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To date, no evidence supports the fact that animals play a role in the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19). However, several animal species are naturally susceptible to SARS-CoV-2 infection. Besides pets (cats, dogs, Syrian hamsters, and ferrets) and farm animals (minks), different zoo animal species have tested positive for SARS-CoV-2 (large felids and non-human primates). After the summer of 2020, a second wave of SARS-CoV-2 infection occurred in Barcelona (Spain), reaching a peak of positive cases in November. During that period, four lions (Panthera leo) at the Barcelona Zoo and three caretakers developed respiratory signs and tested positive for the SARS-CoV-2 antigen. Lion infection was monitored for several weeks and nasal, fecal, saliva, and blood samples were taken at different time-points. SARS-CoV-2 RNA was detected in nasal samples from all studied lions and the viral RNA was detected up to two weeks after the initial viral positive test in three out of four animals. The SARS-CoV-2 genome was also detected in the feces of animals at different times. Virus isolation was successful only from respiratory samples of two lions at an early time-point. The four animals developed neutralizing antibodies after the infection that were detectable four months after the initial diagnosis. The partial SARS-CoV-2 genome sequence from one animal caretaker was identical to the sequences obtained from lions. Chronology of the events, the viral dynamics, and the genomic data support human-to-lion transmission as the origin of infection.
Hugo Fernández-Bellon; Jordi Rodon; Leira Fernández-Bastit; Vanessa Almagro; Pilar Padilla-Solé; Cristina Lorca-Oró; Rosa Valle; Núria Roca; Santina Grazioli; Tiziana Trogu; Albert Bensaid; Jorge Carrillo; Nuria Izquierdo-Useros; Julià Blanco; Mariona Parera; Marc Noguera-Julián; Bonaventura Clotet; Ana Moreno; Joaquim Segalés; Júlia Vergara-Alert. Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses. Viruses 2021, 13, 1683 .
AMA StyleHugo Fernández-Bellon, Jordi Rodon, Leira Fernández-Bastit, Vanessa Almagro, Pilar Padilla-Solé, Cristina Lorca-Oró, Rosa Valle, Núria Roca, Santina Grazioli, Tiziana Trogu, Albert Bensaid, Jorge Carrillo, Nuria Izquierdo-Useros, Julià Blanco, Mariona Parera, Marc Noguera-Julián, Bonaventura Clotet, Ana Moreno, Joaquim Segalés, Júlia Vergara-Alert. Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses. Viruses. 2021; 13 (9):1683.
Chicago/Turabian StyleHugo Fernández-Bellon; Jordi Rodon; Leira Fernández-Bastit; Vanessa Almagro; Pilar Padilla-Solé; Cristina Lorca-Oró; Rosa Valle; Núria Roca; Santina Grazioli; Tiziana Trogu; Albert Bensaid; Jorge Carrillo; Nuria Izquierdo-Useros; Julià Blanco; Mariona Parera; Marc Noguera-Julián; Bonaventura Clotet; Ana Moreno; Joaquim Segalés; Júlia Vergara-Alert. 2021. "Monitoring Natural SARS-CoV-2 Infection in Lions (Panthera leo) at the Barcelona Zoo: Viral Dynamics and Host Responses." Viruses 13, no. 9: 1683.
With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.1.7 variant. Our data show that parameters of natural infection (time from infection and nature of the infecting variant) determined cross-neutralization. Uninfected vaccinees showed a small reduction in neutralization against the B.1.1.7 variant compared to both the WH1 strain and the D614G mutant. Interestingly, upon vaccination, previously infected individuals developed more robust neutralizing responses against B.1.1.7, suggesting that vaccines can boost the neutralization breadth conferred by natural infection.
Benjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Ruth Toledo; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulàlia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals. Viruses 2021, 13, 1135 .
AMA StyleBenjamin Trinité, Edwards Pradenas, Silvia Marfil, Carla Rovirosa, Víctor Urrea, Ferran Tarrés-Freixas, Raquel Ortiz, Jordi Rodon, Júlia Vergara-Alert, Joaquim Segalés, Victor Guallar, Rosalba Lepore, Nuria Izquierdo-Useros, Glòria Trujillo, Jaume Trapé, Carolina González-Fernández, Antonia Flor, Rafel Pérez-Vidal, Ruth Toledo, Anna Chamorro, Roger Paredes, Ignacio Blanco, Eulàlia Grau, Marta Massanella, Jorge Carrillo, Bonaventura Clotet, Julià Blanco. Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals. Viruses. 2021; 13 (6):1135.
Chicago/Turabian StyleBenjamin Trinité; Edwards Pradenas; Silvia Marfil; Carla Rovirosa; Víctor Urrea; Ferran Tarrés-Freixas; Raquel Ortiz; Jordi Rodon; Júlia Vergara-Alert; Joaquim Segalés; Victor Guallar; Rosalba Lepore; Nuria Izquierdo-Useros; Glòria Trujillo; Jaume Trapé; Carolina González-Fernández; Antonia Flor; Rafel Pérez-Vidal; Ruth Toledo; Anna Chamorro; Roger Paredes; Ignacio Blanco; Eulàlia Grau; Marta Massanella; Jorge Carrillo; Bonaventura Clotet; Julià Blanco. 2021. "Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals." Viruses 13, no. 6: 1135.
While MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, while interferon stimulated genes (ISGs) were induced along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, seems central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.
Nigeer Te; Jordi Rodon; Maria Ballester; Mónica Pérez; Lola Pailler-García; Joaquim Segalés; Júlia Vergara-Alert; Albert Bensaid. Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are features of alpacas resolving MERS-CoV infection. PLOS Pathogens 2021, 17, e1009229 .
