scholarly journals Live Bivalent Vaccine for Parainfluenza and Influenza Virus Infections

2005 ◽  
Vol 79 (11) ◽  
pp. 6674-6679 ◽  
Author(s):  
Yasuko Maeda ◽  
Masato Hatta ◽  
Ayato Takada ◽  
Tokiko Watanabe ◽  
Hideo Goto ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Reverse Genetics ◽  
Parainfluenza Virus ◽  
Virus Infections ◽  
Coding Region ◽  
Lethal Challenge ◽  
Bivalent Vaccine ◽  
Parainfluenza Viruses ◽  
Human Parainfluenza Virus

ABSTRACT Influenza and human parainfluenza virus infections are of both medical and economical importance. Currently, inactivated vaccines provide suboptimal protection against influenza, and vaccines for human parainfluenza virus infection are not available, underscoring the need for new vaccines against these respiratory diseases. Furthermore, to reduce the burden of vaccination, the development of multivalent vaccines is highly desirable. Thus, to devise a single vaccine that would elicit immune responses against both influenza and parainfluenza viruses, we used reverse genetics to generate an influenza A virus that possesses the coding region for the hemagglutinin/neuraminidase ectodomain of parainfluenza virus instead of the influenza virus neuraminidase. The recombinant virus grew efficiently in eggs but was attenuated in mice. When intranasally immunized with the recombinant vaccine, all mice developed antibodies against both influenza and parainfluenza viruses and survived an otherwise lethal challenge with either of these viruses. This live bivalent vaccine has obvious advantages over combination vaccines, and its method of generation could, in principle, be applied in the development of a “cocktail” vaccine with efficacy against several different infectious diseases.

scholarly journals A Nine-Segment Influenza A Virus Carrying Subtype H1 and H3 Hemagglutinins

2010 ◽  
Vol 84 (16) ◽  
pp. 8062-8071 ◽  
Author(s):  
Qinshan Gao ◽  
Anice C. Lowen ◽  
Taia T. Wang ◽  
Peter Palese
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Fluorescent Protein ◽  
Gene Segment ◽  
Viral Envelope ◽  
Coding Region ◽  
Lethal Challenge ◽  
Genomic Rnas ◽  
Synonymous Mutations ◽  
Packaging Signals

ABSTRACT Influenza virus genomic RNAs possess segment-specific packaging signals that include both noncoding regions (NCRs) and adjacent terminal coding region sequences. Using reverse genetics, an A/Puerto Rico/8/34 (A/PR/8/34) virus was rescued that contained a modified PB1 gene such that the PB1 packaging sequences were exchanged for those of the neuraminidase (NA) gene segment. To accomplish this, the PB1 open reading frame, in which the terminal packaging signals were inactivated by serial synonymous mutations, was flanked by the NA segment-specific packaging sequences including the NCRs and the coding region packaging signals. Next, the ATGs located on the 3′ end of the NA packaging sequences of the resulting PB1 chimeric segment were mutated to allow for correct translation of the full-length PB1 protein. The virus containing this chimeric PB1 segment was viable and able to stably carry a ninth, green fluorescent protein (GFP), segment flanked by PB1 packaging signals. Utilizing this method, we successfully generated an influenza virus that contained the genes coding for both the H1 hemagglutinin (HA) from A/PR/8/34 and the H3 HA from A/Hong Kong/1/68 (A/HK/1/68); both subtypes of HA protein were also incorporated into the viral envelope. Immunization of mice with this recombinant virus conferred complete protection from lethal challenge with recombinant A/PR/8/34 virus and with X31 virus that expresses the A/HK/1/68 HA and NA. Using the described methodology, we show that a ninth segment can also be incorporated by manipulation of the PB2 or PA segment-specific packaging signals. This approach offers a means of generating a bivalent influenza virus vaccine.

scholarly journals Chimeric Hemagglutinin Constructs Induce Broad Protection against Influenza B Virus Challenge in the Mouse Model

