scholarly journals Immune Serum Produced by DNA Vaccination Protects Hamsters against Lethal Respiratory Challenge with Andes Virus

2007 ◽  
Vol 82 (3) ◽  
pp. 1332-1338 ◽  
Author(s):  
Jay W. Hooper ◽  
Anthony M. Ferro ◽  
Victoria Wahl-Jensen
Keyword(s):  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Lethal Dose ◽  
Case Fatality ◽  
Immune Serum ◽  
Human Infection ◽  
M Gene ◽  
Hamster Model ◽  
Highly Pathogenic ◽  
Andes Virus

ABSTRACT Hantavirus pulmonary syndrome (HPS) is a highly pathogenic disease (40% case fatality rate) carried by rodents chronically infected with certain viruses within the genus Hantavirus of the family Bunyaviridae. The primary mode of transmission to humans is thought to be inhalation of excreta from infected rodents; however, ingestion of contaminated material and rodent bites are also possible modes of transmission. Person-to-person transmission of HPS caused by one species of hantavirus, Andes virus (ANDV), has been reported. Previously, we reported that ANDV injected intramuscularly causes a disease in Syrian hamsters that closely resembles HPS in humans. Here we tested whether ANDV was lethal in hamsters when it was administered by routes that more accurately model the most common routes of human infection, i.e., the subcutaneous, intranasal, and intragastric routes. We discovered that ANDV was lethal by all three routes. Remarkably, even at very low doses, ANDV was highly pathogenic when it was introduced by the mucosal routes (50% lethal dose [LD50], ∼100 PFU). We performed passive transfer experiments to test the capacity of neutralizing antibodies to protect against lethal intranasal challenge. The neutralizing antibodies used in these experiments were produced in rabbits vaccinated by electroporation with a previously described ANDV M gene-based DNA vaccine, pWRG/AND-M. Hamsters that were administered immune serum on days −1 and +5 relative to challenge were protected against intranasal challenge (21 LD50). These findings demonstrate the utility of using the ANDV hamster model to study transmission across mucosal barriers and provide evidence that neutralizing antibodies produced by DNA vaccine technology can be used to protect against challenge by the respiratory route.

scholarly journals Construction and Nonclinical Testing of a Puumala Virus Synthetic M Gene-Based DNA Vaccine

2012 ◽  
Vol 20 (2) ◽  
pp. 218-226 ◽  
Author(s):  
R. L. Brocato ◽  
M. J. Josleyn ◽  
V. Wahl-Jensen ◽  
C. S. Schmaljohn ◽  
J. W. Hooper
Keyword(s):  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Disease Model ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Puumala Virus ◽  
M Gene ◽  
Reading Frame ◽  
Andes Virus

ABSTRACTPuumala virus (PUUV) is a causative agent of hemorrhagic fever with renal syndrome (HFRS). Although PUUV-associated HFRS does not result in high case-fatality rates, the social and economic impact is considerable. There is no licensed vaccine or specific therapeutic to prevent or treat HFRS. Here we report the synthesis of a codon-optimized, full-length M segment open reading frame and its cloning into a DNA vaccine vector to produce the plasmid pWRG/PUU-M(s2). pWRG/PUU-M(s2) delivered by gene gun produced high-titer neutralizing antibodies in hamsters and nonhuman primates. Vaccination with pWRG/PUU-M(s2) protected hamsters against infection with PUUV but not against infection by related HFRS-associated hantaviruses. Unexpectedly, vaccination protected hamsters in a lethal disease model of Andes virus (ANDV) in the absence of ANDV cross-neutralizing antibodies. This is the first evidence that an experimental DNA vaccine for HFRS can provide protection in a hantavirus lethal disease model.

scholarly journals Comparing New-Generation Candidate Vaccines against Human Orthopoxvirus Infections

Acta Naturae ◽  
2017 ◽  
Vol 9 (2) ◽  
pp. 88-93 ◽  
Author(s):  
R. A. Maksyutov ◽  
S. N. Yakubitskyi ◽  
I. V. Kolosova ◽  
S. N. Shchelkunov
Keyword(s):  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Lethal Dose ◽  
Variola Virus ◽  
Highly Pathogenic ◽  
Targeted Deletion ◽  
Vaccination Strategies ◽  
Increased Risk ◽  
Bioterrorism Agent ◽  
New Generation

