scholarly journals Immunogenicity and Protective Efficacy of a Polyvalent DNA Vaccine against Human Orthopoxvirus Infections Based on Smallpox Virus Genes

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Rinat A. Maksyutov ◽  
Elena V. Gavrilova ◽  
Galina V. Kochneva ◽  
Sergei N. Shchelkunov
Keyword(s):  
Vaccinia Virus ◽  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Dna Vaccines ◽  
Protective Efficacy ◽  
Surface Membrane ◽  
Virus Envelope ◽  
Extracellular Virus ◽  
Rous Sarcoma ◽  
Sarcoma Virus

DNA vaccines combining plasmids carrying the variola virus genes M1R, A30L, and F8L of intracellular virion surface membrane proteins as well as A36R and B7R of the extracellular virus envelope proteins under control of Rous sarcoma virus or cytomegalovirus promoters have been constructed. These DNA vaccines induced production of a high titers of vaccinia virus-neutralizing antibodies in mice similar to those elicited by the live vaccinia virus immunization. Mice vaccinated by created DNA vaccine were completely protected against a lethal (10 LD50) challenge with highly pathogenic ectromelia virus. These results suggest that such vaccine should be efficient in immunization of humans against smallpox.

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.

A mutant of rous sarcoma virus with a thermolabile defect in the virus envelope

Virology ◽  
1978 ◽  
Vol 88 (1) ◽  
pp. 71-81 ◽  
Author(s):  
Franco Tato ◽  
Jennifer A. Beamand ◽  
John A. Wyke
Keyword(s):  
Rous Sarcoma Virus ◽  
Virus Envelope ◽  
Rous Sarcoma ◽  
Sarcoma Virus

scholarly journals A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Lesley C. Dupuy ◽  
Michelle J. Richards ◽  
Brian D. Livingston ◽  
Drew Hannaman ◽  
Connie S. Schmaljohn
Keyword(s):  
Dna Vaccine ◽  
Specific Antibody ◽  
Dna Vaccines ◽  
Protective Efficacy ◽  
Effective Means ◽  
Encephalitis Virus ◽  
Antibody Responses ◽  
Equine Encephalitis Virus ◽  
Virus Specific Antibody ◽  
The Individual

There remains a need for vaccines that can safely and effectively protect against the biological threat agents Venezuelan (VEEV), western (WEEV), and eastern (EEEV) equine encephalitis virus. Previously, we demonstrated that a VEEV DNA vaccine that was optimized for increased antigen expression and delivered by intramuscular (IM) electroporation (EP) elicited robust and durable virus-specific antibody responses in multiple animal species and provided complete protection against VEEV aerosol challenge in mice and nonhuman primates. Here, we performed a comparative evaluation of the immunogenicity and protective efficacy of individual optimized VEEV, WEEV, and EEEV DNA vaccines with that of a 1 : 1 : 1 mixture of these vaccines, which we have termed the 3-EEV DNA vaccine, when delivered by IM EP. The individual DNA vaccines and the 3-EEV DNA vaccine elicited robust and durable virus-specific antibody responses in mice and rabbits and completely protected mice from homologous VEEV, WEEV, and EEEV aerosol challenges. Taken together, the results from these studies demonstrate that the individual VEEV, WEEV, and EEEV DNA vaccines and the 3-EEV DNA vaccine delivered by IM EP provide an effective means of eliciting protection against lethal encephalitic alphavirus infections in a murine model and represent viable next-generation vaccine candidates that warrant further development.

scholarly journals Differential Antigen Requirements for Protection against Systemic and Intranasal Vaccinia Virus Challenges in Mice

2008 ◽  
Vol 82 (14) ◽  
pp. 6829-6837 ◽  
Author(s):  
David R. Kaufman ◽  
Jaap Goudsmit ◽  
Lennart Holterman ◽  
Bonnie A. Ewald ◽  
Matthew Denholtz ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Recombinant Adenovirus ◽  
Protective Efficacy ◽  
Postexposure Prophylaxis ◽  
Virus Challenge ◽  
Protective Antigens ◽  
A Subunit ◽  
Potential Strategy