AMA StyleNigeer Te, Jordi Rodon, Maria Ballester, Mónica Pérez, Lola Pailler-García, Joaquim Segalés, Júlia Vergara-Alert, Albert Bensaid. Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are features of alpacas resolving MERS-CoV infection. PLOS Pathogens. 2021; 17 (5):e1009229.
Chicago/Turabian StyleNigeer Te; Jordi Rodon; Maria Ballester; Mónica Pérez; Lola Pailler-García; Joaquim Segalés; Júlia Vergara-Alert; Albert Bensaid. 2021. "Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are features of alpacas resolving MERS-CoV infection." PLOS Pathogens 17, no. 5: e1009229.
Reinfections with SARS-CoV-2 have already been documented in humans, although its real incidence is currently unknown. Besides having great impact on public health, this phenomenon raises the question if immunity generated by a single infection is sufficient to provide sterilizing/protective immunity to a subsequent SARS-CoV-2 re-exposure. The Golden Syrian hamster is a manageable animal model to explore immunological mechanisms able to counteract COVID-19, as it recapitulates pathological aspects of mild to moderately affected patients. Here, we report that SARS-CoV-2-inoculated hamsters resolve infection in the upper and lower respiratory tracts within seven days upon inoculation with the Cat01 (G614) SARS-CoV-2 isolate. Three weeks after primary challenge, and despite high titers of neutralizing antibodies, half of the animals were susceptible to reinfection by both identical (Cat01, G614) and variant (WA/1, D614) SARS-CoV-2 isolates. However, upon re-inoculation, only nasal tissues were transiently infected with much lower viral replication than those observed after the first inoculation. These data indicate that a primary SARS-CoV-2 infection is not sufficient to elicit a sterilizing immunity in hamster models but protects against lung disease.
Marco Brustolin; Jordi Rodon; María Luisa Rodríguez de la Concepción; Carlos Ávila-Nieto; Guillermo Cantero; Mónica Pérez; Nigeer Te; Marc Noguera-Julián; Víctor Guallar; Alfonso Valencia; Núria Roca; Nuria Izquierdo-Useros; Julià Blanco; Bonaventura Clotet; Albert Bensaid; Jorge Carrillo; Júlia Vergara-Alert; Joaquim Segalés. Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in golden Syrian hamster. Emerging Microbes & Infections 2021, 10, 797 -809.
AMA StyleMarco Brustolin, Jordi Rodon, María Luisa Rodríguez de la Concepción, Carlos Ávila-Nieto, Guillermo Cantero, Mónica Pérez, Nigeer Te, Marc Noguera-Julián, Víctor Guallar, Alfonso Valencia, Núria Roca, Nuria Izquierdo-Useros, Julià Blanco, Bonaventura Clotet, Albert Bensaid, Jorge Carrillo, Júlia Vergara-Alert, Joaquim Segalés. Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in golden Syrian hamster. Emerging Microbes & Infections. 2021; 10 (1):797-809.
Chicago/Turabian StyleMarco Brustolin; Jordi Rodon; María Luisa Rodríguez de la Concepción; Carlos Ávila-Nieto; Guillermo Cantero; Mónica Pérez; Nigeer Te; Marc Noguera-Julián; Víctor Guallar; Alfonso Valencia; Núria Roca; Nuria Izquierdo-Useros; Julià Blanco; Bonaventura Clotet; Albert Bensaid; Jorge Carrillo; Júlia Vergara-Alert; Joaquim Segalés. 2021. "Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in golden Syrian hamster." Emerging Microbes & Infections 10, no. 1: 797-809.
While MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, provoking the induction of interferon stimulated genes (ISGs) along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, is central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.Author summaryMiddle East respiratory syndrome coronavirus (MERS-CoV) is the etiological agent of a respiratory disease causing high mortality in humans. In camelids, the main MERS-CoV reservoir host, viral infection leads to subclinical disease. Our study describes transcriptional regulations of innate immunological pathways underlying asymptomatic clinical manifestations of alpacas in response to MERS-CoV. Concomitant to the peak of infection, these animals elicited a strong transient interferon response and induction of the anti-inflammatory cytokine IL10 in the nasal mucosa. This was associated to a dimmed regulation of pro-inflammatory cytokines and induction of interferon stimulated genes along the whole respiratory mucosa, leading to the rapid clearance of the virus. Thus, innate immune responses occurring in the nasal mucosa appear to be the key in controlling MERS-CoV disease by avoiding a cytokine storm. Understanding on how asymptomatic host reservoirs counteract MERS-CoV infection will aid in the development of antiviral drugs and vaccines.
Nigeer Te; Jordi Rodon; Maria Ballester; Mónica Pérez; Lola Pailler-García; Joaquim Segalés; Júlia Vergara-Alert; Albert Bensaid. Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection. 2020, 1 .
AMA StyleNigeer Te, Jordi Rodon, Maria Ballester, Mónica Pérez, Lola Pailler-García, Joaquim Segalés, Júlia Vergara-Alert, Albert Bensaid. Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection. . 2020; ():1.
Chicago/Turabian StyleNigeer Te; Jordi Rodon; Maria Ballester; Mónica Pérez; Lola Pailler-García; Joaquim Segalés; Júlia Vergara-Alert; Albert Bensaid. 2020. "Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection." , no. : 1.
While MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, provoking the induction of interferon stimulated genes (ISGs) along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, is central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.IMPORTANCEMiddle East respiratory syndrome coronavirus (MERS-CoV) is the etiological agent of a respiratory disease causing high mortality in humans. In camelids, the main MERS-CoV reservoir host, viral infection leads to subclinical disease. Our study describes transcriptional regulations of innate immunological pathways underlying asymptomatic clinical manifestations of alpacas in response to MERS-CoV. Concomitant to the peak of infection, these animals elicited a strong transient interferon response and induction of the anti-inflammatory cytokine IL10 in the nasal mucosa. This was associated to a dimmed regulation of pro-inflammatory cytokines and induction of interferon stimulated genes along the whole respiratory mucosa, leading to the rapid clearance of the virus. Thus, innate immune responses occurring in the nasal mucosa appear to be the key in controlling MERS-CoV disease by avoiding a cytokine storm. Understanding on how asymptomatic host reservoirs counteract MERS-CoV infection will aid in the development of antiviral drugs and vaccines.
Nigeer Te; Jordi Rodon; Maria Ballester; Mónica Pérez; Lola Pailler-García; Joaquim Segalés; Júlia Vergara-Alert; Albert Bensaid. Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection. 2020, 1 .
AMA StyleNigeer Te, Jordi Rodon, Maria Ballester, Mónica Pérez, Lola Pailler-García, Joaquim Segalés, Júlia Vergara-Alert, Albert Bensaid. Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection. . 2020; ():1.
Chicago/Turabian StyleNigeer Te; Jordi Rodon; Maria Ballester; Mónica Pérez; Lola Pailler-García; Joaquim Segalés; Júlia Vergara-Alert; Albert Bensaid. 2020. "Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection." , no. : 1.
Conventional piglets were inoculated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) through different routes, including intranasal, intratracheal, intramuscular and intravenous ones. Although piglets were not susceptible to SARS‐CoV‐2 and lacked lesions or viral RNA in tissues/swabs, seroconversion was observed in pigs inoculated parenterally (intramuscularly or intravenously).
Júlia Vergara‐Alert; Jordi Rodon; Jorge Carrillo; Nigeer Te; Nuria Izquierdo‐Useros; María Luisa Rodríguez de la Concepción; Carlos Ávila‐Nieto; Víctor Guallar; Alfonso Valencia; Guillermo Cantero; Julià Blanco; Bonaventura Clotet; Albert Bensaid; Joaquim Segalés. Pigs are not susceptible to SARS‐CoV‐2 infection but are a model for viral immunogenicity studies. Transboundary and Emerging Diseases 2020, 1 .
AMA StyleJúlia Vergara‐Alert, Jordi Rodon, Jorge Carrillo, Nigeer Te, Nuria Izquierdo‐Useros, María Luisa Rodríguez de la Concepción, Carlos Ávila‐Nieto, Víctor Guallar, Alfonso Valencia, Guillermo Cantero, Julià Blanco, Bonaventura Clotet, Albert Bensaid, Joaquim Segalés. Pigs are not susceptible to SARS‐CoV‐2 infection but are a model for viral immunogenicity studies. Transboundary and Emerging Diseases. 2020; ():1.
Chicago/Turabian StyleJúlia Vergara‐Alert; Jordi Rodon; Jorge Carrillo; Nigeer Te; Nuria Izquierdo‐Useros; María Luisa Rodríguez de la Concepción; Carlos Ávila‐Nieto; Víctor Guallar; Alfonso Valencia; Guillermo Cantero; Julià Blanco; Bonaventura Clotet; Albert Bensaid; Joaquim Segalés. 2020. "Pigs are not susceptible to SARS‐CoV‐2 infection but are a model for viral immunogenicity studies." Transboundary and Emerging Diseases , no. : 1.
Background There is a crucial need for effective therapies that are immediately available to counteract COVID-19 disease. Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. In this study, the same products were tested for neutralization activity against SARS-CoV-2, SARS-CoV and MERS-CoV and their potential as an antiviral therapy. Methods The neutralization capacity of six selected lots of IVIG was assessed against SARS-CoV-2 (two different isolates), SARS-CoV and MERS-CoV in cell cultures. Infectivity neutralization was measured by determining the percent reduction in plaque-forming units (PFU) and by cytopathic effects for two IVIG lots in one of the SARS-CoV-2 isolates. Neutralization was quantified using the plaque reduction neutralization test 50 (PRNT50) in the PFU assay and the half maximal inhibitory concentration (IC50) in the cytopathic/cytotoxic method (calculated as the minus log10 dilution which reduced the viral titer by 50%). Results All IVIG preparations showed neutralization of both SARS-CoV-2 isolates, ranging from 79 to 89.5% with PRNT50 titers from 4.5 to >5 for the PFU method and ranging from 47.0%-64.7% with an IC50 ~1 for the cytopathic method. All IVIG lots produced neutralization of SARS-CoV ranging from 39.5 to 55.1 % and PRNT50 values ranging from 2.0 to 3.3. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. However, no neutralization capacity was demonstrated against MERS-CoV. These preparations are currently available and may be immediately useful for COVID-19 management.
José-María Díez; Carolina Romero; Júlia Vergara-Alert; Melissa Belló-Perez; Jordi Rodon; José Manuel Honrubia; Joaquim Segalés; Isabel Sola; Luis Enjuanes; Rodrigo Gajardo. Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins. 2020, 1 .
AMA StyleJosé-María Díez, Carolina Romero, Júlia Vergara-Alert, Melissa Belló-Perez, Jordi Rodon, José Manuel Honrubia, Joaquim Segalés, Isabel Sola, Luis Enjuanes, Rodrigo Gajardo. Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins. . 2020; ():1.
Chicago/Turabian StyleJosé-María Díez; Carolina Romero; Júlia Vergara-Alert; Melissa Belló-Perez; Jordi Rodon; José Manuel Honrubia; Joaquim Segalés; Isabel Sola; Luis Enjuanes; Rodrigo Gajardo. 2020. "Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins." , no. : 1.
