scholarly journals Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters

2014 ◽  
Vol 101 ◽  
pp. 26-29 ◽  
Author(s):  
Michael K. Lo ◽  
Brian H. Bird ◽  
Anasuya Chattopadhyay ◽  
Clifton P. Drew ◽  
Brock E. Martin ◽  
...  
Keyword(s):  
Single Dose ◽  
Nipah Virus ◽  
Lethal Challenge ◽  
Syrian Hamsters

scholarly journals Evaluation of a Single-Dose Nucleoside-Modified Messenger RNA Vaccine Encoding Hendra Virus-Soluble Glycoprotein Against Lethal Nipah virus Challenge in Syrian Hamsters

2019 ◽  
Vol 221 (Supplement_4) ◽  
pp. S493-S498 ◽  
Author(s):  
Michael K Lo ◽  
Jessica R Spengler ◽  
Stephen R Welch ◽  
Jessica R Harmon ◽  
JoAnn D Coleman-McCray ◽  
...  
Keyword(s):  
Single Dose ◽  
Immune Responses ◽  
Messenger Rna ◽  
Nipah Virus ◽  
Hendra Virus ◽  
Highly Pathogenic ◽  
Syrian Hamsters ◽  
Virus Challenge ◽  
Pathogenic Viruses ◽  
Rna Vaccine

Abstract In the absence of approved vaccines and therapeutics for use in humans, Nipah virus (NiV) continues to cause fatal outbreaks of encephalitis and respiratory disease in Bangladesh and India on a near-annual basis. We determined that a single dose of a lipid nanoparticle nucleoside-modified messenger RNA vaccine encoding the soluble Hendra virus glycoprotein protected up to 70% of Syrian hamsters from lethal NiV challenge, despite animals having suboptimally primed immune responses before challenge. These data provide a foundation from which to optimize future messenger RNA vaccination studies against NiV and other highly pathogenic viruses.

scholarly journals ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Robert J. Fischer ◽  
Neeltje van Doremalen ◽  
Danielle R. Adney ◽  
Claude Kwe Yinda ◽  
Julia R. Port ◽  
...  
Keyword(s):  
Single Dose ◽  
Vaccine Efficacy ◽  
Infectious Virus ◽  
Neutralizing Antibody ◽  
Subgenomic Rna ◽  
Syrian Hamsters ◽  
Fold Reduction ◽  
Histopathological Evaluation ◽  
Gross Lesions ◽  
Pulmonary Pathology

AbstractWe investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observe a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 do not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals do not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus can be detected in lungs of vaccinated animals. Histopathological evaluation shows extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.

scholarly journals Remdesivir (GS-5734) protects African green monkeys from Nipah virus challenge

2019 ◽  
Vol 11 (494) ◽  
pp. eaau9242 ◽  
Author(s):  
Michael K. Lo ◽  
Friederike Feldmann ◽  
Joy M. Gary ◽  
Robert Jordan ◽  
Roy Bannister ◽  
...  
Keyword(s):  
Virus Disease ◽  
Antiviral Treatment ◽  
Lethal Dose ◽  
Nipah Virus ◽  
Case Fatality ◽  
Emerging Pathogen ◽  
Lethal Challenge ◽  
Once Daily ◽  
Virus Challenge ◽  
Green Monkeys

Nipah virus is an emerging pathogen in the Paramyxoviridae family. Upon transmission of Nipah virus from its natural reservoir, Pteropus spp. fruit bats, to humans, it causes respiratory and neurological disease with a case-fatality rate about 70%. Human-to-human transmission has been observed during Nipah virus outbreaks in Bangladesh and India. A therapeutic treatment for Nipah virus disease is urgently needed. Here, we tested the efficacy of remdesivir (GS-5734), a broad-acting antiviral nucleotide prodrug, against Nipah virus Bangladesh genotype in African green monkeys. Animals were inoculated with a lethal dose of Nipah virus, and a once-daily intravenous remdesivir treatment was initiated 24 hours later and continued for 12 days. Mild respiratory signs were observed in two of four treated animals, whereas all control animals developed severe respiratory disease signs. In contrast to control animals, which all succumbed to the infection, all remsdesivir-treated animals survived the lethal challenge, indicating that remdesivir represents a promising antiviral treatment for Nipah virus infection.

