scholarly journals Impact of Individual Viral Gene Segments from Influenza A/H5N8 Virus on the Protective Efficacy of Inactivated Subtype-Specific Influenza Vaccine

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 368
Author(s):  
Yassmin Moatasim ◽  
Ahmed Kandeil ◽  
Ahmed Mostafa ◽  
Omnia Kutkat ◽  
Mohamed El Sayes ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Influenza A ◽  
Reverse Genetics ◽  
Protective Efficacy ◽  
Economic Losses ◽  
Viral Gene ◽  
Highly Pathogenic ◽  
H5n8 Virus ◽  
Antigenic Proteins ◽  
The Individual

Since its emergence in 2014, the highly pathogenic avian influenza H5N8 virus has continuously and rapidly spread worldwide in the poultry sector resulting in huge economic losses. A typical inactivated H5N8 vaccine is prepared using the six internal genes from A/PR8/1934 (H1N1) and the two major antigenic proteins (HA and NA) from the circulating H5N8 strain with the HA modified to a low pathogenic form (PR8HA/NA-H5N8). The contribution of the other internal proteins from H5N8, either individually or in combination, to the overall protective efficacy of PR8-based H5N8 vaccine has not been investigated. Using reverse genetics, a set of PR8-based vaccines expressing the individual proteins from an H5N8 strain were rescued and compared to the parent PR8 and low pathogenic H5N8 strains and the commonly used PR8HA/NA-H5N8. Except for the PR8-based vaccine strains expressing the HA of H5N8, none of the rescued combinations could efficiently elicit virus-neutralizing antibodies. Compared to PR8, the non-HA viral proteins provided some protection to infected chickens six days post infection. We assume that this late protection was related to cell-based immunity rather than antibody-mediated immunity. This may explain the slight advantage of using full low pathogenic H5N8 instead of PR8HA/NA-H5N8 to improve protection by both the innate and the humoral arms of the immune system.

scholarly journals Protective Efficacy of an Orf Virus-Vector Encoding the Hemagglutinin and the Nucleoprotein of Influenza A Virus in Swine

2021 ◽  
Vol 12 ◽  
Author(s):  
Lok R. Joshi ◽  
David Knudsen ◽  
Pablo Piñeyro ◽  
Santosh Dhakal ◽  
Gourapura J. Renukaradhya ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Swine Influenza Virus ◽  
Swine Influenza ◽  
Challenge Infection ◽  
Viral Rna ◽  
Economic Losses ◽  
Recombinant Viruses

Swine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses challenges to public health given its zoonotic potential. Thus effective IAV-S vaccines are needed and highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs, with higher levels of neutralizing antibodies (NA) being detected in OV-HA-NP-immunized animals pre-challenge infection. Although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S-specific proliferating CD8+ T cells upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in incremental protection against challenge infection as evidenced by a reduced secondary antibody response (NA and HI antibodies) following IAV-S challenge and reduced virus shedding in nasal secretions (lower viral RNA loads and frequency of animals shedding viral RNA and infectious virus), when compared to animals in the OV-HA group. Interestingly, broader cross neutralization activity was also observed in serum of OV-HA-NP-immunized animals against a panel of contemporary IAV-S isolates representing the major genetic clades circulating in swine. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.

scholarly journals Cell Culture-Derived Tilapia Lake Virus-Inactivated Vaccine Containing Montanide Adjuvant Provides High Protection against Viral Challenge for Tilapia

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 86
Author(s):  
Weiwei Zeng ◽  
Yingying Wang ◽  
Huzi Hu ◽  
Qing Wang ◽  
Sven M. Bergmann ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Interferon Γ ◽  
Economic Losses ◽  
Mrna Levels ◽  
Infectious Dose ◽  
Booster Immunization ◽  
Virus Challenge ◽  
High Level ◽  
Factor Α