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.
Marta Sisteré-Oró; Júlia Vergara-Alert; Thomas Stratmann; Sergi López-Serrano; Sonia Pina-Pedrero; Lorena Córdoba; Mónica Pérez-Maillo; Patrícia Pleguezuelos; Enric Vidal; Veljko Veljkovic; Joaquim Segalés; Jens Nielsen; Anders Fomsgaard; Ayub Darji. Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge. PLOS ONE 2019, 14, e0212431 .
AMA StyleMarta Sisteré-Oró, Júlia Vergara-Alert, Thomas Stratmann, Sergi López-Serrano, Sonia Pina-Pedrero, Lorena Córdoba, Mónica Pérez-Maillo, Patrícia Pleguezuelos, Enric Vidal, Veljko Veljkovic, Joaquim Segalés, Jens Nielsen, Anders Fomsgaard, Ayub Darji. Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge. PLOS ONE. 2019; 14 (3):e0212431.
Chicago/Turabian StyleMarta Sisteré-Oró; Júlia Vergara-Alert; Thomas Stratmann; Sergi López-Serrano; Sonia Pina-Pedrero; Lorena Córdoba; Mónica Pérez-Maillo; Patrícia Pleguezuelos; Enric Vidal; Veljko Veljkovic; Joaquim Segalés; Jens Nielsen; Anders Fomsgaard; Ayub Darji. 2019. "Conserved HA-peptide NG34 formulated in pCMV-CTLA4-Ig reduces viral shedding in pigs after a heterosubtypic influenza virus SwH3N2 challenge." PLOS ONE 14, no. 3: e0212431.
The ongoing Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks pose a worldwide public health threat. Blocking MERS-CoV zoonotic transmission from dromedary camels, the animal reservoir, could potentially reduce the number of primary human cases. Here we report MERS-CoV transmission from experimentally infected llamas to naïve animals. Directly inoculated llamas shed virus for at least 6 days and could infect all in-contact naïve animals 4–5 days after exposure. With the aim to block virus transmission, we examined the efficacy of a recombinant spike S1-protein vaccine. In contrast to naïve animals, in-contact vaccinated llamas did not shed infectious virus upon exposure to directly inoculated llamas, consistent with the induction of strong virus neutralizing antibody responses. Our data provide further evidence that vaccination of the reservoir host may impede MERS-CoV zoonotic transmission to humans.
Jordi Rodon; Nisreen M. A. Okba; Nigeer Te; Brenda Van Dieren; Berend-Jan Bosch; Albert Bensaid; Joaquim Segalés; Bart L. Haagmans; Júlia Vergara-Alert. Blocking transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in llamas by vaccination with a recombinant spike protein. Emerging Microbes & Infections 2019, 8, 1593 -1603.
AMA StyleJordi Rodon, Nisreen M. A. Okba, Nigeer Te, Brenda Van Dieren, Berend-Jan Bosch, Albert Bensaid, Joaquim Segalés, Bart L. Haagmans, Júlia Vergara-Alert. Blocking transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in llamas by vaccination with a recombinant spike protein. Emerging Microbes & Infections. 2019; 8 (1):1593-1603.
Chicago/Turabian StyleJordi Rodon; Nisreen M. A. Okba; Nigeer Te; Brenda Van Dieren; Berend-Jan Bosch; Albert Bensaid; Joaquim Segalés; Bart L. Haagmans; Júlia Vergara-Alert. 2019. "Blocking transmission of Middle East respiratory syndrome coronavirus (MERS-CoV) in llamas by vaccination with a recombinant spike protein." Emerging Microbes & Infections 8, no. 1: 1593-1603.
This study investigated the co‐localization of the Middle East respiratory syndrome coronavirus (MERS‐CoV) and its receptor dipeptidyl peptidase‐4 (DPP4) by immunohistochemistry (IHC) across respiratory and lymphoid organs of experimentally MERS‐CoV infected pigs and llamas. Also, scanning electron microscopy was performed to assess the ciliary integrity of respiratory epithelial cells in both species. In pigs, on day 2 post‐inoculation (p.i.), DPP4‐MERS‐CoV co‐localization was detected in medial turbinate epithelium. On day 4 p.i., the virus/receptor co‐localized in frontal and medial turbinate epithelial cells in pigs, and epithelial cells distributed unevenly through the whole nasal cavity and in the cervical lymph node in llamas. MERS‐CoV viral nucleocapsid was mainly detected in upper respiratory tract sites on days 2 and 4 p.i. in pigs and day 4 p.i. in llamas. No MERS‐CoV was detected on day 24 p.i. in any tissue by IHC. While pigs showed severe ciliary loss in the nasal mucosa both on days 2 and 4 p.i. and moderate loss in the trachea on days 4 and 24 p.i., ciliation of respiratory organs in llamas was not significantly affected. Obtained data confirm the role of DPP4 for MERS‐CoV entry in respiratory epithelial cells of llamas. Notably, several nasal epithelial cells in pigs were found to express viral antigen but not DPP4, suggesting the possible existence of other molecule/s facilitating virus entry or down regulation of DPP4 upon infection.
Nigeer Te; Júlia Vergara-Alert; Annika Lehmbecker; Mónica Pérez; Bart L. Haagmans; Wolfgang Baumgärtner; Albert Bensaid; Joaquim Segalés. Co‐localization of Middle East respiratory syndrome coronavirus (MERS‐CoV) and dipeptidyl peptidase‐4 in the respiratory tract and lymphoid tissues of pigs and llamas. Transboundary and Emerging Diseases 2018, 66, 831 -841.