scholarly journals A Single Dose of Modified Vaccinia Ankara Expressing Lassa Virus-like Particles Protects Mice from Lethal Intra-cerebral Virus Challenge

Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 133 ◽  
Author(s):  
Maria S. Salvato ◽  
Arban Domi ◽  
Camila Guzmán-Cardozo ◽  
Sandra Medina-Moreno ◽  
Juan Carlos Zapata ◽  
...  
Keyword(s):  
Single Dose ◽  
Matrix Protein ◽  
Lethal Dose ◽  
Health Impact ◽  
Lassa Virus ◽  
Protein Z ◽  
Glycoprotein Precursor ◽  
Lethal Challenge ◽  
Virus Like Particles ◽  
Virus Challenge

Lassa fever surpasses Ebola, Marburg, and all other hemorrhagic fevers except Dengue in its public health impact. Caused by Lassa virus (LASV), the disease is a scourge on populations in endemic areas of West Africa, where reported incidence is higher. Here, we report construction, characterization, and preclinical efficacy of a novel recombinant vaccine candidate GEO-LM01. Constructed in the Modified Vaccinia Ankara (MVA) vector, GEO-LM01 expresses the glycoprotein precursor (GPC) and zinc-binding matrix protein (Z) from the prototype Josiah strain lineage IV. When expressed together, GP and Z form Virus-Like Particles (VLPs) in cell culture. Immunogenicity and efficacy of GEO-LM01 was tested in a mouse challenge model. A single intramuscular dose of GEO-LM01 protected 100% of CBA/J mice challenged with a lethal dose of ML29, a Mopeia/Lassa reassortant virus, delivered directly into the brain. In contrast, all control animals died within one week. The vaccine induced low levels of antibodies but Lassa-specific CD4+ and CD8+ T cell responses. This is the first report showing that a single dose of a replication-deficient MVA vector can confer full protection against a lethal challenge with ML29 virus.

scholarly journals Peri-exposure protection against Nipah virus disease using a single-dose recombinant vesicular stomatitis virus-based vaccine

npj Vaccines ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Blair L DeBuysscher ◽  
Dana Scott ◽  
Tina Thomas ◽  
Heinz Feldmann ◽  
Joseph Prescott
Keyword(s):  
Single Dose ◽  
Vesicular Stomatitis Virus ◽  
Virus Disease ◽  
Nipah Virus ◽  
Vesicular Stomatitis

scholarly journals Liposome Encapsulation of Ciprofloxacin Improves Protection against Highly Virulent Francisella tularensis Strain Schu S4

2014 ◽  
Vol 58 (6) ◽  
pp. 3053-3059 ◽  
Author(s):  
Karleigh A. Hamblin ◽  
Stuart J. Armstrong ◽  
Kay B. Barnes ◽  
Carwyn Davies ◽  
Jonathan P. Wong ◽  
...  
Keyword(s):  
Single Dose ◽  
Francisella Tularensis ◽  
Infection Model ◽  
Prophylactic Regimen ◽  
Lethal Challenge ◽  
Content Type ◽  
Deliberate Release ◽  
Oral Ciprofloxacin ◽  
Schu S4 ◽  
Full Protection

ABSTRACTLiposome-encapsulated ciprofloxacin for inhalation (CFI) was investigated as a putative postexposure therapeutic for two strains ofFrancisella tularensis. The efficacies of oral ciprofloxacin and intranasally instilled CFI could not be distinguished in a mouse model of infection with theF. tularensislive vaccine strain (LVS), where a single dose of either formulation offered full protection against a lethal challenge. However, mouse studies with the more virulent Schu S4 strain ofF. tularensisdemonstrated that a higher level of protection against a lethal aerosol infection is provided by CFI than by oral ciprofloxacin. In addition, using this infection model, it was possible to discriminate the efficacy of intranasally instilled CFI from that of aerosolized CFI, with aerosolized CFI providing full protection after just a single dose. The improved efficacy of CFI compared to oral ciprofloxacin is likely due to the high sustained concentrations of ciprofloxacin in the lung. In summary, CFI may be a promising therapy, perhaps enabling the prophylactic regimen to be shortened, for use in the event of a deliberate release ofF. tularensis. The prophylactic efficacy of CFI against other biological warfare (BW) threat agents also warrants investigation.

