scholarly journals Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Vaccine ◽  
2007 ◽  
Vol 25 (32) ◽  
pp. 6028-6036 ◽  
Author(s):  
Otfried Kistner ◽  
M. Keith Howard ◽  
Martin Spruth ◽  
Walter Wodal ◽  
Peter Brühl ◽  
...  
Keyword(s):  
Cell Culture ◽  
Immune Responses ◽  
Virus Strain ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Virus H5n1 ◽  
H5n1 Vaccine

The URNA Genes of Herpesvirus Saimiri (Strain C488) Are Dispensable for Transformation of Human T Cells In Vitro

1999 ◽  
Vol 73 (12) ◽  
pp. 10551-10555 ◽  
Author(s):  
Armin Ensser ◽  
André Pfinder ◽  
Ingrid Müller-Fleckenstein ◽  
Bernhard Fleckenstein
Keyword(s):  
Cell Culture ◽  
Herpesvirus Saimiri ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Human T Cell ◽  
Human T Cells ◽  
Small Nuclear Rnas ◽  
T Cell Lines

ABSTRACT The herpesvirus saimiri strain C488 genome contains five genes for small nuclear RNAs, termed herpesvirus saimiri URNAs (or HSURs). Using a cosmid-based approach, all HSURs were precisely deleted from the genome. The mutant virus replicated at levels that were similar to those of wild-type viruses in OMK cells. Although the HSURs are expressed in wild-type virus-transformed human T-cell lines, the deletion does not affect viral transformation in cell culture.

Pre-clinical development of cell culture (Vero)-derived H5N1 pandemic vaccines

2008 ◽  
Vol 389 (5) ◽  
Author(s):  
M. Keith Howard ◽  
Otfried Kistner ◽  
P. Noel Barrett
Keyword(s):  
Cell Culture ◽  
High Yield ◽  
Wild Type Virus ◽  
Effective Vaccine ◽  
Type Virus ◽  
Wild Type ◽  
Yield Production ◽  
Homologous Virus ◽  
Clade 1 ◽  
Influenza H5n1

AbstractThe rapid spread of avian influenza (H5N1) and its transmission to humans has raised the possibility of an imminent pandemic and concerns over the ability of standard influenza vaccine production methods to supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains, produced at a variety of manufacturing scales, were demonstrated to be highly immunogenic in animal models without the need for adjuvant. The vaccines induce cross-neutralising antibodies and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from other clades. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high-yield production of a candidate pandemic vaccine.

scholarly journals Attenuation of V- or C-Defective Measles Viruses: Infection Control by the Inflammatory and Interferon Responses of Rhesus Monkeys

2008 ◽  
Vol 82 (11) ◽  
pp. 5359-5367 ◽  
Author(s):  
Patricia Devaux ◽  
Gregory Hodge ◽  
Michael B. McChesney ◽  
Roberto Cattaneo
Keyword(s):  
Immune Responses ◽  
Measles Virus ◽  
Mononuclear Cells ◽  
Interferon Response ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Adaptive Immune Responses ◽  
C Protein ◽  
Adaptive Immune

ABSTRACT Patients recruited in virus-based cancer clinical trials and immunocompromised individuals in need of vaccination would profit from viral strains with defined attenuation mechanisms. We generated measles virus (MV) strains defective for the expression of either the V protein, a modulator of the innate immune response, or the C protein, which has multiple functions. The virulence of these strains was compared with that of the parental wild-type MV in a natural host, Macaca mulatta. Skin rash, viremia, and the strength of the innate and adaptive immune responses were characterized in groups of six animals. Replication of V- or C-protein-defective viruses was short-lived and reached lower levels in peripheral blood mononuclear cells and lymphatic organs compared to the wild-type virus; none of the mutants reverted to the wild type. The neutralizing antibody titers and MV-specific T-cell responses were equivalent in monkeys infected with the viral strains tested, documenting strong adaptive immune responses. In contrast, the inflammatory response was better controlled by wild-type MV, as revealed by inhibition of interleukin-6 and tumor necrosis factor alpha transcription. The interferon response was also better controlled by the wild-type virus than by the defective viruses. Since V- and C-defective MVs induce strong adaptive immune responses while spreading less efficiently, they may be developed as vaccines for immunocompromised individuals. Moreover, MV unable to interact with single innate immunity proteins may be developed for preferential replication in tumors with specific contexts of vulnerability.

