TY  - JOUR
AU  - Sistere-Oro, Marta
AU  - Vergara-Alert, Julia
AU  - Stratmann, Thomas
AU  - Lopez-Serrano, Sergi
AU  - Pina-Pedrero, Sonia
AU  - Cordoba, Lorena
AU  - Perez-Maillo, Monica
AU  - Pleguezuelos, Patricia
AU  - Vidal, Enric
AU  - Veljković, Veljko
AU  - Segalés, Joaquim
AU  - Nielsen, Jens Peter
AU  - Fomsgaard, Anders
AU  - Darji, Ayub
AU  - Huber, Victor C.
PY  - 2019
UR  - http://dx.plos.org/10.1371/journal.pone.0212431
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/8083
AB  - Swine influenza viruses (SIVs), the causal agents of swine influenza, are not only important to control due to the economic losses in the swine industry, but also can be pandemic pathogens. Vaccination is one of the most relevant strategies to control and prevent influenza infection. Current human vaccines against influenza induce strain-specific immunity and annual update is required due to the virus antigenic shift phenomena. Previously, our group has reported the use of conserved hemagglutinin peptides (HA-peptides) derived from H1-influenza virus as a potential multivalent vaccine candidate. Immunization of swine with these HA-peptides elicited antibodies that recognized and neutralized heterologous influenza viruses in vitro and demonstrated strong hemagglutination-inhibiting activity. In the present work, we cloned one HA-peptide (named NG34) into a plasmid fused with cytotoxic T lymphocyte-associated antigen (CTLA4) which is a molecule that modifies T cell activation and with an adjuvant activity interfering with the adaptive immune response. The resulting plasmid, named pCMV-CTLA4-Ig-NG34, was administered twice to animals employing a needle-free delivery approach. Two studies were carried out to test the efficacy of pCMV-CTLA4-Ig-NG34 as a potential swine influenza vaccine, one in seronegative and another in seropositive pigs against SIV. The second one was aimed to evaluate whether pCMV-CTLA4-Ig-NG34 vaccination would overcome maternally derived antibodies (MDA). After immunization, all animals were intranasally challenged with an H3N2 influenza strain. A complete elimination or significant reduction in the viral shedding was observed within the first week after the challenge in the vaccinated animals from both studies. In addition, no challenged heterologous virus load was detected in the airways of vaccinated pigs. Overall, it is suggested that the pCMV-CTLA4-Ig-NG34 vaccine formulation could potentially be used as a multivalent vaccine against influenza viruses. © 2019 Sisteré-Oró et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
T2  - PLOS One
T1  - Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge
VL  - 14
IS  - 3
SP  - e0212431
DO  - 10.1371/journal.pone.0212431
ER  - 

@article{
author = "Sistere-Oro, Marta and Vergara-Alert, Julia and Stratmann, Thomas and Lopez-Serrano, Sergi and Pina-Pedrero, Sonia and Cordoba, Lorena and Perez-Maillo, Monica and Pleguezuelos, Patricia and Vidal, Enric and Veljković, Veljko and Segalés, Joaquim and Nielsen, Jens Peter and Fomsgaard, Anders and Darji, Ayub and Huber, Victor C.",
year = "2019",
abstract = "Swine influenza viruses (SIVs), the causal agents of swine influenza, are not only important to control due to the economic losses in the swine industry, but also can be pandemic pathogens. Vaccination is one of the most relevant strategies to control and prevent influenza infection. Current human vaccines against influenza induce strain-specific immunity and annual update is required due to the virus antigenic shift phenomena. Previously, our group has reported the use of conserved hemagglutinin peptides (HA-peptides) derived from H1-influenza virus as a potential multivalent vaccine candidate. Immunization of swine with these HA-peptides elicited antibodies that recognized and neutralized heterologous influenza viruses in vitro and demonstrated strong hemagglutination-inhibiting activity. In the present work, we cloned one HA-peptide (named NG34) into a plasmid fused with cytotoxic T lymphocyte-associated antigen (CTLA4) which is a molecule that modifies T cell activation and with an adjuvant activity interfering with the adaptive immune response. The resulting plasmid, named pCMV-CTLA4-Ig-NG34, was administered twice to animals employing a needle-free delivery approach. Two studies were carried out to test the efficacy of pCMV-CTLA4-Ig-NG34 as a potential swine influenza vaccine, one in seronegative and another in seropositive pigs against SIV. The second one was aimed to evaluate whether pCMV-CTLA4-Ig-NG34 vaccination would overcome maternally derived antibodies (MDA). After immunization, all animals were intranasally challenged with an H3N2 influenza strain. A complete elimination or significant reduction in the viral shedding was observed within the first week after the challenge in the vaccinated animals from both studies. In addition, no challenged heterologous virus load was detected in the airways of vaccinated pigs. Overall, it is suggested that the pCMV-CTLA4-Ig-NG34 vaccine formulation could potentially be used as a multivalent vaccine against influenza viruses. © 2019 Sisteré-Oró et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
journal = "PLOS One",
title = "Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge",
volume = "14",
number = "3",
pages = "e0212431",
doi = "10.1371/journal.pone.0212431"
}

Sistere-Oro, M., Vergara-Alert, J., Stratmann, T., Lopez-Serrano, S., Pina-Pedrero, S., Cordoba, L., Perez-Maillo, M., Pleguezuelos, P., Vidal, E., Veljković, V., Segalés, J., Nielsen, J. P., Fomsgaard, A., Darji, A.,& Huber, V. C.. (2019). Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge. in PLOS One, 14(3), e0212431.
https://doi.org/10.1371/journal.pone.0212431

Sistere-Oro M, Vergara-Alert J, Stratmann T, Lopez-Serrano S, Pina-Pedrero S, Cordoba L, Perez-Maillo M, Pleguezuelos P, Vidal E, Veljković V, Segalés J, Nielsen JP, Fomsgaard A, Darji A, Huber VC. Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge. in PLOS One. 2019;14(3):e0212431.
doi:10.1371/journal.pone.0212431 .

Sistere-Oro, Marta, Vergara-Alert, Julia, Stratmann, Thomas, Lopez-Serrano, Sergi, Pina-Pedrero, Sonia, Cordoba, Lorena, Perez-Maillo, Monica, Pleguezuelos, Patricia, Vidal, Enric, Veljković, Veljko, Segalés, Joaquim, Nielsen, Jens Peter, Fomsgaard, Anders, Darji, Ayub, Huber, Victor C., "Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge" in PLOS One, 14, no. 3 (2019):e0212431,
https://doi.org/10.1371/journal.pone.0212431 . .

TY  - 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 . .