2017 ◽  
Vol 91 (12) ◽  
Author(s):  
Megan E. Ermler ◽  
Ericka Kirkpatrick ◽  
Weina Sun ◽  
Rong Hai ◽  
Fatima Amanat ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Antiviral Drug ◽  
Antigenic Drift ◽  
Influenza B Virus ◽  
Influenza B ◽  
Virus Infections ◽  
Lethal Challenge ◽  
Public Health Burden ◽  
B Virus

ABSTRACT Seasonal influenza virus epidemics represent a significant public health burden. Approximately 25% of all influenza virus infections are caused by type B viruses, and these infections can be severe, especially in children. Current influenza virus vaccines are an effective prophylaxis against infection but are impacted by rapid antigenic drift, which can lead to mismatches between vaccine strains and circulating strains. Here, we describe a broadly protective vaccine candidate based on chimeric hemagglutinins, consisting of globular head domains from exotic influenza A viruses and stalk domains from influenza B viruses. Sequential vaccination with these constructs in mice leads to the induction of broadly reactive antibodies that bind to the conserved stalk domain of influenza B virus hemagglutinin. Vaccinated mice are protected from lethal challenge with diverse influenza B viruses. Results from serum transfer experiments and antibody-dependent cell-mediated cytotoxicity (ADCC) assays indicate that this protection is antibody mediated and based on Fc effector functions. The present data suggest that chimeric hemagglutinin-based vaccination is a viable strategy to broadly protect against influenza B virus infection. IMPORTANCE While current influenza virus vaccines are effective, they are affected by mismatches between vaccine strains and circulating strains. Furthermore, the antiviral drug oseltamivir is less effective for treating influenza B virus infections than for treating influenza A virus infections. A vaccine that induces broad and long-lasting protection against influenza B viruses is therefore urgently needed.

A replication-incompetent influenza virus bearing the HN glycoprotein of human parainfluenza virus as a bivalent vaccine

Vaccine ◽  
2013 ◽  
Vol 31 (52) ◽  
pp. 6239-6246 ◽  
Author(s):  
Hirofumi Kobayashi ◽  
Kiyoko Iwatsuki-Horimoto ◽  
Maki Kiso ◽  
Ryuta Uraki ◽  
Yurie Ichiko ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Parainfluenza Virus ◽  
Bivalent Vaccine ◽  
Human Parainfluenza Virus

scholarly journals Influenza Virus Protecting RNA: an Effective Prophylactic and Therapeutic Antiviral

2008 ◽  
Vol 82 (17) ◽  
pp. 8570-8578 ◽  
Author(s):  
Nigel J. Dimmock ◽  
Edward W. Rainsford ◽  
Paul D. Scott ◽  
Anthony C. Marriott
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Influenza Pandemic ◽  
Therapeutic Benefit ◽  
Virus Infections ◽  
Influenza A Viruses ◽  
Lethal Challenge ◽  
Human Influenza Virus ◽  
Challenge Virus ◽  
Virus Rna

ABSTRACT Another influenza pandemic is inevitable, and new measures to combat this and seasonal influenza are urgently needed. Here we describe a new concept in antivirals based on a defined, naturally occurring defective influenza virus RNA that has the potential to protect against any influenza A virus in any animal host. This “protecting RNA” (244 RNA) is incorporated into virions which, although noninfectious, deliver the RNA to those cells of the respiratory tract that are naturally targeted by infectious influenza virus. A 120-ng intranasal dose of this 244 protecting virus completely protected mice against a simultaneous challenge of 10 50% lethal doses with influenza A/WSN (H1N1) virus. The 244 virus also protected mice against strong challenge doses of all other subtypes tested (i.e., H2N2, H3N2, and H3N8). This prophylactic activity was maintained in the animal for at least 1 week prior to challenge. The 244 virus was 10- to 100-fold more active than previously characterized defective influenza A viruses, and the protecting activity was confirmed to reside in the 244 RNA molecule by recovering a protecting virus entirely from cloned cDNA. There was a clear therapeutic benefit when the 244 virus was administered 24 to 48 h after a lethal challenge, an effect which has not been previously observed with any defective virus. Protecting virus reduced, but did not abolish, replication of challenge virus in mouse lungs during both prophylactic and therapeutic treatments. Protecting virus is a novel antiviral, having the potential to combat human influenza virus infections, particularly when the infecting strain is not known or is resistant to antiviral drugs.

