scholarly journals Evaluation of the Pathogenicity and the Escape from Vaccine Protection of a New Antigenic Variant Derived from the European Human-Like Reassortant Swine H1N2 Influenza Virus

Viruses ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 1155 ◽  
Author(s):  
Céline Deblanc ◽  
Stéphane Quéguiner ◽  
Stéphane Gorin ◽  
Amélie Chastagner ◽  
Séverine Hervé ◽  
...  
Keyword(s):  
Influenza A ◽  
Inflammatory Responses ◽  
Clinical Signs ◽  
Parental Virus ◽  
Influenza A Viruses ◽  
Antigenic Variant ◽  
Vaccine Protection ◽  
Live Virus ◽  
Virus Shedding ◽  
Variant Strain

The surveillance of swine influenza A viruses in France revealed the emergence of an antigenic variant following deletions and mutations that are fixed in the HA-encoding gene of the European human-like reassortant swine H1N2 lineage. In this study, we compared the outcomes of the parental (H1huN2) and variant (H1huN2Δ14–147) virus infections in experimentally-inoculated piglets. Moreover, we assessed and compared the protection that was conferred by an inactivated vaccine currently licensed in Europe. Three groups of five unvaccinated or vaccinated piglets were inoculated with H1huN2 or H1huN2Δ14–147 or mock-inoculated, respectively. In unvaccinated piglets, the variant strain induced greater clinical signs than the parental virus, in relation to a higher inflammatory response that involves TNF-α production and a huge afflux of granulocytes into the lung. However, both infections led to similar levels of virus excretion and adaptive (humoral and cellular) immune responses in blood. The vaccinated animals were clinically protected from both infectious challenges and did not exhibit any inflammatory responses, regardless the inoculated virus. However, whereas vaccination prevented virus shedding in H1huN2-infected animals, it did not completely inhibit the multiplication of the variant strain, since live virus particles were detected in nasal secretions that were taken from H1huN2Δ14–147-inoculated vaccinated piglets. This difference in the level of vaccine protection was probably related to the poorer ability of the post-vaccine antibodies to neutralize the variant virus than the parental virus, even though post-vaccine cellular immunity appeared to be equally effective against both viruses. These results suggest that vaccine antigens would potentially need to be updated if this variant becomes established in Europe.

scholarly journals Immunization of pigs with an attenuated pseudorabies virus recombinant expressing the haemagglutinin of pandemic swine origin H1N1 influenza A virus

2014 ◽  
Vol 95 (4) ◽  
pp. 948-959 ◽  
Author(s):  
Katharina Klingbeil ◽  
Elke Lange ◽  
Jens P. Teifke ◽  
Thomas C. Mettenleiter ◽  
Walter Fuchs
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Pseudorabies Virus ◽  
Clinical Signs ◽  
H1n1 Influenza ◽  
Murine Cytomegalovirus ◽  
Human Pathogens ◽  
Live Virus ◽  
Challenge Virus ◽  
Virus Shedding

Pigs can be severely harmed by influenza, and represent important reservoir hosts, in which new human pathogens such as the recent pandemic swine-origin H1N1 influenza A virus can arise by mutation and reassortment of genome segments. To obtain novel, safe influenza vaccines for pigs, and to investigate the antigen-specific immune response, we modified an established live-virus vaccine against Aujeszky’s disease of swine, pseudorabies virus (PrV) strain Bartha (PrV-Ba), to serve as vector for the expression of haemagglutinin (HA) of swine-origin H1N1 virus. To facilitate transgene insertion, the genome of PrV-Ba was cloned as a bacterial artificial chromosome. HA expression occurred under control of the human or murine cytomegalovirus immediate early promoters (P-HCMV, P-MCMV), but could be substantially enhanced by synthetic introns and adaptation of the codon usage to that of PrV. However, despite abundant expression, the heterologous glycoprotein was not detectably incorporated into mature PrV particles. Replication of HA-expressing PrV in cell culture was only slightly affected compared to that of the parental virus strain. A single immunization of pigs with the PrV vector expressing the codon-optimized HA gene under control of P-MCMV induced high levels of HA-specific antibodies. The vaccinated animals were protected from clinical signs after challenge with a related swine-origin H1N1 influenza A virus, and challenge virus shedding was significantly reduced.