Tilapia lake virus (TiLV) is a newly emerging pathogen responsible for high mortality and economic losses in the global tilapia industry. Currently, no antiviral therapy or vaccines are available for the control of this disease. The goal of the present study was to evaluate the immunological effects and protective efficacy of formaldehyde- and β-propiolactone-inactivated vaccines against TiLV in the presence and absence of the Montanide IMS 1312 VG adjuvant in tilapia. We found that β-propiolactone inactivation of viral particles generated a vaccine with a higher protection efficacy against virus challenge than did formaldehyde. The relative percent survivals of vaccinated fish at doses of 108, 107, and 106 50% tissue culture infectious dose (TCID50)/mL were 42.9%, 28.5%, and 14.3% in the absence of the adjuvant and 85.7%, 64.3%, and 32.1% in its presence, respectively. The vaccine generated specific IgM and neutralizing antibodies against TiLV at 3 weeks following immunization that were significantly increased after a second booster immunization. The steady state mRNA levels of the genes tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interferon γ (IFN-γ), cluster of differentiation 4 (CD4), major histocompatibility complex (MHC)-Ia, and MHC-II were all increased and indicated successful immune stimulation against TiLV. The vaccine also significantly lowered the viral loads and resulted in significant increases in survival, indicating that the vaccine may also inhibit viral proliferation as well as stimulate a protective antibody response. The β-propiolactone-inactivated TiLV vaccine coupled with the adjuvant Montanide IMS 1312 VG and booster immunizations can provide a high level of protection from virus challenge in tilapia.

scholarly journals Structural and molecular basis for foot-and-mouth disease virus neutralization by two potent protective antibodies

2021 ◽  
Author(s):  
Hu Dong ◽  
Pan Liu ◽  
Manyuan Bai ◽  
Kang Wang ◽  
Rui Feng ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Foot And Mouth Disease ◽  
Therapeutic Benefit ◽  
Mouth Disease ◽  
Economic Losses ◽  
Viral Particles ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Protective Antibodies

Outbreaks of Foot-and-mouth disease (FMD) caused by FMD virus result in significant economic losses. Vaccination is helpful, but the benefits are diminished with antigenic diversity within serotypes, instability of the immunogen and inability to confer protection for long durations. Here we have further dissected the mechanisms underpinning the protective efficacy of two previously reported neutralizing antibodies (NAbs), M8 and M170. The atomic details of the epitopes of M8 and M170 unveiled suggest that protection is conferred by disrupting the virus-receptor interactions. Consequently, administration of these NAbs conferred prophylactic and therapeutic benefit in guinea pigs, raising the possibility of administering NAbs before or during vaccination to confer immediate protection; well before the bolstering of the immune response by the vaccine. Differences in the residues and the conformation of elements making up the epitopes explain the differences in specificities of M8 and M170. An ability to bind 146S viral particles specifically, but not 12S degraded components, highlights a likely role for M170 in the quality control of vaccines.

scholarly journals Cloning recombinant pHW2000 vector carrying the HA gene for preparation of the primary influenza A/H5N1 vaccine strain

2017 ◽  
Vol 33 (1S) ◽  
Author(s):  
Nguyen Thi Thu Hang ◽  
Hoang Thi Thu Hang ◽  
Nguyen Hung Chi ◽  
Chu Hoang Ha ◽  
Nguyen Trung Nam
Keyword(s):  
Amino Acids ◽  
Avian Influenza ◽  
Influenza A ◽  
Reverse Genetics ◽  
Genetic Relationships ◽  
Highly Pathogenic ◽  
Ha Gene ◽  
H5n1 Influenza ◽  
Hpai H5n1 ◽  
Clade 2.3.2.1C