The lack of immunity to the variola virus in the population, increasingly more frequent cases of human orthopoxvirus infection, and increased risk of the use of the variola virus (VARV) as a bioterrorism agent call for the development of modern, safe vaccines against orthopoxvirus infections. We previously developed a polyvalent DNA vaccine based on five VARV antigens and an attenuated variant of the vaccinia virus (VACV) with targeted deletion of six genes (VAC6). Independent experiments demonstrated that triple immunization with a DNA vaccine and double immunization with VAC6 provide protection to mice against a lethal dose (10 LD50) of the ectromelia virus (ECTV), which is highly pathogenic for mice. The present work was aimed at comparing the immunity to smallpox generated by various immunization protocols using the DNA vaccine and VAC6. It has been established that immunization of mice with a polyvalent DNA vaccine, followed by boosting with recombinant VAC6, as well as double immunization with VAC6, induces production of VACV-neutralizing antibodies and provides protection to mice against a 150 LD50 dose of ECTV. The proposed immunization protocols can be used to develop safe vaccination strategies against smallpox and other human orthopoxvirus infections.

scholarly journals DNA Vaccination with the Hantaan Virus M Gene Protects Hamsters against Three of Four HFRS Hantaviruses and Elicits a High-Titer Neutralizing Antibody Response in Rhesus Monkeys

2001 ◽  
Vol 75 (18) ◽  
pp. 8469-8477 ◽  
Author(s):  
J. W. Hooper ◽  
D. M. Custer ◽  
E. Thompson ◽  
C. S. Schmaljohn
Keyword(s):  
Antibody Response ◽  
Rhesus Monkeys ◽  
Neutralizing Antibodies ◽  
Dna Vaccines ◽  
Surrogate Marker ◽  
Case Fatality ◽  
Neutralizing Antibody ◽  
Dna Vaccination ◽  
Hantaan Virus ◽  
M Gene

ABSTRACT Four hantaviruses—Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus—are known to cause hemorrhagic fever with renal syndrome (HFRS) in Europe and Asia. HTNV causes the most severe form of HFRS (5 to 15% case-fatality rate) and afflicts tens of thousands of people annually. Previously, we demonstrated that DNA vaccination with a plasmid expressing the SEOV M gene elicited neutralizing antibodies and protected hamsters against infection with SEOV and HTNV. Here, we report the construction and evaluation of a DNA vaccine that expresses the HTNV M gene products, G1 and G2. DNA vaccination of hamsters with the HTNV M gene conferred sterile protection against infection with HTNV, SEOV, and DOBV. DNA vaccination of rhesus monkeys with either the SEOV or HTNV M gene elicited high levels of neutralizing antibodies. These are the first immunogenicity data for hantavirus DNA vaccines in nonhuman primates. Because a neutralizing antibody response is considered a surrogate marker for protective immunity in humans, our protection data in hamsters combined with the immunogenicity data in monkeys suggest that hantavirus M gene-based DNA vaccines could protect humans against the most severe forms of HFRS.

scholarly journals Active and Passive Vaccination against Hantavirus Pulmonary Syndrome with Andes Virus M Genome Segment-Based DNA Vaccine

2003 ◽  
Vol 77 (18) ◽  
pp. 9894-9905 ◽  
Author(s):  
D. M. Custer ◽  
E. Thompson ◽  
C. S. Schmaljohn ◽  
T. G. Ksiazek ◽  
J. W. Hooper
Keyword(s):  
Neutralizing Antibodies ◽  
Rhesus Macaques ◽  
Case Fatality ◽  
Viral Disease ◽  
Genome Segment ◽  
Hantavirus Pulmonary Syndrome ◽  
South American ◽  
Andes Virus ◽  
Passive Vaccination ◽  
M Genome