scholarly journals A Brazilian glycoprotein E-negative bovine herpesvirus type 1.2a (BHV-1.2a) mutant is attenuated for cattle and induces protection against wild-type virus challenge

2002 ◽  
Vol 22 (4) ◽  
pp. 135-140 ◽  
Author(s):  
Ana Cláudia Franco ◽  
Fernando Rosado Spilki ◽  
Paulo Augusto Esteves ◽  
Marcelo de Lima ◽  
Rudi Weiblen ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Bovine Herpesvirus ◽  
Vaccine Virus ◽  
Parental Virus ◽  
Wild Type Virus ◽  
Wild Type ◽  
Glycoprotein E ◽  
Virus Shedding ◽  
Virus Challenge ◽  
Herpesvirus Type

The authors previously reported the construction of a glycoprotein E-deleted (gE-) mutant of bovine herpesvirus type 1.2a (BHV-1.2a). This mutant, 265gE-, was designed as a vaccinal strain for differential vaccines, allowing the distinction between vaccinated and naturally infected cattle. In order to determine the safety and efficacy of this candidate vaccine virus, a group of calves was inoculated with 265gE-. The virus was detected in secretions of inoculated calves to lower titres and for a shorter period than the parental virus inoculated in control calves. Twenty one days after inoculation, the calves were challenged with the wild type parental virus. Only mild signs of infection were detected on vaccinated calves, whereas non-vaccinated controls displayed intense rhinotracheitis and shed virus for longer and to higher titres than vaccinated calves. Six months after vaccination, both vaccinated and control groups were subjected to reactivation of potentially latent virus. The mutant 265gE- could not be reactivated from vaccinated calves. The clinical signs observed, following the reactivation of the parental virus, were again much milder on vaccinated than on non-vaccinated calves. Moreover, parental virus shedding was considerably reduced on vaccinated calves at reactivation. In view of its attenuation, immunogenicity and protective effect upon challenge and reactivation with a virulent BHV-1, the mutant 265gE- was shown to be suitable for use as a BHV-1 differential vaccine virus.

scholarly journals Enhanced Influenza Virus-Like Particle Vaccines Containing the Extracellular Domain of Matrix Protein 2 and a Toll-Like Receptor Ligand

2012 ◽  
Vol 19 (8) ◽  
pp. 1119-1125 ◽  
Author(s):  
Bao-Zhong Wang ◽  
Harvinder S. Gill ◽  
Sang-Moo Kang ◽  
Li Wang ◽  
Ying-Chun Wang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Fusion Protein ◽  
Influenza A ◽  
Matrix Protein ◽  
Protective Efficacy ◽  
Extracellular Domain ◽  
Toll Like Receptor ◽  
Influenza A Viruses ◽  
Live Virus ◽  
Content Type

ABSTRACTThe extracellular domain of matrix protein 2 (M2e) is conserved among influenza A viruses. The goal of this project is to develop enhanced influenza vaccines with broad protective efficacy using the M2e antigen. We designed a membrane-anchored fusion protein by replacing the hyperimmunogenic region ofSalmonella entericaserovar Typhimurium flagellin (FliC) with four repeats of M2e (4.M2e-tFliC) and fusing it to a membrane anchor from influenza virus hemagglutinin (HA). The fusion protein was incorporated into influenza virus M1-based virus-like particles (VLPs). These VLPs retained Toll-like receptor 5 (TLR5) agonist activity comparable to that of soluble FliC. Mice immunized with the VLPs by either intramuscular or intranasal immunization showed high levels of systemic M2-specific antibody responses compared to the responses to soluble 4.M2e protein. High mucosal antibody titers were also induced in intranasally immunized mice. All intranasally immunized mice survived lethal challenges with live virus, while intramuscularly immunized mice showed only partial protection, revealing better protection by the intranasal route. These results indicate that a combination of M2e antigens and TLR ligand adjuvants in VLPs has potential for development of a broadly protective influenza A virus vaccine.

scholarly journals Strain-dependent effects of PB1-F2 of triple-reassortant H3N2 influenza viruses in swine

