scholarly journals Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice

2015 ◽  
Vol 22 (6) ◽  
pp. 618-630 ◽  
Author(s):  
Wenling Wang ◽  
Renqing Li ◽  
Yao Deng ◽  
Ning Lu ◽  
Hong Chen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Strain ◽  
Influenza A ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Influenza Vaccines ◽  
Strong Immune Response ◽  
Influenza Virus Strain ◽  
Vaccinia Viruses ◽  
Viral Components

ABSTRACTThe conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD50) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD50and 10 LD50and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics.

scholarly journals A non-neutralizing antibody broadly protects against influenza virus infection by engaging effector cells

2021 ◽  
Vol 17 (8) ◽  
pp. e1009724
Author(s):  
Yi-An Ko ◽  
Yueh-Hsiang Yu ◽  
Yen-Fei Wu ◽  
Yung-Chieh Tseng ◽  
Chia-Lin Chen ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Influenza Virus Infection ◽  
Neutralizing Antibody ◽  
H1n1 Influenza ◽  
Influenza A Viruses

Hemagglutinin (HA) is the immunodominant protein of the influenza virus. We previously showed that mice injected with a monoglycosylated influenza A HA (HAmg) produced cross-strain-reactive antibodies and were better protected than mice injected with a fully glycosylated HA (HAfg) during lethal dose challenge. We employed a single B-cell screening platform to isolate the cross-protective monoclonal antibody (mAb) 651 from mice immunized with the HAmg of A/Brisbane/59/2007 (H1N1) influenza virus (Bris/07). The mAb 651 recognized the head domain of a broad spectrum of HAs from groups 1 and 2 influenza A viruses and offered prophylactic and therapeutic efficacy against A/California/07/2009 (H1N1) (Cal/09) and Bris/07 infections in mice. The antibody did not possess neutralizing activity; however, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis mediated by natural killer cells and alveolar macrophages were important in the protective efficacy of mAb 651. Together, this study highlighted the significance of effector functions for non-neutralizing antibodies to exhibit protection against influenza virus infection.

scholarly journals Avian influenza A(H5N1) in humans in Vietnam and poultry in Asia

2004 ◽  
Vol 8 (3) ◽  
Author(s):  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Virus Strain ◽  
Influenza A ◽  
The Past ◽  
Influenza Virus Strain

Avian influenza virus strain A(H5N1), which normally infects only birds, has been found in samples from 3 human patients in Vietnam in the past week

scholarly journals MiRNA Targeted NP Genome of Live Attenuated Influenza Vaccines Provide Cross-Protection against a Lethal Influenza Virus Infection

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 65
Author(s):  
Feixia Gao ◽  
Tianhan Yang ◽  
Xueying Liu ◽  
Feifei Xiong ◽  
Jian Luo ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Mirna Target ◽  
Protective Efficacy ◽  
Influenza Virus Infection ◽  
Cross Protection ◽  
Influenza Vaccines ◽  
Temperature Sensitive ◽  
Dependent Manner ◽  
Target Sites

The miRNA-based strategy has been used to develop live attenuated influenza vaccines. In this study, the nucleoprotein (NP) genome segment of the influenza virus was inserted by different perfect miRNA-192-5p target sites, and the virus was rescued by standard reverse genetics method, so as to verify the virulence and protective efficacy of live attenuated vaccine in cells and mice. The results showed there was no significant attenuation in 192t virus with one perfect miRNA-192-5p target site, and 192t-3 virus with three perfect miRNA target sites. However, 192t-6 virus with 6 perfect miRNA target sites and 192t-9 virus with 9 perfect miRNA target sites were both significantly attenuated after infection, and their virulence were similar to that of temperature-sensitive (TS) influenza A virus (IAV) which is a temperature-sensitive live attenuated influenza vaccine. Mice were immunized with different doses of 192t-6, 192t-9, and TS IAV. Four weeks after immunization, the IgG in serum and IgA in lung homogenate were increased in the 192t-6, 192t-9, and TS IAV groups, and the numbers of IFN-γ secreting splenocytes were also increased in a dose-dependent manner. Finally, 192t-6, and 192t-9 can protect the mice against the challenge of homologous PR8 H1N1 virus and heterosubtypic H3N2 influenza virus. MiRNA targeted viruses 192t-6 and 192t-9 were significantly attenuated and showed the same virulence as TS IAV and played a role in the cross-protection.

scholarly journals INDUCTION OF CROSS-REACTIVE ANTIBODIES IN MICE IMMUNIZED WITH CONSERVED LINEAR B-CELL EPITOPES DERIVED FROM INFLUENZA A VIRUS NEURAMINIDASE

2019 ◽  
Author(s):  
I Sychev ◽  
P. Kopeikin ◽  
E. Tsvetkova ◽  
K. Cheredova ◽  
B. Milman ◽  
...  
Keyword(s):  
Weight Loss ◽  
Influenza Virus ◽  
B Cell ◽  
Influenza A Virus ◽  
Influenza A ◽  
Protective Efficacy ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
B Cell Epitopes ◽  
Linear B