scholarly journals The NB Protein of Influenza B Virus Is Not Necessary for Virus Replication In Vitro

2003 ◽  
Vol 77 (10) ◽  
pp. 6050-6054 ◽  
Author(s):  
Masato Hatta ◽  
Yoshihiro Kawaoka
Keyword(s):  
Cell Culture ◽  
Virus Replication ◽  
Wild Type Virus ◽  
Influenza B Virus ◽  
Influenza B ◽  
Type Virus ◽  
Wild Type ◽  
B Virus

ABSTRACT The NB protein of influenza B virus is thought to function as an ion channel and therefore would be expected to have an essential function in viral replication. Because direct evidence for its absolute requirement in the viral life cycle is lacking, we generated NB knockout viruses by reverse genetics and tested their growth properties both in vitro and in vivo. Mutants not expressing NB replicated as efficiently as the wild-type virus in cell culture, whereas in mice they showed restricted growth compared with findings for the wild-type virus. Thus, the NB protein is not essential for influenza B virus replication in cell culture but promotes efficient growth in mice.

scholarly journals Plasminogen-Binding Activity of Neuraminidase Determines the Pathogenicity of Influenza A Virus

2001 ◽  
Vol 75 (19) ◽  
pp. 9297-9301 ◽  
Author(s):  
Hideo Goto ◽  
Krisna Wells ◽  
Ayato Takada ◽  
Yoshihiro Kawaoka
Keyword(s):  
Cell Culture ◽  
Influenza A ◽  
Binding Activity ◽  
Glycosylation Site ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
C Terminus ◽  
Viral Hemagglutinin

ABSTRACT When expressed in vitro, the neuraminidase (NA) of A/WSN/33 (WSN) virus binds and sequesters plasminogen on the cell surface, leading to enhanced cleavage of the viral hemagglutinin. To obtain direct evidence that the plasminogen-binding activity of the NA enhances the pathogenicity of WSN virus, we generated mutant viruses whose NAs lacked plasminogen-binding activity because of a mutation at the C terminus, from Lys to Arg or Leu. In the presence of trypsin, these mutant viruses replicated similarly to wild-type virus in cell culture. By contrast, in the presence of plasminogen, the mutant viruses failed to undergo multiple cycles of replication while the wild-type virus grew normally. The mutant viruses showed attenuated growth in mice and failed to grow at all in the brain. Furthermore, another mutant WSN virus, possessing an NA with a glycosylation site at position 130 (146 in N2 numbering), leading to the loss of neurovirulence, failed to grow in cell culture in the presence of plasminogen. We conclude that the plasminogen-binding activity of the WSN NA determines its pathogenicity in mice.

scholarly journals Immunogenicity and Cross Protection in Mice Afforded by Pandemic H1N1 Live Attenuated Influenza Vaccine Containing Wild-Type Nucleoprotein

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Andrey Rekstin ◽  
Irina Isakova-Sivak ◽  
Galina Petukhova ◽  
Daniil Korenkov ◽  
Igor Losev ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Wild Type Virus ◽  
Pandemic H1n1 ◽  
Type Virus ◽  
Wild Type ◽  
Live Attenuated Influenza Vaccine ◽  
Np Gene

Since conserved viral proteins of influenza virus, such as nucleoprotein (NP) and matrix 1 protein, are the main targets for virus-specific CD8+ cytotoxic T-lymphocytes (CTLs), we hypothesized that introduction of the NP gene of wild-type virus into the genome of vaccine reassortants could lead to better immunogenicity and afford better protection. This paper describes in vitro and in vivo preclinical studies of two new reassortants of pandemic H1N1 live attenuated influenza vaccine (LAIV) candidates. One had the hemagglutinin (HA) and neuraminidase (NA) genes from A/South Africa/3626/2013 H1N1 wild-type virus on the A/Leningrad/134/17/57 master donor virus backbone (6 : 2 formulation) while the second had the HA, NA, and NP genes of the wild-type virus on the same backbone (5 : 3 formulation). Although both LAIVs induced similar antibody immune responses, the 5 : 3 LAIV provoked greater production of virus-specific CTLs than the 6 : 2 variant. Furthermore, the 5 : 3 LAIV-induced CTLs had higher in vivo cytotoxic activity, compared to 6 : 2 LAIV. Finally, the 5 : 3 LAIV candidate afforded greater protection against infection and severe illness than the 6 : 2 LAIV. Inclusion in LAIV of the NP gene from wild-type influenza virus is a new approach to inducing cross-reactive cell-mediated immune responses and cross protection against pandemic influenza.

