scholarly journals ChAdOx1 NiV vaccination protects against lethal Nipah Bangladesh virus infection in African green monkeys

2021 ◽  
Author(s):  
Neeltje van Doremalen ◽  
Victoria Avanzato ◽  
Friederike Feldmann ◽  
Jonathan Schulz ◽  
Elaine Haddock ◽  
...  
Keyword(s):  
Cellular Response ◽  
Nipah Virus ◽  
Post Inoculation ◽  
Lethal Challenge ◽  
Highly Pathogenic ◽  
Challenge Control ◽  
Emerging Virus ◽  
Severe Infections ◽  
Humoral And Cellular Response ◽  
Green Monkeys

Nipah virus (NiV) is a highly pathogenic and re-emerging virus which causes sporadic but severe infections in humans. Currently, no vaccines against NiV have been approved. We previously showed that ChAdOx1 NiV provides full protection against a lethal challenge with NiV Bangladesh (NiV-B) in hamsters. Here, we investigated the efficacy of ChAdOx1 NiV in the lethal African green monkeys (AGMs) NiV challenge model. AGMs were vaccinated either 4 weeks before challenge (prime vaccination), or 8 and 4 weeks before challenge with ChAdOx1 NiV (prime-boost vaccination). A robust humoral and cellular response was detected starting 14 days post initial vaccination. Upon challenge, control animals displayed a variety of signs and had to be euthanized between 5- and 7-days post inoculation. In contrast, vaccinated animals showed no signs of disease, and we were unable to detect infectious virus in all but one swab and all tissues. Importantly, no to limited antibodies against fusion protein or nucleoprotein IgG could be detected 42 days post challenge, suggesting that vaccination induced a very robust protective immune response preventing extensive virus replication.

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 Biological characterisation of the emerged highly pathogenic avian influenza (HPAI) A(H7N9) viruses in humans, in mainland China, 2016 to 2017

2017 ◽  
Vol 22 (19) ◽  
Author(s):  
Wenfei Zhu ◽  
Jianfang Zhou ◽  
Zi Li ◽  
Lei Yang ◽  
Xiyan Li ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Influenza A ◽  
Highly Pathogenic Avian Influenza ◽  
Mainland China ◽  
H7n9 Virus ◽  
Highly Pathogenic ◽  
Pathogenic Avian Influenza ◽  
Binding Preference ◽  
Severe Infections ◽  
Epidemic Wave

With no or low virulence in poultry, avian influenza A(H7N9) virus has caused severe infections in humans. In the current fifth epidemic wave, a highly pathogenic avian influenza (HPAI) H7N9 virus emerged. The insertion of four amino acids (KRTA) at the haemagglutinin (HA) cleavage site enabled trypsin-independent infectivity of this virus. Although maintaining dual receptor-binding preference, its HA antigenicity was distinct from low-pathogenic avian influenza A(H7N9). The neuraminidase substitution R292K conferred a multidrug resistance phenotype.

scholarly journals Mutations in the PA Protein of Avian H5N1 Influenza Viruses Affect Polymerase Activity and Mouse Virulence

2017 ◽  
pp. JVI.01557-17 ◽  
Author(s):  
Gongxun Zhong ◽  
Mai Quynh Le ◽  
Tiago J.S. Lopes ◽  
Peter Halfmann ◽  
Masato Hatta ◽  
...  
Keyword(s):  
Amino Acid ◽  
Case Fatality ◽  
Polymerase Activity ◽  
Influenza Viruses ◽  
Viral Polymerase ◽  
Highly Pathogenic ◽  
H5n1 Influenza ◽  
Increased Risk ◽  
Severe Infections ◽  
Viral Determinants

To study the influenza viral determinants of pathogenicity, we characterized two highly pathogenic avian H5N1 influenza viruses isolated in Vietnam in 2012 (A/duck/Vietnam/QT1480/2012; QT1480) and 2013 (A/duck/Vietnam/QT1728/2013; QT1728) and found that the activity of their polymerase complexes differed significantly, even though both viruses were highly pathogenic in mice. Further studies revealed that the PA-S343A/E347D mutations reduced viral polymerase activity and mouse virulence when tested in the genetic background of QT1728 virus. In contrast, the PA-343S/347E mutations increased the polymerase activity of QT1480 and the virulence of a low pathogenic H5N1 influenza virus. The PA-343S residue (which alone increased viral polymerase activity and mouse virulence significantly relative to viral replication complexes encoding PA-343A) is frequently found in H5N1 influenza viruses of several subclades; infection with a virus possessing this amino acid may pose an increased risk to humans.IMPORTANCEH5N1 influenza viruses cause severe infections in humans with a case fatality rate that exceeds 50%. The factors that determine the high virulence of these viruses in humans are not fully understood. Here, we identified two amino acid changes in the viral polymerase PA protein that affect the activity of the viral polymerase complex and virulence in mice. Infection with viruses possessing these amino acid changes may pose an increased risk to humans.