ABSTRACT Hantavirus pulmonary syndrome (HPS) is a rapidly progressing human disease with one of the highest case fatality rates (30 to 50%) of any acute viral disease known. There are no vaccines, effective antiviral drugs, or immunologics to prevent or treat HPS. In an attempt to develop HPS medical countermeasures, we constructed an expression plasmid, pWRG/AND-M, that contains the full-length M genome segment of Andes virus (ANDV), a South American hantavirus. Transfection experiments in cell culture indicated that both the G1 and G2 glycoproteins are expressed from pWRG/AND-M. Rhesus macaques vaccinated by gene gun with pWRG/AND-M developed remarkably high levels of neutralizing antibodies that not only neutralized ANDV but also cross-neutralized other HPS-associated hantaviruses, including Sin Nombre virus. To determine if the antibodies elicited in the monkeys could confer protection, we performed a series of passive-transfer experiments using a recently described lethal HPS animal model (i.e., adult Syrian hamsters develop HPS and die within 10 to 15 days after challenge with ANDV). When injected into hamsters 1 day before challenge, sera from the vaccinated monkeys either provided sterile protection or delayed the onset of HPS and death. When injected on day 4 or 5 after challenge, the monkey sera protected 100% of the hamsters from lethal disease. These data provide a proof of concept for a gene-based HPS vaccine and also demonstrate the potential value of a postexposure immunoprophylactic to treat individuals after exposure, or potential exposure, to these highly lethal hantaviruses.

scholarly journals DNA Based Vaccine Expressing SARS-CoV-2 Spike-CD40L Fusion Protein Confers Protection Against Challenge in a Syrian Hamster Model

2022 ◽  
Vol 12 ◽  
Author(s):  
Levi A. Tamming ◽  
Diana Duque ◽  
Anh Tran ◽  
Wanyue Zhang ◽  
Annabelle Pfeifle ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Effective Means ◽  
Cd40 Ligand ◽  
Storage Conditions ◽  
Lung Pathology ◽  
Hamster Model ◽  
Molecular Adjuvant ◽  
Single Intramuscular Injection

SARS-CoV-2 infections present a tremendous threat to public health. Safe and efficacious vaccines are the most effective means in preventing the infections. A variety of vaccines have demonstrated excellent efficacy and safety around the globe. Yet, development of alternative forms of vaccines remains beneficial, particularly those with simpler production processes, less stringent storage conditions, and the capability of being used in heterologous prime/boost regimens which have shown improved efficacy against many diseases. Here we reported a novel DNA vaccine comprised of the SARS-CoV-2 spike protein fused with CD40 ligand (CD40L) serving as both a targeting ligand and molecular adjuvant. A single intramuscular injection in Syrian hamsters induced significant neutralizing antibodies 3-weeks after vaccination, with a boost substantially improving immune responses. Moreover, the vaccine also reduced weight loss and suppressed viral replication in the lungs and nasal turbinates of challenged animals. Finally, the incorporation of CD40L into the DNA vaccine was shown to reduce lung pathology more effectively than the DNA vaccine devoid of CD40L. These results collectively indicate that this DNA vaccine candidate could be further explored because of its efficacy and known safety profile.

scholarly journals Neutralizing Monoclonal Antibodies against the Gn and the Gc of the Andes Virus Glycoprotein Spike Complex Protect from Virus Challenge in a Preclinical Hamster Model

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
James Duehr ◽  
Meagan McMahon ◽  
Brandi Williamson ◽  
Fatima Amanat ◽  
Alan Durbin ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Treatment Options ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Escape Mutant ◽  
Hamster Model ◽  
Virus Challenge ◽  
Glycoprotein Complex ◽  
The Andes ◽  
Andes Virus