AMA StyleNigeer Te, Júlia Vergara-Alert, Annika Lehmbecker, Mónica Pérez, Bart L. Haagmans, Wolfgang Baumgärtner, Albert Bensaid, Joaquim Segalés. Co‐localization of Middle East respiratory syndrome coronavirus (MERS‐CoV) and dipeptidyl peptidase‐4 in the respiratory tract and lymphoid tissues of pigs and llamas. Transboundary and Emerging Diseases. 2018; 66 (2):831-841.
Chicago/Turabian StyleNigeer Te; Júlia Vergara-Alert; Annika Lehmbecker; Mónica Pérez; Bart L. Haagmans; Wolfgang Baumgärtner; Albert Bensaid; Joaquim Segalés. 2018. "Co‐localization of Middle East respiratory syndrome coronavirus (MERS‐CoV) and dipeptidyl peptidase‐4 in the respiratory tract and lymphoid tissues of pigs and llamas." Transboundary and Emerging Diseases 66, no. 2: 831-841.
Middle East respiratory syndrome (MERS) represents an important respiratory disease accompanied by lethal outcome in one-third of human patients. Recent data indicate that dromedaries represent an important source of infection, although information regarding viral cell tropism and pathogenesis is sparse. In the current study, tissues of eight dromedaries receiving inoculation of MERS-Coronavirus (MERS-CoV) after recombinant Modified-Vaccinia-Virus-Ankara (MVA-S)-vaccination (n = 4), MVA-vaccination (mock vaccination, n = 2) and PBS application (mock vaccination, n = 2), respectively, were investigated. Tissues were analyzed by histology, immunohistochemistry, immunofluorescence, and scanning electron microscopy. MERS-CoV infection in mock-vaccinated dromedaries revealed high numbers of MERS-CoV-nucleocapsid positive cells, T cells, and macrophages within nasal turbinates and trachea at day four post infection. Double immunolabeling demonstrated cytokeratin (CK) 18 expressing epithelial cells to be the prevailing target cell of MERS-CoV, while CK5/6 and CK14 expressing cells did not co-localize with virus. In addition, virus was occasionally detected in macrophages. The acute disease was further accompanied by ciliary loss along with a lack of dipeptidyl peptidase 4 (DPP4), known to mediate virus entry. DPP4 was mainly expressed by human lymphocytes and dromedary monocytes, but overall the expression level was lower in dromedaries. The present study underlines significant species-specific manifestations of MERS and highlights ciliary loss as an important finding in dromedaries. The obtained results promote a better understanding of coronavirus infections, which pose major health challenges.
Ann-Kathrin Haverkamp; Annika Lehmbecker; Ingo Spitzbarth; Widagdo Widagdo; Bart L. Haagmans; Joaquim Segalés; Júlia Vergara-Alert; Albert Bensaid; Judith M. A. Van Den Brand; Albert D. M. E. Osterhaus; Wolfgang Baumgärtner. Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4. Scientific Reports 2018, 8, 1 -15.
AMA StyleAnn-Kathrin Haverkamp, Annika Lehmbecker, Ingo Spitzbarth, Widagdo Widagdo, Bart L. Haagmans, Joaquim Segalés, Júlia Vergara-Alert, Albert Bensaid, Judith M. A. Van Den Brand, Albert D. M. E. Osterhaus, Wolfgang Baumgärtner. Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4. Scientific Reports. 2018; 8 (1):1-15.
Chicago/Turabian StyleAnn-Kathrin Haverkamp; Annika Lehmbecker; Ingo Spitzbarth; Widagdo Widagdo; Bart L. Haagmans; Joaquim Segalés; Júlia Vergara-Alert; Albert Bensaid; Judith M. A. Van Den Brand; Albert D. M. E. Osterhaus; Wolfgang Baumgärtner. 2018. "Experimental infection of dromedaries with Middle East respiratory syndrome-Coronavirus is accompanied by massive ciliary loss and depletion of the cell surface receptor dipeptidyl peptidase 4." Scientific Reports 8, no. 1: 1-15.
Circulation of highly pathogenic avian influenza (HPAI) viruses poses a continuous threat to animal and public health. After the 2005–2006 H5N1 and the 2014–2015 H5N8 epidemics, another H5N8 is currently affecting Europe. Up to August 2017, 1,112 outbreaks in domestic and 955 in wild birds in 30 European countries have been reported, the largest epidemic by a HPAI virus in the continent. Here, the main epidemiological findings are described. While some similarities with previous HPAI virus epidemics were observed, for example in the pattern of emergence, significant differences were also patent, in particular the size and extent of the epidemic. Even though no human infections have been reported to date, the fact that A/H5N8 has affected so far 1,112 domestic holdings, increases the risk of exposure of humans and therefore represents a concern. Understanding the epidemiology of HPAI viruses is essential for the planning future surveillance and control activities.
S. Napp; N. Majó; R. Sánchez-Gónzalez; Júlia Vergara-Alert. Emergence and spread of highly pathogenic avian influenza A(H5N8) in Europe in 2016-2017. Transboundary and Emerging Diseases 2018, 65, 1217 -1226.
AMA StyleS. Napp, N. Majó, R. Sánchez-Gónzalez, Júlia Vergara-Alert. Emergence and spread of highly pathogenic avian influenza A(H5N8) in Europe in 2016-2017. Transboundary and Emerging Diseases. 2018; 65 (5):1217-1226.
Chicago/Turabian StyleS. Napp; N. Majó; R. Sánchez-Gónzalez; Júlia Vergara-Alert. 2018. "Emergence and spread of highly pathogenic avian influenza A(H5N8) in Europe in 2016-2017." Transboundary and Emerging Diseases 65, no. 5: 1217-1226.
