Conserved Synthetic Peptides from the Hemagglutinin of Influenza Viruses Induce Broad Humoral and T-Cell Responses in a Pig Model
Authors
Vergara-Alert, JuliaArgilaguet, Jordi M.
Busquets, Nuria
Ballester, Maria
Martin-Valls, Gerard E.
Rivas, Raquel
Lopez-Soria, Sergio
Solanes, David
Majo, Natalia
Segales, Joaquim
Veljković, Veljko
Rodriguez, Fernando
Darji, Ayub
Article
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Outbreaks involving either H5N1 or H1N1 influenza viruses (IV) have recently become an increasing threat to cause potential pandemics. Pigs have an important role in this aspect. As reflected in the 2009 human H1N1 pandemia, they may act as a vehicle for mixing and generating new assortments of viruses potentially pathogenic to animals and humans. Lack of universal vaccines against the highly variable influenza virus forces scientists to continuously design vaccines a la carte, which is an expensive and risky practice overall when dealing with virulent strains. Therefore, we focused our efforts on developing a broadly protective influenza vaccine based on the Informational Spectrum Method (ISM). This theoretical prediction allows the selection of highly conserved peptide sequences from within the hemagglutinin subunit 1 protein (HA1) from either H5 or H1 viruses which are located in the flanking region of the HA binding site and with the potential to elicit broader immune responses tha...n conventional vaccines. Confirming the theoretical predictions, immunization of conventional farm pigs with the synthetic peptides induced humoral responses in every single pig. The fact that the induced antibodies were able to recognize in vitro heterologous influenza viruses such as the pandemic H1N1 virus (pH1N1), two swine influenza field isolates (SwH1N1 and SwH3N2) and a H5N1 highly pathogenic avian virus, confirm the broad recognition of the antibodies induced. Unexpectedly, all pigs also showed T-cell responses that not only recognized the specific peptides, but also the pH1N1 virus. Finally, a partial effect on the kinetics of virus clearance was observed after the intranasal infection with the pH1N1 virus, setting forth the groundwork for the design of peptide-based vaccines against influenza viruses. Further insights into the understanding of the mechanisms involved in the protection afforded will be necessary to optimize future vaccine formulations.
Source:
PLOS One, 2012, 7, 7Funding / projects:
- Spanish Government [AGL2007-60434/GAN, AGL2010-22229-C03-01, RTA2010-00084-C02-02], Ministry of Science and Technological Development of the Republic of Serbia [143001], Spanish Ministry of Science and Innovation [BES-2008-00260]
DOI: 10.1371/journal.pone.0040524
ISSN: 1932-6203
PubMed: 22815759
WoS: 000306466100041
Scopus: 2-s2.0-84864008973
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VinčaTY - JOUR AU - Vergara-Alert, Julia AU - Argilaguet, Jordi M. AU - Busquets, Nuria AU - Ballester, Maria AU - Martin-Valls, Gerard E. AU - Rivas, Raquel AU - Lopez-Soria, Sergio AU - Solanes, David AU - Majo, Natalia AU - Segales, Joaquim AU - Veljković, Veljko AU - Rodriguez, Fernando AU - Darji, Ayub PY - 2012 UR - https://vinar.vin.bg.ac.rs/handle/123456789/4956 AB - Outbreaks involving either H5N1 or H1N1 influenza viruses (IV) have recently become an increasing threat to cause potential pandemics. Pigs have an important role in this aspect. As reflected in the 2009 human H1N1 pandemia, they may act as a vehicle for mixing and generating new assortments of viruses potentially pathogenic to animals and humans. Lack of universal vaccines against the highly variable influenza virus forces scientists to continuously design vaccines a la carte, which is an expensive and risky practice overall when dealing with virulent strains. Therefore, we focused our efforts on developing a broadly protective influenza vaccine based on the Informational Spectrum Method (ISM). This theoretical prediction allows the selection of highly conserved peptide sequences from within the hemagglutinin subunit 1 protein (HA1) from either H5 or H1 viruses which are located in the flanking region of the HA binding site and with the potential to elicit broader immune responses than conventional vaccines. Confirming the theoretical predictions, immunization of conventional farm pigs with the synthetic peptides induced humoral responses in every single pig. The fact that the induced antibodies were able to recognize in vitro heterologous influenza viruses such as the pandemic H1N1 virus (pH1N1), two swine influenza