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice.Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination.Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.

View Article: PubMed Central - PubMed

Affiliation: Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

ABSTRACT
Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.

No MeSH data available.


Related in: MedlinePlus

Virological analysis of lungs and trachea of ferrets.Five days after challenge ferrets were sacrificed and virus titers in the lungs and trachea were determined by end point titration. Depicted are log transformed titers in the lungs (A) and trachea (B). Ferrets that had to be sacrificed or died prior to scheduled section were excluded from the analysis. Data were analyzed by the Mann-Whitney test.*p = <0.05 **p = <0.01 compared to mock vaccinated mice.
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pone.0127969.g006: Virological analysis of lungs and trachea of ferrets.Five days after challenge ferrets were sacrificed and virus titers in the lungs and trachea were determined by end point titration. Depicted are log transformed titers in the lungs (A) and trachea (B). Ferrets that had to be sacrificed or died prior to scheduled section were excluded from the analysis. Data were analyzed by the Mann-Whitney test.*p = <0.05 **p = <0.01 compared to mock vaccinated mice.

Mentions: Fig 6A shows viral titers in the lungs. A significant difference is observed between the ferrets vaccinated i.m. with the 25 SLP + B epitopes and the corresponding negative control ferrets. Fig 6B shows viral load in the trachea, in which there is a significant difference observed between both the i.m. and i.n. 25 SLP + B epitopes vaccinated ferrets and their corresponding controls. The positive control ferret had no detectable virus titers in the lungs, but some virus remained detectable in the trachea. These results show that, depending on the route of immunization, the 25 SLP + B epitopes are capable of reducing virus load in both the lungs and the trachea of ferrets. Concluding, although vaccination of ferrets with the 25 SLP + B epitopes did not significantly ease symptoms of influenza virus challenge, the vaccine is capable of reducing virus titers in the lungs and trachea, which is especially of relevance from a transmission point of view.


Synthetic Long Peptide Influenza Vaccine Containing Conserved T and B Cell Epitopes Reduces Viral Load in Lungs of Mice and Ferrets.

Rosendahl Huber SK, Camps MG, Jacobi RH, Mouthaan J, van Dijken H, van Beek J, Ossendorp F, de Jonge J - PLoS ONE (2015)

Virological analysis of lungs and trachea of ferrets.Five days after challenge ferrets were sacrificed and virus titers in the lungs and trachea were determined by end point titration. Depicted are log transformed titers in the lungs (A) and trachea (B). Ferrets that had to be sacrificed or died prior to scheduled section were excluded from the analysis. Data were analyzed by the Mann-Whitney test.*p = <0.05 **p = <0.01 compared to mock vaccinated mice.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4457525&req=5

pone.0127969.g006: Virological analysis of lungs and trachea of ferrets.Five days after challenge ferrets were sacrificed and virus titers in the lungs and trachea were determined by end point titration. Depicted are log transformed titers in the lungs (A) and trachea (B). Ferrets that had to be sacrificed or died prior to scheduled section were excluded from the analysis. Data were analyzed by the Mann-Whitney test.*p = <0.05 **p = <0.01 compared to mock vaccinated mice.
Mentions: Fig 6A shows viral titers in the lungs. A significant difference is observed between the ferrets vaccinated i.m. with the 25 SLP + B epitopes and the corresponding negative control ferrets. Fig 6B shows viral load in the trachea, in which there is a significant difference observed between both the i.m. and i.n. 25 SLP + B epitopes vaccinated ferrets and their corresponding controls. The positive control ferret had no detectable virus titers in the lungs, but some virus remained detectable in the trachea. These results show that, depending on the route of immunization, the 25 SLP + B epitopes are capable of reducing virus load in both the lungs and the trachea of ferrets. Concluding, although vaccination of ferrets with the 25 SLP + B epitopes did not significantly ease symptoms of influenza virus challenge, the vaccine is capable of reducing virus titers in the lungs and trachea, which is especially of relevance from a transmission point of view.

Bottom Line: Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice.Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination.Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.

View Article: PubMed Central - PubMed

Affiliation: Centre for Infectious Disease Control (Cib), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.

ABSTRACT
Currently licensed influenza vaccines mainly induce antibodies against highly variable epitopes. Due to antigenic drift, protection is subtype or strain-specific and regular vaccine updates are required. In case of antigenic shifts, which have caused several pandemics in the past, completely new vaccines need to be developed. We set out to develop a vaccine that provides protection against a broad range of influenza viruses. Therefore, highly conserved parts of the influenza A virus (IAV) were selected of which we constructed antibody and T cell inducing peptide-based vaccines. The B epitope vaccine consists of the highly conserved HA2 fusion peptide and M2e peptide coupled to a CD4 helper epitope. The T epitope vaccine comprises 25 overlapping synthetic long peptides of 26-34 amino acids, thereby avoiding restriction for a certain MHC haplotype. These peptides are derived from nucleoprotein (NP), polymerase basic protein 1 (PB1) and matrix protein 1 (M1). C57BL/6 mice, BALB/c mice, and ferrets were vaccinated with the B epitopes, 25 SLP or a combination of both. Vaccine-specific antibodies were detected in sera of mice and ferrets and vaccine-specific cellular responses were measured in mice. Following challenge, both mice and ferrets showed a reduction of virus titers in the lungs in response to vaccination. Summarizing, a peptide-based vaccine directed against conserved parts of influenza virus containing B and T cell epitopes shows promising results for further development. Such a vaccine may reduce disease burden and virus transmission during pandemic outbreaks.

No MeSH data available.


Related in: MedlinePlus