scholarly journals Influenza A Virus Lacking M2 Protein as a Live Attenuated Vaccine

2009 ◽  
Vol 83 (11) ◽  
pp. 5947-5950 ◽  
Author(s):  
Shinji Watanabe ◽  
Tokiko Watanabe ◽  
Yoshihiro Kawaoka
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Lethal Challenge ◽  
Live Attenuated Vaccine ◽  
Attenuated Vaccine ◽  
Live Attenuated Influenza Vaccine

ABSTRACT Mutant influenza virus that lacks the transmembrane and cytoplasmic tail domains of M2 (M2 knockout [M2KO]) is attenuated in both cell culture and mice. Here, we examined the potency of M2KO influenza virus as a live attenuated influenza vaccine. M2KO virus grew as efficiently as the wild-type virus in cells stably expressing the wild-type M2, indicating the feasibility of efficient vaccine production. Mice intranasally vaccinated with M2KO virus developed protective immune responses and survived a lethal challenge with the wild-type virus, suggesting that the M2KO virus has potential as a live attenuated vaccine.

scholarly journals Effects of Double Combinations of Amantadine, Oseltamivir, and Ribavirin on Influenza A (H5N1) Virus Infections in Cell Culture and in Mice

2009 ◽  
Vol 53 (5) ◽  
pp. 2120-2128 ◽  
Author(s):  
Donald F. Smee ◽  
Brett L. Hurst ◽  
Min-Hui Wong ◽  
Kevin W. Bailey ◽  
John D. Morrey
Keyword(s):  
Cell Culture ◽  
Virus Infection ◽  
Influenza A ◽  
H5n1 Virus ◽  
Active Form ◽  
Wild Type Virus ◽  
Type Virus ◽  
Resistant Virus ◽  
Wild Type ◽  
Oseltamivir Carboxylate

ABSTRACT An amantadine-resistant influenza A/Duck/MN/1525/81 (H5N1) virus was developed from the low-pathogenic North American wild-type (amantadine-sensitive) virus for studying treatment of infections in cell culture and in mice. Double combinations of amantadine, oseltamivir (or the cell culture-active form, oseltamivir carboxylate), and ribavirin were used. Amantadine-oseltamivir carboxylate and amantadine-ribavirin combinations showed synergistic interactions over a range of doses against wild-type virus in Madin-Darby canine kidney (MDCK) cell culture, but oseltamivir carboxylate-ribavirin combinations did not. Primarily additive interactions were seen with oseltamivir carboxylate-ribavirin combinations against amantadine-resistant virus. The presence of amantadine in drug combinations against the resistant virus did not improve activity. The wild-type and amantadine-resistant viruses were lethal to mice by intranasal instillation. The resistant virus infection could not be treated with amantadine up to 100 mg/kg body weight/day, whereas the wild-type virus infection was treatable with oral doses of 10 (weakly effective) to 100 mg/kg/day administered twice a day for 5 days starting 4 h prior to virus exposure. Drug combination studies showed that treatment of the amantadine-resistant virus infection with amantadine-oseltamivir or amantadine-ribavirin combinations was not significantly better than using oseltamivir or ribavirin alone. In contrast, the oseltamivir-ribavirin (25- and 75-mg/kg/day combination) treatments produced significant reductions in mortality. The wild-type virus infection was markedly reduced in severity by all three combinations (amantadine, 10 mg/kg/day combined with the other compounds at 20 or 40 mg/kg/day) compared to monotherapy with the three compounds. Results indicate a lack of benefit of amantadine in combinations against amantadine-resistant virus, but positive benefits in combinations against amantadine-sensitive virus.

Sign in / Sign up

Export Citation Format

Share Document