scholarly journals Dendrimer-RNA nanoparticles generate protective immunity against lethal Ebola, H1N1 influenza, and Toxoplasma gondii challenges with a single dose

2016 ◽  
Vol 113 (29) ◽  
pp. E4133-E4142 ◽  
Author(s):  
Jasdave S. Chahal ◽  
Omar F. Khan ◽  
Christopher L. Cooper ◽  
Justine S. McPartlan ◽  
Jonathan K. Tsosie ◽  
...  
Keyword(s):  
Single Dose ◽  
Toxoplasma Gondii ◽  
Protective Immunity ◽  
Ebola Virus ◽  
H1n1 Influenza ◽  
Antibody Responses ◽  
Emerging Pathogens ◽  
Vaccine Platform ◽  
Production Methods ◽  
Multiple Antigen

Vaccines have had broad medical impact, but existing vaccine technologies and production methods are limited in their ability to respond rapidly to evolving and emerging pathogens, or sudden outbreaks. Here, we develop a rapid-response, fully synthetic, single-dose, adjuvant-free dendrimer nanoparticle vaccine platform wherein antigens are encoded by encapsulated mRNA replicons. To our knowledge, this system is the first capable of generating protective immunity against a broad spectrum of lethal pathogen challenges, including H1N1 influenza, Toxoplasma gondii, and Ebola virus. The vaccine can be formed with multiple antigen-expressing replicons, and is capable of eliciting both CD8+ T-cell and antibody responses. The ability to generate viable, contaminant-free vaccines within days, to single or multiple antigens, may have broad utility for a range of diseases.

scholarly journals Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations

Pharmaceutics ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 989
Author(s):  
Hae-Ji Kang ◽  
Ki-Back Chu ◽  
Min-Ju Kim ◽  
Hyunwoo Park ◽  
Hui Jin ◽  
...  
Keyword(s):  
B Cells ◽  
Toxoplasma Gondii ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Antibody Responses ◽  
Strongly Correlated ◽  
Cpg Odn ◽  
Virus Like Particle ◽  
Iga Antibody ◽  
Specific Igg

Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4+ and CD8+ T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines.

scholarly journals Vesicular Stomatitis Virus Pseudotyped with Ebola Virus Glycoprotein Serves as a Protective, Noninfectious Vaccine against Ebola Virus Challenge in Mice

2017 ◽  
Vol 91 (17) ◽  
Author(s):  
Nicholas J. Lennemann ◽  
Andrew S. Herbert ◽  
Rachel Brouillette ◽  
Bethany Rhein ◽  
Russell A. Bakken ◽  
...  
Keyword(s):  
Single Dose ◽  
West Africa ◽  
Vesicular Stomatitis Virus ◽  
Ebola Virus ◽  
Dependent Manner ◽  
Wild Type ◽  
Vaccine Platform ◽  
Virus Glycoprotein ◽  
Conserved Regions ◽  
Vesicular Stomatitis