Influenza A virus in swine herds represents a major problem for the swine industry and poses a constant threat for the emergence of novel pandemic viruses and the development of more effective influenza vaccines for pigs is desired. By optimizing the vector backbone and using a needle-free delivery method, we have recently demonstrated a polyvalent influenza DNA vaccine that induces a broad immune response, including both humoral and cellular immunity. To investigate the protection of our polyvalent influenza DNA vaccine approach in a pig challenge study. By intradermal needle-free delivery to the skin, we immunized pigs with two different doses (500 μg and 800 μg) of an influenza DNA vaccine based on six genes of pandemic origin, including internally expressed matrix and nucleoprotein and externally expressed hemagglutinin and neuraminidase as previously demonstrated. Two weeks following immunization, the pigs were challenged with the 2009 pandemic H1N1 virus. When challenged with 2009 pandemic H1N1, 0/5 vaccinated pigs (800 μg DNA) became infected whereas 5/5 unvaccinated control pigs were infected. The pigs vaccinated with the low dose (500 μg DNA) were only partially protected. The DNA vaccine elicited binding-, hemagglutination inhibitory (HI) − as well as cross-reactive neutralizing antibody activity and neuraminidase inhibiting antibodies in the immunized pigs, in a dose-dependent manner. The present data, together with the previously demonstrated immunogenicity of our influenza DNA vaccine, indicate that naked DNA vaccine technology provides a strong approach for the development of improved pig vaccines, applying realistic low doses of DNA and a convenient delivery method for mass vaccination.
Ingrid Karlsson; Marie Borggren; Maiken Worsøe Rosenstierne; Ramona Trebbien; James A. Williams; Enric Vidal; Júlia Vergara-Alert; David Solanes Foz; Ayub Darji; Marta Sisteré-Oró; Joaquim Segalés; Jens Nielsen; Anders Fomsgaard. Protective effect of a polyvalent influenza DNA vaccine in pigs. Veterinary Immunology and Immunopathology 2017, 195, 25 -32.
AMA StyleIngrid Karlsson, Marie Borggren, Maiken Worsøe Rosenstierne, Ramona Trebbien, James A. Williams, Enric Vidal, Júlia Vergara-Alert, David Solanes Foz, Ayub Darji, Marta Sisteré-Oró, Joaquim Segalés, Jens Nielsen, Anders Fomsgaard. Protective effect of a polyvalent influenza DNA vaccine in pigs. Veterinary Immunology and Immunopathology. 2017; 195 ():25-32.
Chicago/Turabian StyleIngrid Karlsson; Marie Borggren; Maiken Worsøe Rosenstierne; Ramona Trebbien; James A. Williams; Enric Vidal; Júlia Vergara-Alert; David Solanes Foz; Ayub Darji; Marta Sisteré-Oró; Joaquim Segalés; Jens Nielsen; Anders Fomsgaard. 2017. "Protective effect of a polyvalent influenza DNA vaccine in pigs." Veterinary Immunology and Immunopathology 195, no. : 25-32.
Dromedary camels are the main reservoir of Middle East respiratory syndrome coronavirus (MERS‐CoV), but other livestock species (i.e., alpacas, llamas, and pigs) are also susceptible to infection with MERS‐CoV. Animal‐to‐animal transmission in alpacas was reported, but evidence for transmission in other species has not been proved. This study explored pig‐to‐pig MERS‐CoV transmission experimentally. Virus was present in nasal swabs of infected animals, and limited amounts of viral RNA, but no infectious virus were detected in the direct contact pigs. No virus was detected in the indirect contact group. Furthermore, direct and indirect contact pigs did not develop specific antibodies against MERS‐CoV. Therefore, the role of pigs as reservoir is probably negligible, although it deserves further confirmation.
J. Vergara-Alert; Victor Stalin Raj; M. Muñoz; F. X. Abad; I. Cordón; B. L. Haagmans; Albert Bensaid; J. Segalés. Middle East respiratory syndrome coronavirus experimental transmission using a pig model. Transboundary and Emerging Diseases 2017, 64, 1342 -1345.
AMA StyleJ. Vergara-Alert, Victor Stalin Raj, M. Muñoz, F. X. Abad, I. Cordón, B. L. Haagmans, Albert Bensaid, J. Segalés. Middle East respiratory syndrome coronavirus experimental transmission using a pig model. Transboundary and Emerging Diseases. 2017; 64 (5):1342-1345.
Chicago/Turabian StyleJ. Vergara-Alert; Victor Stalin Raj; M. Muñoz; F. X. Abad; I. Cordón; B. L. Haagmans; Albert Bensaid; J. Segalés. 2017. "Middle East respiratory syndrome coronavirus experimental transmission using a pig model." Transboundary and Emerging Diseases 64, no. 5: 1342-1345.
Hugo Fernández Bellon; Júlia Vergara-Alert; V. Almagro; R. Rivas; N. Majó; N. Busquets; A. Ramis. Evidence that avian influenza vaccination induces long-lived immune responses in zoo birds. Veterinary Record 2017, 180, 544 -544.
AMA StyleHugo Fernández Bellon, Júlia Vergara-Alert, V. Almagro, R. Rivas, N. Majó, N. Busquets, A. Ramis. Evidence that avian influenza vaccination induces long-lived immune responses in zoo birds. Veterinary Record. 2017; 180 (22):544-544.
Chicago/Turabian StyleHugo Fernández Bellon; Júlia Vergara-Alert; V. Almagro; R. Rivas; N. Majó; N. Busquets; A. Ramis. 2017. "Evidence that avian influenza vaccination induces long-lived immune responses in zoo birds." Veterinary Record 180, no. 22: 544-544.