Influenza A/H5N1 virus evolves rapidly and generate new variants, therefore it is essential to develop effective vaccines against the currently circulating influenza strains. Among clades and subclades of highly pathogenic avian influenza (HPAI) H5N1 viruses circulating in Vietnam, H5N1 clade 1.1 and clade 2.3.2.1c possess genetic relationships to many strains of influenza; thus they are suggested to be used for producing vaccines against avian influenza. In this article, two HA gene segments of two types of A/H5N1 influenza clade have been designed: HA clade 1.1 gene consists 1825 nucleotides encoding 565 amino acids, HA clade 2.3.2.1c gene consists 1822 nucleotides, encoding 564 amino acids. Most importantly, nucleotide sequence of the pathogenic region of HA was removed. Each of the two HA segments corresponding to the two clades were successfully cloned into pHW2000 vector and will be used as a candidate for production of avian influenza vaccines using reverse genetics technique.  

scholarly journals A Host-Restricted Self-Attenuated Influenza Virus Provides Broad Pan-Influenza A Protection in a Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Minjin Kim ◽  
Yucheol Cheong ◽  
Jinhee Lee ◽  
Jongkwan Lim ◽  
Sanguine Byun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Infection Model ◽  
Wild Type ◽  
Group 1

Influenza virus infections can cause a broad range of symptoms, form mild respiratory problems to severe and fatal complications. While influenza virus poses a global health threat, the frequent antigenic change often significantly compromises the protective efficacy of seasonal vaccines, further increasing the vulnerability to viral infection. Therefore, it is in great need to employ strategies for the development of universal influenza vaccines (UIVs) which can elicit broad protection against diverse influenza viruses. Using a mouse infection model, we examined the breadth of protection of the caspase-triggered live attenuated influenza vaccine (ctLAIV), which was self-attenuated by the host caspase-dependent cleavage of internal viral proteins. A single vaccination in mice induced a broad reactive antibody response against four different influenza viruses, H1 and rH5 (HA group 1) and H3 and rH7 subtypes (HA group 2). Notably, despite the lack of detectable neutralizing antibodies, the vaccination provided heterosubtypic protection against the lethal challenge with the viruses. Sterile protection was confirmed by the complete absence of viral titers in the lungs and nasal turbinates after the challenge. Antibody-dependent cellular cytotoxicity (ADCC) activities of non-neutralizing antibodies contributed to cross-protection. The cross-protection remained robust even after in vivo depletion of T cells or NK cells, reflecting the strength and breadth of the antibody-dependent effector function. The robust mucosal secretion of sIgA reflects an additional level of cross-protection. Our data show that the host-restricted designer vaccine serves an option for developing a UIV, providing pan-influenza A protection against both group 1 and 2 influenza viruses. The present results of potency and breadth of protection from wild type and reassortant viruses addressed in the mouse model by single immunization merits further confirmation and validation, preferably in clinically relevant ferret models with wild type challenges.

scholarly journals Deaths among Wild Birds during Highly Pathogenic Avian Influenza A(H5N8) Virus Outbreak, the Netherlands

2017 ◽  
Vol 23 (12) ◽  
pp. 2050-2054 ◽  
Author(s):  
Erik Kleyheeg ◽  
Roy Slaterus ◽  
Rogier Bodewes ◽  
Jolianne M. Rijks ◽  
Marcel A.H. Spierenburg ◽  
...  
Keyword(s):  
The Netherlands ◽  
Avian Influenza ◽  
Influenza A ◽  
Highly Pathogenic Avian Influenza ◽  
Wild Birds ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
H5n8 Virus

scholarly journals IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Yuval Avnir ◽  
Corey T. Watson ◽  
Jacob Glanville ◽  
Eric C. Peterson ◽  
Aimee S. Tallarico ◽  
...  
Keyword(s):  
B Cell ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Cell Function ◽  
Somatic Hypermutation ◽  
Population Level ◽  
Humoral Immune ◽  
Humoral Immune System ◽  
The Individual ◽  
Universal Influenza Vaccine