scholarly journals Surveillance of respiratory viral infections by rapid immunofluorescence diagnosis, with emphasis on virus interference

1987 ◽  
Vol 99 (2) ◽  
pp. 523-531 ◽  
Author(s):  
G. Ånestad
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Relative Increase ◽  
Parainfluenza Virus ◽  
Epidemic Curve ◽  
Parainfluenza Viruses ◽  
If Technique ◽  
Sporadic Cases ◽  
Syncytial Virus

SUMMARYDuring the 7-year period from September 1978 to August 1985, smear specimens of nasopharyngeal secretions from 3132 patients mainly hospitalized children, taken in different regions in Norway, were examined for respiratory viruses by the rapid immunofluorescence (IF) technique. A positive diagnosis for respiratory syncytial virus (RSV), parainfluenza virus type 1, 2 and 3 or influenza A and B virus was made for 896 patients (29%). The greatest prevalence for all these viruses was observed during the colder months with only sporadic cases during the summer months. A relative increase in parainfluenza virus activity, involving several parainfluenza virus types, was observed in every second autumn and during these periods only sporadic cases of RSV infection were diagnosed. Also both RSV and parainfluenza viruses were less frequently found during influenza virus epidemics and regional differences in RSV activity were observed. During the four autumn periods 1982–85 the monthly number of positive virus identifications by IF followed an epidemic curve, while the corresponding number of negative samples was relatively constant. The results of this study suggest interference between RSV, parainfluenza viruses and influenza virus in reaching their epidemiological peaks. It is suggested that interferon might be a mediator of this effect.

scholarly journals Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James D. Allen ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Virus Infections ◽  
Wild Type ◽  
Influenza Hemagglutinin ◽  
H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

scholarly journals Exacerbation of Influenza Virus Infections in Mice by Intranasal Treatments and Implications for Evaluation of Antiviral Drugs

2012 ◽  
Vol 56 (12) ◽  
pp. 6328-6333 ◽  
Author(s):  
Donald F. Smee ◽  
Mark von Itzstein ◽  
Beenu Bhatt ◽  
E. Bart Tarbet
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
H1n1 Virus ◽  
Antiviral Agent ◽  
Virus Production ◽  
Lung Pathology ◽  
Virus Infections ◽  
Challenge Dose ◽  
Virus Challenge ◽  
Time To Death

ABSTRACTCompounds lacking oral activity may be delivered intranasally to treat influenza virus infections in mice. However, intranasal treatments greatly enhance the virulence of such virus infections. This can be partially compensated for by giving reduced virus challenge doses. These can be 100- to 1,000-fold lower than infections without such treatment and still cause equivalent mortality. We found that intranasal liquid treatments facilitate virus production (probably through enhanced virus spread) and that lung pneumonia was delayed by only 2 days relative to a 1,000-fold higher virus challenge dose not accompanied by intranasal treatments. In one study, zanamivir was 90 to 100% effective at 10 mg/kg/day by oral, intraperitoneal, and intramuscular routes against influenza A/California/04/2009 (H1N1) virus in mice. However, the same compound administered intranasally at 20 mg/kg/day for 5 days gave no protection from death although the time to death was significantly delayed. A related compound, Neu5Ac2en (N-acetyl-2,3-dehydro-2-deoxyneuraminic acid), was ineffective at 100 mg/kg/day. Intranasal zanamivir and Neu5Ac2en were 70 to 100% protective against influenza A/NWS/33 (H1N1) virus infections at 0.1 to 10 and 30 to 100 mg/kg/day, respectively. Somewhat more difficult to treat was A/Victoria/3/75 virus that required 10 mg/kg/day of zanamivir to achieve full protection. These results illustrate that treatment of influenza virus infections by the intranasal route requires consideration of both virus challenge dose and virus strain in order to avoid compromising the effectiveness of a potentially useful antiviral agent. In addition, the intranasal treatments were shown to facilitate virus replication and promote lung pathology.