Emerging and re-emerging pathogens represent a substantial threat to public health, as demonstrated with numerous outbreaks over the past years, including the 2013–2016 outbreak of Ebola virus in western Africa. Coronaviruses are also a threat for humans, as evidenced in 2002/2003 with infection by the severe acute respiratory syndrome coronavirus (SARS-CoV), which caused more than 8000 human infections with 10% fatality rate in 37 countries. Ten years later, a novel human coronavirus (Middle East respiratory syndrome coronavirus, MERS-CoV), associated with severe pneumonia, arose in the Kingdom of Saudi Arabia. Until December 2016, MERS has accounted for more than 1800 cases and 35% fatality rate. Finding an animal model of disease is key to develop vaccines or antivirals against such emerging pathogens and to understand its pathogenesis. Knowledge of the potential role of domestic livestock and other animal species in the transmission of pathogens is of importance to understand the epidemiology of the disease. Little is known about MERS-CoV animal host range. In this paper, experimental data on potential hosts for MERS-CoV is reviewed. Advantages and limitations of different animal models are evaluated in relation to viral pathogenesis and transmission studies. Finally, the relevance of potential new target species is discussed.
Júlia Vergara-Alert; Enric Vidal; Albert Bensaid; Joaquim Segalés. Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS) coronavirus. One Health 2017, 3, 34 -40.
AMA StyleJúlia Vergara-Alert, Enric Vidal, Albert Bensaid, Joaquim Segalés. Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS) coronavirus. One Health. 2017; 3 ():34-40.
Chicago/Turabian StyleJúlia Vergara-Alert; Enric Vidal; Albert Bensaid; Joaquim Segalés. 2017. "Searching for animal models and potential target species for emerging pathogens: Experience gained from Middle East respiratory syndrome (MERS) coronavirus." One Health 3, no. : 34-40.
Middle East respiratory syndrome (MERS) cases continue to be reported, predominantly in Saudi Arabia and occasionally other countries. Although dromedaries are the main reservoir, other animal species might be susceptible to MERS coronavirus (MERS-CoV) infection and potentially serve as reservoirs. To determine whether other animals are potential reservoirs, we inoculated MERS-CoV into llamas, pigs, sheep, and horses and collected nasal and rectal swab samples at various times. The presence of MERS-CoV in the nose of pigs and llamas was confirmed by PCR, titration of infectious virus, immunohistochemistry, and in situ hybridization; seroconversion was detected in animals of both species. Conversely, in sheep and horses, virus-specific antibodies did not develop and no evidence of viral replication in the upper respiratory tract was found. These results prove the susceptibility of llamas and pigs to MERS-CoV infection. Thus, the possibility of MERS-CoV circulation in animals other than dromedaries, such as llamas and pigs, is not negligible.
Júlia Vergara-Alert; Judith M.A. Van Den Brand; W. Widagdo; Marta Muñoz; Victor Stalin Raj; Debby Schipper; David Solanes; Ivan Cordón; Albert Bensaid; Bart L. Haagmans; Joaquim Segalés. Livestock Susceptibility to Infection with Middle East Respiratory Syndrome Coronavirus. Emerging Infectious Diseases 2017, 23, 232 -240.
AMA StyleJúlia Vergara-Alert, Judith M.A. Van Den Brand, W. Widagdo, Marta Muñoz, Victor Stalin Raj, Debby Schipper, David Solanes, Ivan Cordón, Albert Bensaid, Bart L. Haagmans, Joaquim Segalés. Livestock Susceptibility to Infection with Middle East Respiratory Syndrome Coronavirus. Emerging Infectious Diseases. 2017; 23 (2):232-240.
Chicago/Turabian StyleJúlia Vergara-Alert; Judith M.A. Van Den Brand; W. Widagdo; Marta Muñoz; Victor Stalin Raj; Debby Schipper; David Solanes; Ivan Cordón; Albert Bensaid; Bart L. Haagmans; Joaquim Segalés. 2017. "Livestock Susceptibility to Infection with Middle East Respiratory Syndrome Coronavirus." Emerging Infectious Diseases 23, no. 2: 232-240.
Avian influenza (AI) can represent a threat to endangered wild birds, as demonstrated with the H5N1 highly pathogenic AI (HPAI) outbreaks. Vaccination against AI using inactivated H5-vaccines has been shown to induce humoral immune response in zoo bird species. In this study, the long-term efficacy of H5-vaccination was evaluated in flamingoes from Barcelona Zoo. Specific H5-antibody titres were maintained at high levels (geometric mean titres ≥32) for over 7 years after vaccination, both against the H5N9 and H5N3 vaccine strains, as well as H5N3 and H5N1 reference strains. In addition the breadth of the immune response was also studied by testing antibody production against H1-, H3-, H4-, H7-, and H10-subtypes. It was observed that most flamingoes presented specific antibodies against H1 virus subtypes, but titres to the other HA-subtypes were rarely detected. We show that AI-vaccines can induce immunity lasting seven years in flamingoes, which suggests that vaccination can provide long term protection from HPAI outbreaks in zoo birds.
Hugo Fernández Bellon; Júlia Vergara-Alert; Vanessa Almagro; Raquel Rivas; Azucena Sánchez; María Carmen Martínez; Natàlia Majó; Núria Busquets; Antonio Ramis. Vaccination against H5 avian influenza virus induces long-term humoral immune responses in flamingoes ( Phoenicopterus spp.). Vaccine 2016, 34, 3082 -3086.
