scholarly journals Comparative studies of infectivity, immunogenicity and cross-protective efficacy of live attenuated influenza vaccines containing nucleoprotein from cold-adapted or wild-type influenza virus in a mouse model

Virology ◽  
2017 ◽  
Vol 500 ◽  
pp. 209-217 ◽  
Author(s):  
Irina Isakova-Sivak ◽  
Daniil Korenkov ◽  
Tatiana Smolonogina ◽  
Tatiana Tretiak ◽  
Svetlana Donina ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Comparative Studies ◽  
Protective Efficacy ◽  
Influenza Vaccines ◽  
Wild Type ◽  
Cold Adapted

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 Sequence comparison of wild-type and cold-adapted B/Ann Arbor/1/66 influenza virus genes

Virology ◽  
1988 ◽  
Vol 163 (2) ◽  
pp. 429-443 ◽  
Author(s):  
Dan C. DeBorde ◽  
Armen M. Donabedian ◽  
M.Louise Herlocher ◽  
Clayton W. Naeve ◽  
Hunein F. Maassab
Keyword(s):  
Influenza Virus ◽  
Sequence Comparison ◽  
Wild Type ◽  
Cold Adapted ◽  
Ann Arbor

Inhibition of ciliary activity in organ cultures of ferret trachea in reference to genetic and biological characters of influenza virus strains

1982 ◽  
Vol 28 (7) ◽  
pp. 809-814 ◽  
Author(s):  
P. Diaz-Rodriguez ◽  
A. Boudreault
Keyword(s):  
Influenza Virus ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Ciliary Activity ◽  
Organ Cultures ◽  
Preliminary Screening ◽  
Cold Adapted ◽  
Activity Inhibition ◽  
Biological Characters ◽  
Virus Strains

As reported previously, attenuated stable inhibitor-resistant influenza viruses can be screened by a 50% ciliary activity inhibition test in ferret tracheal organ cultures. This test was further applied to 5 attenuated cold-adapted influenza strains and to 11 strains with known a percentage of RNA–RNA hybridization with the parental A/PR/8/34 (H0N1) virus strain. Again, with one exception, attenuated strains could be clearly differentiated from virulent ones. It was concluded that virulence of influenza strains for man can be detected using this test regardless of the techniques used to prepare attenuated variants. A preliminary screening of attenuated candidates for live influenza vaccines can be achieved with confidence on ferret tracheal organ cultures.

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 Immunogenicity and Protective Efficacy of Seasonal Human Live Attenuated Cold-Adapted Influenza Virus Vaccine in Pigs

2019 ◽  
Vol 10 ◽  
Author(s):  
Barbara Holzer ◽  
Sophie B. Morgan ◽  
Veronica Martini ◽  
Rajni Sharma ◽  
Becky Clark ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Vaccine ◽  
Protective Efficacy ◽  
Influenza Virus Vaccine ◽  
Cold Adapted

scholarly journals African Green Monkeys Recapitulate the Clinical Experience with Replication of Live Attenuated Pandemic Influenza Virus Vaccine Candidates

2014 ◽  
Vol 88 (14) ◽  
pp. 8139-8152 ◽  
Author(s):  
Yumiko Matsuoka ◽  
Amorsolo Suguitan ◽  
Marlene Orandle ◽  
Myeisha Paskel ◽  
Kobporn Boonnak ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Animal Models ◽  
Avian Influenza ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Nonhuman Primate ◽  
Protective Efficacy ◽  
Wild Type ◽  
Vaccine Candidates ◽  
Green Monkeys