field isolates (SwH1N1 and SwH3N2) and a H5N1 highly pathogenic avian virus, confirm the broad recognition of the antibodies induced. Unexpectedly, all pigs also showed T-cell responses that not only recognized the specific peptides, but also the pH1N1 virus. Finally, a partial effect on the kinetics of virus clearance was observed after the intranasal infection with the pH1N1 virus, setting forth the groundwork for the design of peptide-based vaccines against influenza viruses. Further insights into the understanding of the mechanisms involved in the protection afforded will be necessary to optimize future vaccine formulations. T2 - PLOS One T1 - Conserved Synthetic Peptides from the Hemagglutinin of Influenza Viruses Induce Broad Humoral and T-Cell Responses in a Pig Model VL - 7 IS - 7 DO - 10.1371/journal.pone.0040524 ER -
@article{ author = "Vergara-Alert, Julia and Argilaguet, Jordi M. and Busquets, Nuria and Ballester, Maria and Martin-Valls, Gerard E. and Rivas, Raquel and Lopez-Soria, Sergio and Solanes, David and Majo, Natalia and Segales, Joaquim and Veljković, Veljko and Rodriguez, Fernando and Darji, Ayub", year = "2012", abstract = "Outbreaks involving either H5N1 or H1N1 influenza viruses (IV) have recently become an increasing threat to cause potential pandemics. Pigs have an important role in this aspect. As reflected in the 2009 human H1N1 pandemia, they may act as a vehicle for mixing and generating new assortments of viruses potentially pathogenic to animals and humans. Lack of universal vaccines against the highly variable influenza virus forces scientists to continuously design vaccines a la carte, which is an expensive and risky practice overall when dealing with virulent strains. Therefore, we focused our efforts on developing a broadly protective influenza vaccine based on the Informational Spectrum Method (ISM). This theoretical prediction allows the selection of highly conserved peptide sequences from within the hemagglutinin subunit 1 protein (HA1) from either H5 or H1 viruses which are located in the flanking region of the HA binding site and with the potential to elicit broader immune responses than conventional vaccines. Confirming the theoretical predictions, immunization of conventional farm pigs with the synthetic peptides induced humoral responses in every single pig. The fact that the induced antibodies were able to recognize in vitro heterologous influenza viruses such as the pandemic H1N1 virus (pH1N1), two swine influenza field isolates (SwH1N1 and SwH3N2) and a H5N1 highly pathogenic avian virus, confirm the broad recognition of the antibodies induced. Unexpectedly, all pigs also showed T-cell responses that not only recognized the specific peptides, but also the pH1N1 virus. Finally, a partial effect on the kinetics of virus clearance was observed after the intranasal infection with the pH1N1 virus, setting forth the groundwork for the design of peptide-based vaccines against influenza viruses. Further insights into the understanding of the mechanisms involved in the protection afforded will be necessary to optimize future vaccine formulations.", journal = "PLOS One", title = "Conserved Synthetic Peptides from the Hemagglutinin of Influenza Viruses Induce Broad Humoral and T-Cell Responses in a Pig Model", volume = "7", number = "7", doi = "10.1371/journal.pone.0040524" }
Vergara-Alert, J., Argilaguet, J. M., Busquets, N., Ballester, M., Martin-Valls, G. E., Rivas, R., Lopez-Soria, S., Solanes, D., Majo, N., Segales, J., Veljković, V., Rodriguez, F.,& Darji, A.. (2012). Conserved Synthetic Peptides from the Hemagglutinin of Influenza Viruses Induce Broad Humoral and T-Cell Responses in a Pig Model. in PLOS One, 7(7). https://doi.org/10.1371/journal.pone.0040524
Vergara-Alert J, Argilaguet JM, Busquets N, Ballester M, Martin-Valls GE, Rivas R, Lopez-Soria S, Solanes D, Majo N, Segales J, Veljković V, Rodriguez F, Darji A. Conserved Synthetic Peptides from the Hemagglutinin of Influenza Viruses Induce Broad Humoral and T-Cell Responses in a Pig Model. in PLOS One. 2012;7(7). doi:10.1371/journal.pone.0040524 .
Vergara-Alert, Julia, Argilaguet, Jordi M., Busquets, Nuria, Ballester, Maria, Martin-Valls, Gerard E., Rivas, Raquel, Lopez-Soria, Sergio, Solanes, David, Majo, Natalia, Segales, Joaquim, Veljković, Veljko, Rodriguez, Fernando, Darji, Ayub, "Conserved Synthetic Peptides from the Hemagglutinin of Influenza Viruses Induce Broad Humoral and T-Cell Responses in a Pig Model" in PLOS One, 7, no. 7 (2012), https://doi.org/10.1371/journal.pone.0040524 . .