scholarly journals Protective Immunity against Tularemia Provided by an Adenovirus-Vectored Vaccine Expressing Tul4 of Francisella tularensis

2012 ◽  
Vol 19 (3) ◽  
pp. 359-364 ◽  
Author(s):  
Ravinder Kaur ◽  
Shan Chen ◽  
Maria T. Arévalo ◽  
Qingfu Xu ◽  
Yanping Chen ◽  
...  
Keyword(s):  
Single Dose ◽  
Francisella Tularensis ◽  
Virulent Strain ◽  
Lethal Dose ◽  
Protein Vaccine ◽  
Lethal Challenge ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Skin Contact ◽  
Vectored Vaccine

ABSTRACTFrancisella tularensis, a category A bioterrorism agent, is a highly infectious organism that is passed on via skin contact and inhalation routes. A live attenuated vaccine strain (LVS) has been developed, but it has not been licensed for public use by the FDA due to safety concerns. Thus, there exists a need for a safer and improved vaccine. In this study, we have constructed a replication-incompetent adenovirus, Ad/opt-Tul4, carrying a codon-optimized gene for expression of a membrane protein, Tul4, ofF. tularensisLVS. Its ability to protect against lethal challenge and its immunogenicity were evaluated in a murine model. An intramuscular injection of a single dose (1 × 107PFU) of Ad/opt-Tul4 elicited a robust Tul4-specific antibody response. Assays suggest a Th1-driven response. A single dose elicited 20% protection against challenge with 100 × 50% lethal dose (LD50)F. tularensisLVS; two additional booster shots resulted in 60% protection. In comparison, three doses of 5 μg recombinant Tul4 protein did not elicit significant protection against challenge. Therefore, the Ad/opt-Tul4 vaccine was more effective than the protein vaccine, and protection was dose dependent. Compared to LVS, the protection rate is lower, but an adenovirus-vectored vaccine may be more attractive due to its enhanced safety profile and mucosal route of delivery. Furthermore, simple genetic modification of the vaccine may potentially produce antibodies protective against a fully virulent strain ofF. tularensis. Our data support the development and further research of an adenovirus-vectored vaccine against Tul4 ofF. tularensisLVS.

scholarly journals Lung-targeting lentiviral vector for passive immunisation against influenza

Thorax ◽  
2020 ◽  
Vol 75 (12) ◽  
pp. 1112-1115
Author(s):  
Tiong Kit Tan ◽  
Toby P E Gamlen ◽  
Pramila Rijal ◽  
Alain R Townsend ◽  
Deborah R Gill ◽  
...  
Keyword(s):  
Single Dose ◽  
Simian Immunodeficiency Virus ◽  
Transgene Expression ◽  
Lentiviral Vector ◽  
Sendai Virus ◽  
Systemic Circulation ◽  
Passive Immunisation ◽  
Respiratory Pathogens ◽  
Lethal Challenge ◽  
Immunodeficiency Virus

When recombinant simian immunodeficiency virus (SIV) is pseudotyped with the F and HN glycoproteins from murine respiratory Sendai virus (rSIV.F/HN), it provides efficient lung cell targeting and lifelong transgene expression in the murine airways. We have shown that a single dose of rSIV.F/HN can direct stable expression of neutralising antibody against influenza in the murine airways and systemic circulation, and protects mice against two different influenza strains in lethal challenge experiments. These data suggest that rSIV.F/HN could be used as a vector for passive immunisation against influenza and other respiratory pathogens.

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