ABSTRACT Hantaviruses are the etiological agent of hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). The latter is associated with case fatality rates ranging from 30% to 50%. HCPS cases are rare, with approximately 300 recorded annually in the Americas. Recently, an HCPS outbreak of unprecedented size has been occurring in and around Epuyén, in the southwestern Argentinian state of Chubut. Since November of 2018, at least 29 cases have been laboratory confirmed, and human-to-human transmission is suspected. Despite posing a significant threat to public health, no treatment or vaccine is available for hantaviral disease. Here, we describe an effort to identify, characterize, and develop neutralizing and protective antibodies against the glycoprotein complex (Gn and Gc) of Andes virus (ANDV), the causative agent of the Epuyén outbreak. Using murine hybridoma technology, we generated 19 distinct monoclonal antibodies (MAbs) against ANDV GnGc. When tested for neutralization against a recombinant vesicular stomatitis virus expressing the Andes glycoprotein (GP) (VSV-ANDV), 12 MAbs showed potent neutralization and 8 showed activity in an antibody-dependent cellular cytotoxicity reporter assay. Escape mutant analysis revealed that neutralizing MAbs targeted both the Gn and the Gc. Four MAbs that bound different epitopes were selected for preclinical studies and were found to be 100% protective against lethality in a Syrian hamster model of ANDV infection. These data suggest the existence of a wide array of neutralizing antibody epitopes on hantavirus GnGc with unique properties and mechanisms of action. IMPORTANCE Infections with New World hantaviruses are associated with high case fatality rates, and no specific vaccine or treatment options exist. Furthermore, the biology of the hantaviral GnGc complex, its antigenicity, and its fusion machinery are poorly understood. Protective monoclonal antibodies against GnGc have the potential to be developed into therapeutics against hantaviral disease and are also great tools to elucidate the biology of the glycoprotein complex.

scholarly journals Andes Virus Antigens Are Shed in Urine of Patients with Acute Hantavirus Cardiopulmonary Syndrome

2009 ◽  
Vol 83 (10) ◽  
pp. 5046-5055 ◽  
Author(s):  
Paula Godoy ◽  
Delphine Marsac ◽  
Elias Stefas ◽  
Pablo Ferrer ◽  
Nicole D. Tischler ◽  
...  
Keyword(s):  
Magnetic Beads ◽  
Survival Rates ◽  
Case Fatality ◽  
Enzyme Linked Immunosorbent Assay ◽  
Highly Pathogenic ◽  
Human Apolipoprotein ◽  
Molecular Approaches ◽  
Apolipoprotein H ◽  
Andes Virus ◽  
Biological Mixtures

ABSTRACT Hantavirus cardiopulmonary syndrome (HCPS) is a highly pathogenic emerging disease (40% case fatality rate) caused by New World hantaviruses. Hantavirus infections are transmitted to humans mainly by inhalation of virus-contaminated aerosol particles of rodent excreta and secretions. At present, there are no antiviral drugs or immunotherapeutic agents available for the treatment of hantaviral infection, and the survival rates for infected patients hinge largely on early virus recognition and hospital admission and aggressive pulmonary and hemodynamic support. In this study, we show that Andes virus (ANDV) interacts with human apolipoprotein H (ApoH) and that ApoH-coated magnetic beads or ApoH-coated enzyme-linked immunosorbent assay plates can be used to capture and concentrate the virus from complex biological mixtures, such as serum and urine, allowing it to be detected by both immunological and molecular approaches. In addition, we report that ANDV-antigens and infectious virus are shed in urine of HCPS patients.

scholarly journals Protective efficacy of a SARS-CoV-2 DNA vaccine in wild-type and immunosuppressed Syrian hamsters

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Rebecca L. Brocato ◽  
Steven A. Kwilas ◽  
Robert K. Kim ◽  
Xiankun Zeng ◽  
Lucia M. Principe ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Phase 1 ◽  
Severe Disease ◽  
Disease Model ◽  
Wild Type ◽  
Jet Injection ◽  
Syrian Hamsters ◽  
Dna Targeting

AbstractA worldwide effort to counter the COVID-19 pandemic has resulted in hundreds of candidate vaccines moving through various stages of research and development, including several vaccines in phase 1, 2 and 3 clinical trials. A relatively small number of these vaccines have been evaluated in SARS-CoV-2 disease models, and fewer in a severe disease model. Here, a SARS-CoV-2 DNA targeting the spike protein and delivered by jet injection, nCoV-S(JET), elicited neutralizing antibodies in hamsters and was protective in both wild-type and transiently immunosuppressed hamster models. This study highlights the DNA vaccine, nCoV-S(JET), we developed has a great potential to move to next stage of preclinical studies, and it also demonstrates that the transiently-immunosuppressed Syrian hamsters, which recapitulate severe and prolonged COVID-19 disease, can be used for preclinical evaluation of the protective efficacy of spike-based COVID-19 vaccines.