2012 ◽  
Vol 93 (10) ◽  
pp. 2204-2214 ◽  
Author(s):  
Lindomar Pena ◽  
Amy L. Vincent ◽  
Crystal L. Loving ◽  
Jamie N. Henningson ◽  
Kelly M. Lager ◽  
...  
Keyword(s):  
Virus Replication ◽  
Influenza A ◽  
Reverse Genetics ◽  
Influenza Viruses ◽  
Dependent Manner ◽  
Lung Pathology ◽  
Influenza A Viruses ◽  
Virus Shedding ◽  
The Impact ◽  
Strain Dependent

The PB1-F2 protein of the influenza A viruses (IAVs) can act as a virulence factor in mice. Its contribution to the virulence of IAV in swine, however, remains largely unexplored. In this study, we chose two genetically related H3N2 triple-reassortant IAVs to assess the impact of PB1-F2 in virus replication and virulence in pigs. Using reverse genetics, we disrupted the PB1-F2 ORF of A/swine/Wisconsin/14094/99 (H3N2) (Sw/99) and A/turkey/Ohio/313053/04 (H3N2) (Ty/04). Removing the PB1-F2 ORF led to increased expression of PB1-N40 in a strain-dependent manner. Ablation of the PB1-F2 ORF (or incorporation of the N66S mutation in the PB1-F2 ORF, Sw/99 N66S) affected the replication in porcine alveolar macrophages of only the Sw/99 KO (PB1-F2 knockout) and Sw/99 N66S variants. The Ty/04 KO strain showed decreased virus replication in swine respiratory explants, whereas no such effect was observed in Sw/99 KO, compared with the wild-type (WT) counterparts. In pigs, PB1-F2 did not affect virus shedding or viral load in the lungs for any of these strains. Upon necropsy, PB1-F2 had no effect on the lung pathology caused by Sw/99 variants. Interestingly, the Ty/04 KO-infected pigs showed significantly increased lung pathology at 3 days post-infection compared with pigs infected with the Ty/04 WT strain. In addition, the pulmonary levels of interleukin (IL)-6, IL-8 and gamma interferon were regulated differentially by the expression of PB1-F2. Taken together, these results indicate that PB1-F2 modulates virus replication, virulence and innate immune responses in pigs in a strain-dependent fashion.

scholarly journals Protective efficacy of RIT 4025, a live attenuated influenza vaccine strain, and evaluation of heterotypic immunity to influenza A viruses in ferrets

1977 ◽  
Vol 79 (2) ◽  
pp. 203-208 ◽  
Author(s):  
A. Delem
Keyword(s):  
Animal Model ◽  
Vaccine Strain ◽  
Influenza A ◽  
Protective Efficacy ◽  
Wild Strain ◽  
Influenza A Viruses ◽  
Challenge Inoculation ◽  
Virus Shedding ◽  
Live Attenuated Influenza Vaccine ◽  
Homologous Strain

SUMMARYFerrets immunized with an H3N2 recombinant of A/PR/8/34 and A/Scotland/ 840f74 (RIT 4025 vaccine strain) were almost completely protected against a challenge with the homologous strain A/Scotland/ 840/ 74. The protection was lower but highly significant when the challenge was performed with the heterologous A/Victoria/3f75 wild strain. The protection afforded by the vaccine strain was measured by three indicators: absence of temperature rise, absence or reduction of virus shedding and absence or reduction of nasal protein increase when compared with uninoculated controls.Heterotypic immunity in this animal model was not significant when these three indicators were measured after a challenge inoculation performed 5 weeks after immunization.

scholarly journals Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model

2007 ◽  
Vol 81 (13) ◽  
pp. 6890-6898 ◽  
Author(s):  
Hui-Ling Yen ◽  
Aleksandr S. Lipatov ◽  
Natalia A. Ilyushina ◽  
Elena A. Govorkova ◽  
John Franks ◽  
...  
Keyword(s):  
Hong Kong ◽  
Binding Affinity ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Clinical Signs ◽  
Influenza Viruses ◽  
Contact Model ◽  
Virus Shedding ◽  
H5n1 Influenza