scholarly journals In Vivo Influenza Virus-Inhibitory Effects of the Cyclopentane Neuraminidase Inhibitor RWJ-270201

2001 ◽  
Vol 45 (3) ◽  
pp. 749-757 ◽  
Author(s):  
Robert W. Sidwell ◽  
Donald F. Smee ◽  
John H. Huffman ◽  
Dale L. Barnard ◽  
Kevin W. Bailey ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Hong Kong ◽  
Influenza A ◽  
Arterial Oxygen Saturation ◽  
Virus Titer ◽  
Neuraminidase Inhibitor ◽  
Arterial Oxygen ◽  
Virus Infections ◽  
Inhibitory Effects ◽  
Lung Consolidation

ABSTRACT The cyclopentane influenza virus neuraminidase inhibitor RWJ-270201 was evaluated against influenza A/NWS/33 (H1N1), A/Shangdong/09/93 (H3N2), A/Victoria/3/75 (H3N2), and B/Hong Kong/05/72 virus infections in mice. Treatment was by oral gavage twice daily for 5 days beginning 4 h pre-virus exposure. The influenza virus inhibitor oseltamivir was run in parallel, and ribavirin was included in studies with the A/Shangdong and B/Hong Kong viruses. RWJ-270201 was inhibitory to all infections using doses as low as 1 mg/kg/day. Oseltamivir was generally up to 10-fold less effective than RWJ-270201. Ribavirin was also inhibitory but was less tolerated by the mice at the 75-mg/kg/day dose used. Disease-inhibitory effects included prevention of death, lessening of decline of arterial oxygen saturation, inhibition of lung consolidation, and reduction in lung virus titers. RWJ-270201 and oseltamivir, at doses of 10 and 1 mg/kg/day each, were compared with regard to their effects on daily lung parameters in influenza A/Shangdong/09/93 virus-infected mice. Maximum virus titer inhibition was seen on day 1, with RWJ-270201 exhibiting the greater inhibitory effect, a titer reduction of >104 cell culture 50% infective doses (CCID50)/g. By day 8, the lung virus titers in mice treated with RWJ-270201 had declined to 101.2 CCID50/g, whereas titers from oseltamivir-treated animals were >103CCID50/g. Mean lung consolidation was also higher in the oseltamivir-treated animals on day 8. Both neuraminidase inhibitors were well tolerated by the mice. RWJ-270201 was nontoxic at doses as high as 1,000 mg/kg/day. These data indicate potential for the oral use of RWJ-270201 in the treatment of influenza virus infections in humans.

scholarly journals Curcumin Inhibits Replication of Human Parainfluenza Virus Type 3 by Affecting Viral Inclusion Body Formation

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Chaoliang Zhang ◽  
Kehan Zhang ◽  
Guangchao Zang ◽  
Tingting Chen ◽  
Nan Lu ◽  
...  
Keyword(s):  
Inclusion Body ◽  
Virus Type ◽  
Antiviral Drug ◽  
Parainfluenza Virus ◽  
Parainfluenza Viruses ◽  
Inclusion Body Formation ◽  
Viral Inclusion ◽  
Tract Infections ◽  
Human Parainfluenza Virus ◽  
Type 3

Human Parainfluenza Virus Type 3 (HPIV3) is one of the main pathogens that cause acute lower respiratory tract infections in infants and young children. However, there are currently no effective antiviral drugs and vaccines. Herein, we found that a natural compound, curcumin, inhibits HPIV3 infection and has antiviral effects on entry and replication of the virus life cycle. Immunofluorescence and western blotting experiments revealed that curcumin disrupts F-actin and inhibits viral inclusion body (IB) formation, thus inhibiting virus replication. Curcumin can also downregulate cellular PI4KB and interrupt its colocalization in viral IBs. This study verified the antiviral ability of curcumin on HPIV3 infection and preliminarily elucidated its influence on viral replication, providing a theoretical basis for antiviral drug development of HPIV3 and other parainfluenza viruses.

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