AMA StyleHugo Fernández Bellon, Júlia Vergara-Alert, Vanessa Almagro, Raquel Rivas, Azucena Sánchez, María Carmen Martínez, Natàlia Majó, Núria Busquets, Antonio Ramis. Vaccination against H5 avian influenza virus induces long-term humoral immune responses in flamingoes ( Phoenicopterus spp.). Vaccine. 2016; 34 (27):3082-3086.
Chicago/Turabian StyleHugo Fernández Bellon; Júlia Vergara-Alert; Vanessa Almagro; Raquel Rivas; Azucena Sánchez; María Carmen Martínez; Natàlia Majó; Núria Busquets; Antonio Ramis. 2016. "Vaccination against H5 avian influenza virus induces long-term humoral immune responses in flamingoes ( Phoenicopterus spp.)." Vaccine 34, no. 27: 3082-3086.
In 2012, the first cases of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) were identified. Since then, more than 1,000 cases of MERS-CoV infection have been confirmed; infection is typically associated with considerable morbidity and, in approximately 30% of cases, mortality. Currently, there is no protective vaccine available. Replication-competent recombinant measles virus (MV) expressing foreign antigens constitutes a promising tool to induce protective immunity against corresponding pathogens. Therefore, we generated MVs expressing the spike glycoprotein of MERS-CoV in its full-length (MERS-S) or a truncated, soluble variant of MERS-S (MERS-solS). The genes encoding MERS-S and MERS-solS were cloned into the vaccine strain MV vac2 genome, and the respective viruses were rescued (MV vac2 -CoV-S and MV vac2 -CoV-solS). These recombinant MVs were amplified and characterized at passages 3 and 10. The replication of MV vac2 -CoV-S in Vero cells turned out to be comparable to that of the control virus MV vac2 -GFP (encoding green fluorescent protein), while titers of MV vac2 -CoV-solS were impaired approximately 3-fold. The genomic stability and expression of the inserted antigens were confirmed via sequencing of viral cDNA and immunoblot analysis. In vivo , immunization of type I interferon receptor-deficient (IFNAR −/− )-CD46Ge mice with 2 × 10 5 50% tissue culture infective doses of MV vac2 -CoV-S(H) or MV vac2 -CoV-solS(H) in a prime-boost regimen induced robust levels of both MV- and MERS-CoV-neutralizing antibodies. Additionally, induction of specific T cells was demonstrated by T cell proliferation, antigen-specific T cell cytotoxicity, and gamma interferon secretion after stimulation of splenocytes with MERS-CoV-S presented by murine dendritic cells. MERS-CoV challenge experiments indicated the protective capacity of these immune responses in vaccinated mice. IMPORTANCE Although MERS-CoV has not yet acquired extensive distribution, being mainly confined to the Arabic and Korean peninsulas, it could adapt to spread more readily among humans and thereby become pandemic. Therefore, the development of a vaccine is mandatory. The integration of antigen-coding genes into recombinant MV resulting in coexpression of MV and foreign antigens can efficiently be achieved. Thus, in combination with the excellent safety profile of the MV vaccine, recombinant MV seems to constitute an ideal vaccine platform. The present study shows that a recombinant MV expressing MERS-S is genetically stable and induces strong humoral and cellular immunity against MERS-CoV in vaccinated mice. Subsequent challenge experiments indicated protection of vaccinated animals, illustrating the potential of MV as a vaccine platform with the potential to target emerging infections, such as MERS-CoV.
Anna H. Malczyk; Alexandra Kupke; Steffen Prüfer; Vivian A. Scheuplein; Stefan Hutzler; Dorothea Kreuz; Tim Beissert; Stefanie Bauer; Stefanie Hubich-Rau; Christiane Tondera; Hosam Shams Eldin; Jörg Schmidt; Júlia Vergara-Alert; Yasemin Süzer; Janna Seifried; Kay-Martin Hanschmann; Ulrich Kalinke; Susanne Herold; Ugur Sahin; Klaus Cichutek; Zoe Waibler; Markus Eickmann; Stephan Becker; Michael D. Mühlebach. A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform. Journal of Virology 2015, 89, 11654 -11667.
AMA StyleAnna H. Malczyk, Alexandra Kupke, Steffen Prüfer, Vivian A. Scheuplein, Stefan Hutzler, Dorothea Kreuz, Tim Beissert, Stefanie Bauer, Stefanie Hubich-Rau, Christiane Tondera, Hosam Shams Eldin, Jörg Schmidt, Júlia Vergara-Alert, Yasemin Süzer, Janna Seifried, Kay-Martin Hanschmann, Ulrich Kalinke, Susanne Herold, Ugur Sahin, Klaus Cichutek, Zoe Waibler, Markus Eickmann, Stephan Becker, Michael D. Mühlebach. A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform. Journal of Virology. 2015; 89 (22):11654-11667.
Chicago/Turabian StyleAnna H. Malczyk; Alexandra Kupke; Steffen Prüfer; Vivian A. Scheuplein; Stefan Hutzler; Dorothea Kreuz; Tim Beissert; Stefanie Bauer; Stefanie Hubich-Rau; Christiane Tondera; Hosam Shams Eldin; Jörg Schmidt; Júlia Vergara-Alert; Yasemin Süzer; Janna Seifried; Kay-Martin Hanschmann; Ulrich Kalinke; Susanne Herold; Ugur Sahin; Klaus Cichutek; Zoe Waibler; Markus Eickmann; Stephan Becker; Michael D. Mühlebach. 2015. "A Highly Immunogenic and Protective Middle East Respiratory Syndrome Coronavirus Vaccine Based on a Recombinant Measles Virus Vaccine Platform." Journal of Virology 89, no. 22: 11654-11667.