scholarly journals Immunization with Epstein–Barr Virus Core Fusion Machinery Envelope Proteins Elicit High Titers of Neutralizing Activities and Protect Humanized Mice from Lethal Dose EBV Challenge

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 285
Author(s):  
Xinle Cui ◽  
Zhouhong Cao ◽  
Yuriko Ishikawa ◽  
Sara Cui ◽  
Ken-Ichi Imadome ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
B Lymphocytes ◽  
Neutralizing Antibodies ◽  
Epstein Barr Virus ◽  
Lethal Dose ◽  
Envelope Proteins ◽  
Humanized Mice ◽  
Target Cells ◽  
Barr Virus ◽  
Epstein Barr

Epstein–Barr virus (EBV) is the primary cause of infectious mononucleosis and is strongly implicated in the etiology of multiple lymphoid and epithelial cancers. EBV core fusion machinery envelope proteins gH/gL and gB coordinately mediate EBV fusion and entry into its target cells, B lymphocytes and epithelial cells, suggesting these proteins could induce antibodies that prevent EBV infection. We previously reported that the immunization of rabbits with recombinant EBV gH/gL or trimeric gB each induced markedly higher serum EBV-neutralizing titers for B lymphocytes than that of the leading EBV vaccine candidate gp350. In this study, we demonstrated that immunization of rabbits with EBV core fusion machinery proteins induced high titer EBV neutralizing antibodies for both B lymphocytes and epithelial cells, and EBV gH/gL in combination with EBV trimeric gB elicited strong synergistic EBV neutralizing activities. Furthermore, the immune sera from rabbits immunized with EBV gH/gL or trimeric gB demonstrated strong passive immune protection of humanized mice from lethal dose EBV challenge, partially or completely prevented death respectively, and markedly decreased the EBV load in peripheral blood of humanized mice. These data strongly suggest the combination of EBV core fusion machinery envelope proteins gH/gL and trimeric gB is a promising EBV prophylactic vaccine.

scholarly journals Do Animals Play a Role in the Transmission of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)? A Commentary

Animals ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 16
Author(s):  
Anna Costagliola ◽  
Giovanna Liguori ◽  
Danila d’Angelo ◽  
Caterina Costa ◽  
Francesca Ciani ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Neutralizing Antibodies ◽  
Experimental Studies ◽  
Infectious Agent ◽  
Human Infection ◽  
Farm Animals ◽  
Partial Protection ◽  
Management Measures ◽  
First Case ◽  
And Behavior

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to the Beta-coronavirus genus. It is 96.2% homologous to bat CoV RaTG13 and 88% homologous to two bat SARS-like coronaviruses. SARS-CoV-2 is the infectious agent responsible for the coronavirus disease (COVID-19), which was first reported in the Hubei province of Wuhan, China, at the beginning of December 2019. Human transmission from COVID-19 patients or incubation carriers occurs via coughing, sneezing, speaking, discharge from the nose, or fecal contamination. Various strains of the virus have been reported around the world, with different virulence and behavior. In addition, SARS-CoV-2 shares certain epitopes with some taxonomically related viruses, with tropism for the most common synanthropic animals. By elucidating the immunological properties of the circulating SARS-CoV-2, a partial protection due to human–animal interactions could be supposed in some situations. In addition, differential epitopes could be used for the differential diagnosis of SARS-CoV-2 infection. There have been cases of transmission from people with COVID-19 to pets such as cats and dogs. In addition, wild felines were infected. All These animals were either asymptomatic or mildly symptomatic and recovered spontaneously. Experimental studies showed cats and ferrets to be more susceptible to COVID-19. COVID-19 positive dogs and felines do not transmit the infection to humans. In contrast, minks at farms were severely infected from people with COVID-19. A SARS-Cov-2 variant in the Danish farmed mink that had been previously infected by COVID-19 positive workers, spread to mink workers causing the first case of animal-to-human infection transmission that causes a moderate decreased sensitivity to neutralizing antibodies. Thus, more investigations are necessary. It remains important to understand the risk that people with COVID-19 pose to their pets, as well as wild or farm animals so effective recommendations and risk management measures against COVID-19 can be made. A One Health unit that facilitates collaboration between public health and veterinary services is recommended.

Sign in / Sign up

Export Citation Format

Share Document