ABSTRACT The recent Ebola virus (EBOV) epidemic in West Africa demonstrates the potential for a significant public health burden caused by filoviral infections. No vaccine or antiviral is currently FDA approved. To expand the vaccine options potentially available, we assessed protection conferred by an EBOV vaccine composed of vesicular stomatitis virus pseudovirions that lack native G glycoprotein (VSVΔG) and bear EBOV glycoprotein (GP). These pseudovirions mediate a single round of infection. Both single-dose and prime/boost vaccination regimens protected mice against lethal challenge with mouse-adapted Ebola virus (ma-EBOV) in a dose-dependent manner. The prime/boost regimen provided significantly better protection than a single dose. As N-linked glycans are thought to shield conserved regions of the EBOV GP receptor-binding domain (RBD), thereby blocking epitopes within the RBD, we also tested whether VSVΔG bearing EBOV GPs that lack GP1 N-linked glycans provided effective immunity against challenge with ma-EBOV or a more distantly related virus, Sudan virus. Using a prime/boost strategy, high doses of GP/VSVΔG partially or fully denuded of N-linked glycans on GP1 protected mice against ma-EBOV challenge, but these mutants were no more effective than wild-type (WT) GP/VSVΔG and did not provide cross protection against Sudan virus. As reported for other EBOV vaccine platforms, the protection conferred correlated with the quantity of EBOV GP-specific Ig produced but not with the production of neutralizing antibodies. Our results show that EBOV GP/VSVΔG pseudovirions serve as a successful vaccination platform in a rodent model of Ebola virus disease and that GP1 N-glycan loss does not influence immunogenicity or vaccination success. IMPORTANCE The West African Ebola virus epidemic was the largest to date, with more than 28,000 people infected. No FDA-approved vaccines are yet available, but in a trial vaccination strategy in West Africa, recombinant, infectious VSV encoding the Ebola virus glycoprotein effectively prevented virus-associated disease. VSVΔG pseudovirion vaccines may prove as efficacious and have better safety, but they have not been tested to date. Thus, we tested the efficacy of VSVΔG pseudovirions bearing Ebola virus glycoprotein as a vaccine platform. We found that wild-type Ebola virus glycoprotein, in the context of this platform, provides robust protection of EBOV-challenged mice. Further, we found that removal of the heavy glycan shield surrounding conserved regions of the glycoprotein does not enhance vaccine efficacy.

scholarly journals Immunogenicity of an AAV-based, room-temperature stable, single dose COVID-19 vaccine in mice and non-human primates

2021 ◽  
Author(s):  
Nerea Zabaleta ◽  
Wenlong Dai ◽  
Urja Bhatt ◽  
Jessica A Chichester ◽  
Reynette Estelien ◽  
...  
Keyword(s):  
Single Dose ◽  
Room Temperature ◽  
Neutralizing Antibody ◽  
Global Scale ◽  
Emerging Pathogens ◽  
Vaccine Platform ◽  
Population Immunity ◽  
Antibody Titers ◽  
High Yields ◽  
Effective Immunization

SummaryThe SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 million deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological and logistical attributes of the vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity in mouse and nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained at 5 months and are complemented by functional memory T-cells responses. The AAVrh32.33 capsid of the AAVCOVID vaccine is an engineered AAV to which no relevant pre-existing immunity exists in humans. Moreover, the vaccine is stable at room temperature for at least one month and is produced at high yields using established commercial manufacturing processes in the gene therapy industry. Thus, this methodology holds as a very promising single dose, thermostable vaccine platform well-suited to address emerging pathogens on a global scale.

scholarly journals Rapid Protection from COVID-19 in Nonhuman Primates Vaccinated Intramuscularly but Not Intranasally with a Single Dose of a Vesicular Stomatitis Virus-Based Vaccine

mBio ◽  
2022 ◽  
Author(s):  
Wakako Furuyama ◽  
Kyle Shifflett ◽  
Amanda N. Pinski ◽  
Amanda J. Griffin ◽  
Friederike Feldmann ◽  
...  
Keyword(s):  
Single Dose ◽  
Vesicular Stomatitis Virus ◽  
Nonhuman Primates ◽  
Ebola Virus ◽  
European Medicines Agency ◽  
Vaccine Platform ◽  
Vesicular Stomatitis ◽  
Deadly Disease ◽  
Human Use ◽  
The U.S

The vesicular stomatitis virus (VSV) vaccine platform rose to fame in 2019, when a VSV-based Ebola virus (EBOV) vaccine was approved by the European Medicines Agency and the U.S. Food and Drug Administration for human use against the deadly disease.

Biological Hazards

2017 ◽  
Author(s):  
Mark Russi
Keyword(s):  
Ebola Virus ◽  
Virus Disease ◽  
Middle Eastern ◽  
H1n1 Influenza ◽  
Emerging Infections ◽  
Bloodborne Pathogens ◽  
Oral Transmission ◽  
B Virus ◽  
Animal Contact ◽  
Novel H1n1 Influenza