Introduction. Influenza is a socially considerable infection annually causing profound damage to the populational health and economy. Vaccination is the most effective way to manage influenza and its complications. There are various vaccines against influenza, but their common drawback is the narrow specificity, need for annual virus strain renewal, not always good immunogenicity and effectiveness. In this regard, a close attention is paid to developing universal influenza vaccines aimed to induce cross-reactive factors of the immune response to the most conserved parts of viral proteins. Antibodies against neuraminidase (NA) are able to provide heterosubtypic protection, which is important due to potential threat from influenza viruses, with differed hemagglutinin and neuraminidase compared to the currently circulating viruses. The present study is aimed to search for new and analyze previously predicted linear NA B-cell epitopes, conserved among all subtypes of influenza A virus.Results. there were found out eight conserved linear B-cell epitopes were located around the neuraminidase active site, three of which (MNPNQKIITIGS, ILRTQESEC, and DNWKGSNRP) were synthesized de novo, conjugated with bovine serum albumin to be further used for mouse immunization. Serum IgG antibodies were detected by ELISA in immunized mice. Antibodies specifically bind to various influenza A viruses containing NA subtypes N1, N2, N3, and N9. Immunization with NA peptides provided no protection from profound weight loss after infection with lethal H1N1 influenza virus. However, all immunized mice survived during the observation period, while in control group survival rate was as low as 28.6%. Assessing the viral load in the lungs of mice infected with the H1N1 virus did not reveal differences in titers either on day 4 or 8 post-infection. Nevertheless, the protective effect lacked upon challenge with lethal H7N9 influenza virus: mortality, weight loss, and lung virus titers were comparable both in immunized and control mice.Conclusions. The data obtained uncovered cross-reactivity in anti-NA antibodies induced by immunization with NA peptides as well as protective efficacy against infection caused by the H1N1, but not H7N9 virus. Thus, these data are promising and indicate that linear B-cell NA epitopes can be used for design of epitope-directed influenza vaccines, but a deeper and full examination of specificity for conserved NA epitopes as well as optimized immunization schemes are necessary to achieve higher protective efficacy.

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 Influenza PB1-F2 Inhibits Avian MAVS Signaling

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 409
Author(s):  
Yanna Xiao ◽  
Danyel Evseev ◽  
Chase A. Stevens ◽  
Adam Moghrabi ◽  
Domingo Miranzo-Navarro ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A Virus ◽  
Virus Strain ◽  
Species Interactions ◽  
Influenza A ◽  
Promoter Activity ◽  
Interferon Beta ◽  
Influenza Infection ◽  
Adaptor Protein ◽  
Human Cells

RIG-I plays an essential role in the duck innate immune response to influenza infection. RIG-I engages the critical adaptor protein mitochondrial antiviral signaling (MAVS) to activate the downstream signaling pathway. The influenza A virus non-structural protein PB1-F2 interacts with MAVS in human cells to inhibit interferon production. As duck and human MAVS share only 28% amino acid similarity, it is not known whether the influenza virus can similarly inhibit MAVS signaling in avian cells. Using confocal microscopy we show that MAVS and the constitutively active N-terminal end of duck RIG-I (2CARD) co-localize in DF-1 cells, and duck MAVS is pulled down with GST-2CARD. We establish that either GST-2CARD, or duck MAVS can initiate innate signaling in chicken cells and their co-transfection augments interferon-beta promoter activity. Demonstrating the limits of cross-species interactions, duck RIG-I 2CARD initiates MAVS signaling in chicken cells, but works poorly in human cells. The D122A mutation of human 2CARD abrogates signaling by affecting MAVS engagement, and the reciprocal A120D mutation in duck 2CARD improves signaling in human cells. We show mitochondrial localization of PB1-F2 from influenza A virus strain A/Puerto Rico/8/1934 (H1N1; PR8), and its co-localization and co-immunoprecipitation with duck MAVS. PB1-F2 inhibits interferon-beta promoter activity induced by overexpression of either duck RIG-I 2CARD, full-length duck RIG-I, or duck MAVS. Finally, we show that the effect of PB1-F2 on mitochondria abrogates TRIM25-mediated ubiquitination of RIG-I CARD in both human and avian cells, while an NS1 variant from the PR8 influenza virus strain does not.

scholarly journals Near-Complete Genome Sequence of Avian Influenza Virus Strain A/mallard/Balkhash/6304/2014 (H1N1) from Kazakhstan

2019 ◽  
Vol 8 (18) ◽  
Author(s):  
Kobey Karamendin ◽  
Aidyn Kydyrmanov ◽  
Saule Asanova ◽  
Elizaveta Khan ◽  
Klara Daulbayeva ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Avian Influenza ◽  
Avian Influenza Virus ◽  
Virus Strain ◽  
Mallard Duck ◽  
Content Type ◽  
Influenza Virus Strain ◽  
Monitoring Study ◽  
Bird Monitoring ◽  
Eastern Kazakhstan

An avian influenza virus strain, A/mallard/Balkhash/6304/2014 (H1N1), was isolated during a wild bird monitoring study in Kazakhstan in 2014. The virus was isolated from a wild mallard duck (Anas platyrhynchos) in eastern Kazakhstan.

scholarly journals Potency of a vaccine prepared from A/swine/Hokkaido/2/1981 (H1N1) against A/Narita/1/2009 (H1N1) pandemic influenza virus strain

2013 ◽  
Vol 10 (1) ◽  
pp. 47 ◽  
Author(s):  
Masatoshi Okamatsu ◽  
Yoshihiro Sakoda ◽  
Takahiro Hiono ◽  
Naoki Yamamoto ◽  
Hiroshi Kida
Keyword(s):  
Influenza Virus ◽  
Virus Strain ◽  
Pandemic Influenza ◽  
H1n1 Pandemic ◽  
Influenza Virus Strain ◽  
2009 H1n1

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.

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