scholarly journals SARS-CoV-2 mRNA vaccine BNT162b2 triggers a consistent cross-variant humoral and cellular response

2021 ◽  
pp. 1-29
Author(s):  
D Mileto ◽  
C Fenizia ◽  
M Cutrera ◽  
G Gagliardi ◽  
A Gigantiello ◽  
...  
Keyword(s):  
Cellular Response ◽  
Humoral And Cellular Response

scholarly journals Haemagglutinin displayed on the surface of Lactococcus lactis confers broad cross-clade protection against different H5N1 viruses in chickens

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Han Lei ◽  
Tong Gao ◽  
Qianhong Cen ◽  
Xiaojue Peng
Keyword(s):  
Avian Influenza ◽  
Lactococcus Lactis ◽  
Effective Vaccine ◽  
Potential Threat ◽  
Lethal Challenge ◽  
Highly Pathogenic ◽  
Hpai H5n1 ◽  
Ha Protein ◽  
Influenza Virus Haemagglutinin ◽  
Influenza H5n1

Abstract Background The highly pathogenic avian influenza (HPAI) H5N1 virus poses a potential threat to the poultry industry. The currently available avian influenza H5N1 vaccines for poultry are clade-specific. Therefore, an effective vaccine for preventing and controlling H5N1 viruses belonging to different clades needs to be developed. Results Recombinant L. lactis/pNZ8148-Spax-HA was generated, and the influenza virus haemagglutinin (HA) protein of A/Vietnam/1203/2004 (H5N1) was displayed on the surface of Lactococcus lactis (L. lactis). Spax was used as an anchor protein. Chickens vaccinated orally with unadjuvanted L. lactis/pNZ8148-Spax-HA could produce significant humoral and mucosal responses and neutralizing activities against H5N1 viruses belonging to different clades. Importantly, unadjuvanted L. lactis/pNZ8148-Spax-HA conferred cross-clade protection against lethal challenge with different H5N1 viruses in the chicken model. Conclusion This study provides insights into the cross-clade protection conferred by unadjuvanted L. lactis/pNZ8148-Spax-HA, and the results might help the establishment of a promising platform for the development of a safe and effective H5N1 cross-clade vaccine for poultry.

scholarly journals RHΔgra17Δnpt1 Strain of Toxoplasma gondii Elicits Protective Immunity Against Acute, Chronic and Congenital Toxoplasmosis in Mice

2020 ◽  
Vol 8 (3) ◽  
pp. 352 ◽  
Author(s):  
Qin-Li Liang ◽  
Li-Xiu Sun ◽  
Hany M. Elsheikha ◽  
Xue-Zhen Cao ◽  
Lan-Bi Nie ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Cellular Response ◽  
Protective Efficacy ◽  
Interleukin 2 ◽  
Congenital Toxoplasmosis ◽  
Congenital Infection ◽  
Dense Granule ◽  
Lethal Challenge ◽  
Double Deletion ◽  
Brain Cysts

In the present study, a dense granule protein 17 (gra17) and novel putative transporter (npt1) double deletion mutant of Toxoplasma gondii RH strain was engineered. The protective efficacy of vaccination using RHΔgra17Δnpt1 tachyzoites against acute, chronic, and congenital toxoplasmosis was studied in a mouse model. Immunization using RHΔgra17Δnpt1 induced a strong humoral and cellular response, as indicated by the increased levels of anti-T. gondii specific IgG, interleukin 2 (IL-2), IL-10, IL-12, and interferon-gamma (IFN-γ). Vaccinated mice were protected against a lethal challenge dose (103 tachyzoites) of wild-type homologous (RH) strain and heterologous (PYS and TgC7) strains, as well as against 100 tissue cysts or oocysts of Pru strain. Vaccination also conferred protection against chronic infection with 10 tissue cysts or oocysts of Pru strain, where the numbers of brain cysts in the vaccinated mice were significantly reduced compared to those detected in the control (unvaccinated + infected) mice. In addition, vaccination protected against congenital infection with 10 T. gondii Pru oocysts (administered orally on day 5 of gestation) as shown by the increased litter size, survival rate and the bodyweight of pups born to vaccinated dams compared to those born to unvaccinated + infected dams. The brain cyst burden of vaccinated dams was significantly lower than that of unvaccinated dams infected with oocysts. Our data show that T. gondii RHΔgra17Δnpt1 mutant strain can protect mice against acute, chronic, and congenital toxoplasmosis by balancing inflammatory response with immunogenicity.

Long-term patterns of humoral and cellular response after vaccination against influenza A (H1N1) in patients with hematologic malignancies

2012 ◽  
Vol 89 (2) ◽  
pp. 111-119 ◽  
Author(s):  
Jacopo Mariotti ◽  
Francesco Spina ◽  
Cristiana Carniti ◽  
Giovanni Anselmi ◽  
Davide Lucini ◽  
...  
Keyword(s):  
Influenza A ◽  
Cellular Response ◽  
Hematologic Malignancies ◽  
Influenza A H1n1 ◽  
Humoral And Cellular Response

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.

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