ABSTRACT The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with α2,3 or α2,6 linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess “avian-like” α2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets inoculated with 103 50% tissue culture infectious doses. A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for “human-like” α2,6-linked SA receptors in addition to their affinity for α2,3-linked SA receptors, caused mild clinical symptoms and were not lethal to the ferrets. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected. One contact ferret developed neutralizing antibodies to A/Hong Kong/213/03 but did not exhibit any clinical signs or detectable virus shedding. In two groups, one of two naïve contact ferrets had detectable virus after 6 to 8 days when housed together with the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed severe clinical signs, although little or no virus was detected in nasal washes. This limited virus shedding explained the absence of secondary transmission from the infected contact ferret to the other naïve ferret that were housed together. Our results suggest that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species.

Pathological Lesions in the Lungs of Ducks Infected with Influenza A Viruses

1989 ◽  
Vol 26 (1) ◽  
pp. 1-5 ◽  
Author(s):  
A. J. Cooley ◽  
H. Van Campen ◽  
M. S. Philpott ◽  
B. C. Easterday ◽  
V. S. Hinshaw
Keyword(s):  
Monoclonal Antibodies ◽  
Respiratory Tract ◽  
Influenza A ◽  
Infectious Virus ◽  
Histopathological Examination ◽  
Clinical Signs ◽  
Immunoperoxidase Staining ◽  
Influenza A Viruses ◽  
Pathological Lesions ◽  
Viral Antigens

To determine histopathological damage in the respiratory tract, ducks were inoculated with five different influenza A viruses, including viruses virulent for other avian hosts. Lungs were collected for detection of virus and histopathological examination. Small amounts of infectious virus were recovered from lungs, and viral antigens were demonstrated by immunoperoxidase staining with monoclonal antibodies to the viral nucleoprotein. Although clinical signs were not detected, lungs of ducks infected with both virulent and avirulent viruses had mild pneumonia characterized by infiltrates of lymphocytes and macrophages. These findings show that although clinical signs are not evident, ducks may have damage to the respiratory tract during influenza.

scholarly journals Porcine Reproductive and Respiratory Syndrome Modified Live Virus Vaccine: A “Leaky” Vaccine with Debatable Efficacy and Safety

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 362
Author(s):  
Lei Zhou ◽  
Xinna Ge ◽  
Hanchun Yang
Keyword(s):  
Immune Response ◽  
Antigenic Variation ◽  
Safety Issue ◽  
Clinical Signs ◽  
Virus Transmission ◽  
The United States ◽  
Production Performance ◽  
Live Virus ◽  
Virus Shedding ◽  
Prrs Virus

Porcine reproductive and respiratory syndrome (PRRS) caused by the PRRS virus (PRRSV) is one of the most economically important diseases, that has significantly impacted the global pork industry for over three decades, since it was first recognized in the United States in the late 1980s. Attributed to the PRRSV extensive genetic and antigenic variation and rapid mutability and evolution, nearly worldwide epidemics have been sustained by a set of emerging and re-emerging virus strains. Since the first modified live virus (MLV) vaccine was commercially available, it has been widely used for more than 20 years, for preventing and controlling PRRS. On the one hand, MLV can induce a protective immune response against homologous viruses by lightening the clinical signs of pigs and reducing the virus transmission in the affected herd, as well as helping to cost-effectively increase the production performance on pig farms affected by heterologous viruses. On the other hand, MLV can still replicate in the host, inducing viremia and virus shedding, and it fails to confer sterilizing immunity against PRRSV infection, that may accelerate viral mutation or recombination to adapt the host and to escape from the immune response, raising the risk of reversion to virulence. The unsatisfied heterologous cross-protection and safety issue of MLV are two debatable characterizations, which raise the concerns that whether it is necessary or valuable to use this leaky vaccine to protect the field viruses with a high probability of being heterologous. To provide better insights into the immune protection and safety related to MLV, recent advances and opinions on PRRSV attenuation, protection efficacy, immunosuppression, recombination, and reversion to virulence are reviewed here, hoping to give a more comprehensive recognition on MLV and to motivate scientific inspiration on novel strategies and approaches of developing the next generation of PRRS vaccine.