This chapter describes various biological hazards and their impact on workers and others. A major focus of the chapter is biological hazards in healthcare and laboratory settings, including exposure to bloodborne pathogens and prevention of diseases related to them. Sections deal with sharps injuries, HIV/AIDS, hepatitis B virus, hepatitis C virus, tuberculosis, and other infectious diseases that can be acquired in the work environment via direct contact, droplet or airborne spread, or fecal-oral transmission. In addition, infectious agents spread by animal contact or arthropod vectors in a broad range of settings will be addressed. Newly emerging infectious or re-emerging infections, such as those due to H5N1 and novel H1N1 influenza, Middle Eastern respiratory syndrome (MERS), and Ebola Virus Disease (EVD) as well as agents associated with bioterrorism are discussed.

scholarly journals Antibody-Dependent Enhancement of Ebola Virus Infection

2003 ◽  
Vol 77 (13) ◽  
pp. 7539-7544 ◽  
Author(s):  
Ayato Takada ◽  
Heinz Feldmann ◽  
Thomas G. Ksiazek ◽  
Yoshihiro Kawaoka
Keyword(s):  
Virus Infection ◽  
Ebola Virus ◽  
Human Populations ◽  
Hemorrhagic Disease ◽  
Viral Infectivity ◽  
Kidney Cells ◽  
Emerging Pathogens ◽  
Viral Glycoprotein ◽  
Antibody Dependent Enhancement ◽  
Ebola Virus Infection

ABSTRACT Most strains of Ebola virus cause a rapidly fatal hemorrhagic disease in humans, yet there are still no biologic explanations that adequately account for the extreme virulence of these emerging pathogens. Here we show that Ebola Zaire virus infection in humans induces antibodies that enhance viral infectivity. Plasma or serum from convalescing patients enhanced the infection of primate kidney cells by the Zaire virus, and this enhancement was mediated by antibodies to the viral glycoprotein and by complement component C1q. Our results suggest a novel mechanism of antibody-dependent enhancement of Ebola virus infection, one that would account for the dire outcome of Ebola outbreaks in human populations.

scholarly journals The influence and enlightenment of five public health emergencies on public psychology since new century: A systematic review

2021 ◽  
pp. 002076402110022
Author(s):  
Zhifeng Wang ◽  
Dongmei Wang
Keyword(s):  
Public Health ◽  
Ebola Virus ◽  
Psychological Intervention ◽  
Virus Disease ◽  
H1n1 Influenza ◽  
Psychological State ◽  
Wild Animals ◽  
Post Traumatic Stress ◽  
Public Health Emergencies ◽  
The People

Background: Since the 21st century, humans have experienced five public health emergencies: the severe acute respiratory syndrome (SARS), type A H1N1 influenza (H1N1), Middle East respiratory syndrome (MERS), Ebola virus disease (EVD), and the new coronavirus pneumonia (COVID-19). They caused a large number of casualties and a wider psychological crisis, which might cause severe consequences such as post-traumatic stress disorder and suicide. Aims: To reveal the law of formation of public psychological crisis in public health emergencies, and draw lessons from it. To provide ideas for effectively deal with these psychological crisis problems and fundamentally curbing the occurrence of public health emergencies. Method: Through the method of literature research, ‘public health incidents’, ‘psychological crisis’, ‘mental health’, ‘psychological intervention’, ‘SARS’, ‘H1N1’, ‘MERS’, ‘EVD’, and ‘COVID-19’ were used to search literatures in the databases such as PubMed, Springer, and Sciencedirect, and the literatures were summarized, sorted, and studied. Results: (1) The public health emergencies caused a universal psychological crisis. The main manifestations were depression, compulsion, despair, etc. The people involved mainly include patients, suspected isolated patients, medical staff, and the general public in the epidemic situation. (2) People’s psychological state often experienced stress stage, shock stage, acceptance, and reorganization. Only some susceptible individuals couldn’t complete effective psychological reconstruction, resulting in serious psychological disorders. Individual susceptibility is related to genetic factors, adversity, and traumatic stimuli experienced in early life. Conclusion: To reduce these psychological crisis problems, we should establish and improve the psychological crisis intervention or rescue system of public health emergencies, it was still necessary to live in harmony with nature, get rid of the inappropriate habit of preying on wild animals, in order to prevent the cross-species transmission of the virus between wild animals and humans, and to fundamentally avoid the occurrence of major infectious diseases.

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