Abstract IGHV polymorphism provides a rich source of humoral immune system diversity. One important example is the IGHV1-69 germline gene where the biased use of alleles that encode the critical CDR-H2 Phe54 (F-alleles) to make broadly neutralizing antibodies (HV1-69-sBnAb) to the influenza A hemagglutinin stem domain has been clearly established. However, whether IGHV1-69 polymorphism can also modulate B cell function and Ab repertoire expression through promoter and copy number (CN) variations has not been reported, nor has whether IGHV1-69 allelic distribution is impacted by ethnicity. Here we studied a cohort of NIH H5N1 vaccinees and demonstrate for the first time the influence of IGHV1-69 polymorphism on V-segment usage, somatic hypermutation and B cell expansion that elucidates the dominance of F-alleles in HV1-69-sBnAbs. We provide evidence that Phe54/Leu54 (F/L) polymorphism correlates with shifted repertoire usage of other IGHV germline genes. In addition, we analyzed ethnically diverse individuals within the 1000 genomes project and discovered marked variations in F- and L- genotypes and CN among the various ethnic groups that may impact HV1-69-sBnAb responses. These results have immediate implications for understanding HV1-69-sBnAb responses at the individual and population level and for the design and implementation of “universal” influenza vaccine.

scholarly journals Multiple Reassorted Viruses as Cause of Highly Pathogenic Avian Influenza A(H5N8) Virus Epidemic, the Netherlands, 2016

2017 ◽  
Vol 23 (12) ◽  
pp. 1974-1981 ◽  
Author(s):  
Nancy Beerens ◽  
Rene Heutink ◽  
Saskia A. Bergervoet ◽  
Frank Harders ◽  
Alex Bossers ◽  
...  
Keyword(s):  
The Netherlands ◽  
Avian Influenza ◽  
Influenza A ◽  
Highly Pathogenic Avian Influenza ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
H5n8 Virus

scholarly journals Genetic Characterization of Highly Pathogenic Avian Influenza A(H5N8) Virus in Pakistani Live Bird Markets Reveals Rapid Diversification of Clade 2.3.4.4b Viruses

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1633
Author(s):  
Muzaffar Ali ◽  
Tahir Yaqub ◽  
Muhammad Furqan Shahid ◽  
Foong Ying Wong ◽  
Nadia Mukhtar ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Virus Detection ◽  
Human Infection ◽  
Economic Losses ◽  
Influenza Surveillance ◽  
Highly Pathogenic ◽  
Live Bird Markets ◽  
Domestic Poultry ◽  
Live Bird

The highly pathogenic (HPAI) avian influenza A(H5N1) viruses have undergone reassortment with multiple non-N1-subtype neuraminidase genes since 2008, leading to the emergence of H5Nx viruses. H5Nx viruses established themselves quickly in birds and disseminated from China to Africa, the Middle East, Europe and North America. Multiple genetic clades have successively evolved through frequent mutations and reassortment, posing a continuous threat to domestic poultry and causing substantial economic losses. Live bird markets are recognized as major sources of avian-to-human infection and for the emergence of zoonotic influenza. In Pakistan, the A(H5N1) virus was first reported in domestic birds in 2007; however, avian influenza surveillance is limited and there is a lack of knowledge on the evolution and transmission of the A(H5) virus in the country. We collected oropharyngeal swabs from domestic poultry and environmental samples from six different live bird markets during 2018–2019. We detected and sequenced HPAI A(H5N8) viruses from two chickens, one quail and one environmental sample in two markets. Temporal phylogenetics indicated that all novel HPAI A(H5N8) viruses belonged to clade 2.3.4.4b, with all eight genes of Pakistan A(H5N8) viruses most closely related to 2017 Saudi Arabia A(H5N8) viruses, which were likely introduced via cross-border transmission from neighboring regions approximately three months prior to virus detection into domestic poultry. Our data further revealed that clade 2.3.4.4b viruses underwent rapid lineage expansion in 2017 and acquired significant amino acid mutations, including mutations associated with increased haemagglutinin affinity to human α-2,6 receptors, prior to the first human A(H5N8) infection in Russian poultry workers in 2020. These results highlight the need for systematic avian influenza surveillance in live bird markets in Pakistan to monitor for potential A(H5Nx) variants that may arise from poultry populations.

Sign in / Sign up

Export Citation Format

Share Document