scholarly journals Swine influenza: Newer data on diagnosis, interpretation of the results, and control

2021 ◽  
Vol 77 (02) ◽  
pp. 6506-2021
Author(s):  
ZYGMUNT PEJSAK ◽  
KAZIMIERZ TARASIUK
Keyword(s):  
Influenza A ◽  
Bacterial Infections ◽  
Clinical Signs ◽  
Swine Influenza ◽  
Water System ◽  
Influenza Viruses ◽  
Upper Respiratory Tract ◽  
Influenza A Viruses ◽  
Serological Tests ◽  
Specific Antibodies

Influenza viruses are among the major causes of acute respiratory disease outbreaks in pigs. In most cases, infections are subclinical. Until 2009, three subtypes of IAV-S circulated in the pig population in Europe, with some geographical restrictions regarding their prevalence: avian-like (av) H1N1, reassortant (r) H3N2, and human (hu) H1N2. Viruses of the H1N1av lineage appeared to be responsible for the majority of swine infections in Europe. In 2009, a fourth subtype entered the pig population: the human pandemic H1N1 2009 influenza A virus (H1N1pdm). Due to the expression of receptors with α-2-6 or α-2-3-linked terminal sialic acids in the porcine upper respiratory tract, swine appear to be susceptible to influenza A viruses of both avian and human origin. A clinical diagnosis of swine influenza is not easy, since there are no observable pathognomonic clinical signs, and the disease must be distinguished from a variety of other respiratory conditions in pigs. A final diagnosis can be made by the following methods: detection of viral proteins or nucleic acid, isolation of virus, or demonstration of virus-specific antibodies. IAV-S is most likely to be found in nasal and pharyngeal secretions during the fever period of illness. Serological tests are used to demonstrate the presence of influenza-specific antibodies. Serology is the most useful technique to determine the immune status of the herd, to assess the levels of maternally derived antibodies in young piglets and their profile, as well as post-vaccination antibody titers, and to perform pre-movement testing of pigs. The interpretation of serological data is often complex and may be further confounded by concurrent circulation of different virus subtypes and gene lineages. In control of IAV-S, vaccination appears to be the primary tool for preventing influenza. The efficacy of vaccination may be various and is correlated with homology between vaccine and field IAV-S strains. There is no treatment available for IAV-S. The administration of aspirin via the water system or of paracetamol in feed may play a role as a support therapy. To avoid subsequent bacterial infections, treatment with an antibiotic is essential.

scholarly journals Structures and functions linked to genome-wide adaptation of human influenza A viruses

2018 ◽  
Author(s):  
Thorsten R. Klingen ◽  
Jens Loers ◽  
Stephanie Stanelle-Bertram ◽  
Gülsah Gabriel ◽  
Alice C. McHardy
Keyword(s):  
Influenza A ◽  
Inflammatory Responses ◽  
Respiratory Infections ◽  
Protein Structures ◽  
Antiviral Drug ◽  
Human Influenza ◽  
Influenza A Viruses ◽  
Mortality And Morbidity ◽  
Evolutionary Forces ◽  
Genome Wide

AbstractHuman influenza A viruses elicit short-term respiratory infections with considerable mortality and morbidity. While H3N2 viruses circulate since almost 50 years, the recent introduction of pH1N1 viruses presents an excellent opportunity for a comparative analysis of the genome-wide evolutionary forces acting on both subtypes. Here, we inferred patches of sites relevant for adaptation, i.e. being under positive selection, on eleven viral protein structures, from all available data since 1968 and correlated these with known functional properties. Overall, pH1N1 had more patches than H3N2 viruses, especially in the viral polymerase complex, while antigenic evolution is more apparent for H3N2 viruses. In both subtypes, NS1 had the highest patch and patch site frequency, indicating that NS1-mediated viral attenuation of host inflammatory responses is a continuously intensifying process, elevated even in the longtime-circulating subtype H3N2. We confirmed the resistance-causing effects of two pH1N1 changes against oseltamivir in NA activity assays, demonstrating the value of the resource for discovering functionally relevant changes. Our results represent an atlas of protein regions and sites with links to host adaptation, antiviral drug resistances and immune evasion for both subtypes for further study.

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