ABSTRACTLive attenuated cold-adapted (ca) H5N1, H7N3, H6N1, and H9N2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. However, when these vaccine candidates were evaluated in phase I clinical trials, there were inconsistencies between the observations in animal models and in humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative with respect to the vaccine viruses before vaccination. Therefore, we sought a model that would better reflect the findings in humans and evaluated African green monkeys (AGMs) as a nonhuman primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to that in humans. We evaluated the replication ofwtandcaviruses of avian influenza (AI) virus subtypes H5N1, H6N1, H7N3, and H9N2 in the respiratory tract of AGMs. All of thewtviruses replicated efficiently, while replication of thecavaccine viruses was restricted to the upper respiratory tract. Interestingly, the patterns and sites of virus replication differed among the different subtypes. We also evaluated the immunogenicity and protective efficacy of H5N1, H6N1, H7N3, and H9N2cavaccines. Protection fromwtvirus challenge correlated well with the level of serum neutralizing antibodies. Immune responses were slightly better when vaccine was delivered by both intranasal and intratracheal delivery than when it was delivered intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects and that AGMs may be a useful model to evaluate the replication ofcavaccine candidates.IMPORTANCEFerrets and mice are commonly used for preclinical evaluation of influenza vaccines. However, we observed significant inconsistencies between observations in humans and in these animal models. We used African green monkeys (AGMs) as a nonhuman primate (NHP) model for a comprehensive and comparative evaluation of pairs of wild-type and pandemic live attenuated influenza virus vaccines (pLAIV) representing four subtypes of avian influenza viruses and found that pLAIVs replicate similarly in AGMs and humans and that AGMs can be useful for evaluation of the protective efficacy of pLAIV.

scholarly journals Temperature-Sensitive Live-Attenuated Canine Influenza Virus H3N8 Vaccine

2016 ◽  
Vol 91 (4) ◽  
Author(s):  
Aitor Nogales ◽  
Laura Rodriguez ◽  
Caroline Chauché ◽  
Kai Huang ◽  
Emma C. Reilly ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Respiratory Pathogen ◽  
Temperature Sensitive ◽  
Wild Type ◽  
Canine Influenza Virus ◽  
Canine Influenza ◽  
Better Than

ABSTRACT Canine influenza is a respiratory disease of dogs caused by canine influenza virus (CIV). CIV subtypes responsible for influenza in dogs include H3N8, which originated from the transfer of H3N8 equine influenza virus to dogs; and the H3N2 CIV, which is an avian-origin virus that adapted to infect dogs. Influenza infections are most effectively prevented through vaccination to reduce transmission and future infection. Currently, only inactivated influenza vaccines (IIVs) are available for the prevention of CIV in dogs. However, the efficacy of IIVs is suboptimal, and novel approaches are necessary for the prevention of disease caused by this canine respiratory pathogen. Using reverse genetics techniques, we have developed a live-attenuated CIV vaccine (LACIV) for the prevention of H3N8 CIV. The H3N8 LACIV replicates efficiently in canine cells at 33°C but is impaired at temperatures of 37 to 39°C and was attenuated compared to wild-type H3N8 CIV in vivo and ex vivo. The LACIV was able to induce protection against H3N8 CIV challenge with a single intranasal inoculation in mice. Immunogenicity and protection efficacy were better than that observed with a commercial CIV H3N8 IIV but provided limited cross-reactive immunity and heterologous protection against H3N2 CIV. These results demonstrate the feasibility of implementing a LAIV approach for the prevention and control of H3N8 CIV in dogs and suggest the need for a new LAIV for the control of H3N2 CIV. IMPORTANCE Two influenza A virus subtypes has been reported in dogs in the last 16 years: the canine influenza viruses (CIV) H3N8 and H3N2 of equine and avian origins, respectively. To date, only inactivated influenza vaccines (IIVs) are available to prevent CIV infections. Here, we report the generation of a recombinant, temperature-sensitive H3N8 CIV as a live-attenuated influenza vaccine (LAIV), which was attenuated in mice and dog tracheal, explants compared to CIV H3N8 wild type. A single dose of H3N8 LACIV showed immunogenicity and protection against a homologous challenge that was better than that conferred with an H3N8 IIV, demonstrating the feasibility of implementing a LAIV approach for the improved control of H3N8 CIV infections in dogs.

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