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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

Immunogenicity of B epitopes.Total IgG antibody levels as measured by an ELISA in sera of C57BL/6 and BALB/c mice vaccinated with B epitopes, two weeks after booster vaccination. M2e specific antibodies in C57BL/6 mice (A) and BALB/c mice (B) and antibodies directed to HK-X31 in C57BL/6 mice (C) and BALB/c mice (D). IgG subtyping on M2e antibody responses showed that the addition of T epitopes had no negative effect in C57BL/6 mice (E) and BALB/c mice (F). When a Gaussian distribution was found data were analyzed with an unpaired t-test, which was the case for the BALB/c experiments. For C57BL/6 experiments a Mann-Whitney test was performed *p = <0.05, ****p = <0.0001.
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pone.0127969.g001: Immunogenicity of B epitopes.Total IgG antibody levels as measured by an ELISA in sera of C57BL/6 and BALB/c mice vaccinated with B epitopes, two weeks after booster vaccination. M2e specific antibodies in C57BL/6 mice (A) and BALB/c mice (B) and antibodies directed to HK-X31 in C57BL/6 mice (C) and BALB/c mice (D). IgG subtyping on M2e antibody responses showed that the addition of T epitopes had no negative effect in C57BL/6 mice (E) and BALB/c mice (F). When a Gaussian distribution was found data were analyzed with an unpaired t-test, which was the case for the BALB/c experiments. For C57BL/6 experiments a Mann-Whitney test was performed *p = <0.05, ****p = <0.0001.

Mentions: Evaluation of the B epitopes vaccine was performed in C57BL/6 and BALB/c mice. Sera collected 14 days post booster vaccination were analyzed by ELISA for HA2-specific and M2e-specific antibody responses, to determine whether immunization with B epitopes induced vaccine-specific antibodies. No HA2 responses were detected in an HA2-specific ELISA (data not shown). M2e-specific IgG antibodies, however, were detected in sera of C57BL/6 and BALB/c mice, proving the immunogenicity of the M2e B cell epitope (Fig 1A and 1B). To evaluate whether these antibodies could recognize the epitopes in their natural conformation, the sera were analyzed by ELISA for recognition of intact influenza virus. Specific antibodies in the serum of both C57BL/6 and BALB/c mice bound to the complete virus particles (Fig 1C and 1D). Therefore, antibodies induced by the vaccine are not only specific for the M2e peptide, but are also capable of recognizing the epitopes in their natural conformation, which is critical for a protective immune response.


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)

Immunogenicity of B epitopes.Total IgG antibody levels as measured by an ELISA in sera of C57BL/6 and BALB/c mice vaccinated with B epitopes, two weeks after booster vaccination. M2e specific antibodies in C57BL/6 mice (A) and BALB/c mice (B) and antibodies directed to HK-X31 in C57BL/6 mice (C) and BALB/c mice (D). IgG subtyping on M2e antibody responses showed that the addition of T epitopes had no negative effect in C57BL/6 mice (E) and BALB/c mice (F). When a Gaussian distribution was found data were analyzed with an unpaired t-test, which was the case for the BALB/c experiments. For C57BL/6 experiments a Mann-Whitney test was performed *p = <0.05, ****p = <0.0001.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4457525&req=5

pone.0127969.g001: Immunogenicity of B epitopes.Total IgG antibody levels as measured by an ELISA in sera of C57BL/6 and BALB/c mice vaccinated with B epitopes, two weeks after booster vaccination. M2e specific antibodies in C57BL/6 mice (A) and BALB/c mice (B) and antibodies directed to HK-X31 in C57BL/6 mice (C) and BALB/c mice (D). IgG subtyping on M2e antibody responses showed that the addition of T epitopes had no negative effect in C57BL/6 mice (E) and BALB/c mice (F). When a Gaussian distribution was found data were analyzed with an unpaired t-test, which was the case for the BALB/c experiments. For C57BL/6 experiments a Mann-Whitney test was performed *p = <0.05, ****p = <0.0001.
Mentions: Evaluation of the B epitopes vaccine was performed in C57BL/6 and BALB/c mice. Sera collected 14 days post booster vaccination were analyzed by ELISA for HA2-specific and M2e-specific antibody responses, to determine whether immunization with B epitopes induced vaccine-specific antibodies. No HA2 responses were detected in an HA2-specific ELISA (data not shown). M2e-specific IgG antibodies, however, were detected in sera of C57BL/6 and BALB/c mice, proving the immunogenicity of the M2e B cell epitope (Fig 1A and 1B). To evaluate whether these antibodies could recognize the epitopes in their natural conformation, the sera were analyzed by ELISA for recognition of intact influenza virus. Specific antibodies in the serum of both C57BL/6 and BALB/c mice bound to the complete virus particles (Fig 1C and 1D). Therefore, antibodies induced by the vaccine are not only specific for the M2e peptide, but are also capable of recognizing the epitopes in their natural conformation, which is critical for a protective immune response.

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