ABSTRACT The development of a subunit vaccine for smallpox represents a potential strategy to avoid the safety concerns associated with replication-competent vaccinia virus. Preclinical studies to date with subunit smallpox vaccine candidates, however, have been limited by incomplete information regarding protective antigens and the requirement for multiple boost immunizations to afford protective immunity. Here we explore the protective efficacy of replication-incompetent, recombinant adenovirus serotype 35 (rAd35) vectors expressing the vaccinia virus intracellular mature virion (IMV) antigens A27L and L1R and extracellular enveloped virion (EEV) antigens A33R and B5R in a murine vaccinia virus challenge model. A single immunization with the rAd35-L1R vector effectively protected mice against a lethal systemic vaccinia virus challenge. The rAd35-L1R vector also proved more efficacious than the combination of four rAd35 vectors expressing A27L, L1R, A33R, and B5R. Moreover, serum containing L1R-specific neutralizing antibodies afforded postexposure prophylaxis after systemic vaccinia virus infection. In contrast, the combination of rAd35-L1R and rAd35-B5R vectors was required to protect mice against a lethal intranasal vaccinia virus challenge, suggesting that both IMV- and EEV-specific immune responses are important following intranasal infection. Taken together, these data demonstrate that different protective antigens are required based on the route of vaccinia virus challenge. These studies also suggest that rAd vectors warrant further assessment as candidate subunit smallpox vaccines.

scholarly journals Mutagenesis of the palmitoylation site in vaccinia virus envelope glycoprotein B5

2012 ◽  
Vol 93 (4) ◽  
pp. 733-743 ◽  
Author(s):  
María M. Lorenzo ◽  
Juana M. Sánchez-Puig ◽  
Rafael Blasco
Keyword(s):  
Vaccinia Virus ◽  
Protein Interactions ◽  
Intracellular Transport ◽  
Protein Transport ◽  
Transmembrane Domain ◽  
Virus Transmission ◽  
Cytoplasmic Tail ◽  
Type I ◽  
Virus Envelope ◽  
Extracellular Virus

The outer envelope of vaccinia virus extracellular virions is derived from intracellular membranes that, at late times in infection, are enriched in several virus-encoded proteins. Although palmitoylation is common in vaccinia virus envelope proteins, little is known about the role of palmitoylation in the biogenesis of the enveloped virus. We have studied the palmitoylation of B5, a 42 kDa type I transmembrane glycoprotein comprising a large ectodomain and a short (17 aa) cytoplasmic tail. Mutation of two cysteine residues located in the cytoplasmic tail in close proximity to the transmembrane domain abrogated palmitoylation of the protein. Virus mutants expressing non-palmitoylated versions of B5 and/or lacking most of the cytoplasmic tail were isolated and characterized. Cell-to-cell virus transmission and extracellular virus formation were only slightly affected by those mutations. Notably, B5 versions lacking palmitate showed decreased interactions with proteins A33 and F13, but were still incorporated into the virus envelope. Expression of mutated B5 by transfection into uninfected cells showed that both the cytoplasmic tail and palmitate have a role in the intracellular transport of B5. These results indicate that the C-terminal portion of protein B5, while involved in protein transport and in protein–protein interactions, is broadly dispensable for the formation and egress of infectious extracellular virus and for virus transmission.

scholarly journals Generation of a water-soluble oligomeric ectodomain of the Rous sarcoma virus envelope glycoprotein.

1993 ◽  
Vol 67 (11) ◽  
pp. 6889-6892 ◽  
Author(s):  
J M Gilbert ◽  
L D Hernandez ◽  
T Chernov-Rogan ◽  
J M White
Keyword(s):  
Envelope Glycoprotein ◽  
Rous Sarcoma Virus ◽  
Water Soluble ◽  
Virus Envelope ◽  
Rous Sarcoma ◽  
Sarcoma Virus

scholarly journals Small Animal Jet Injection Technique Results in Enhanced Immunogenicity of Hantavirus DNA Vaccines

2020 ◽  
Author(s):  
Rebecca L. Brocato ◽  
Steven A. Kwilas ◽  
Matthew D. Josleyn ◽  
Simon Long ◽  
Xiankun Zeng ◽  
...  
Keyword(s):  
Dna Vaccine ◽  
Dna Vaccines ◽  
Protective Efficacy ◽  
Small Animal ◽  
Antigen Expression ◽  
Injection Technique ◽  
Small Animals ◽  
Jet Injection ◽  
Injection Device ◽  
Hamster Model

AbstractDNA vaccine evaluation in small animals is hampered by low immunogenicity when the vaccines are delivered using a needle and syringe. To overcome this technical hurdle we tested the possibility that a device developed for human intradermal medicine delivery might be adapted to successfully deliver a DNA vaccine to small animals. The PharmaJet® Tropis device is a FDA 510(k)-cleared disposable syringe, needle-free jet injection device designed to administer medicines to the human dermis in a 0.1 mL volume. Here, we found that hantavirus DNA vaccines administered to Syrian hamsters using Tropis were substantially more immunogenic than the same vaccines delivered by needle/syringe or particle mediated epidermal delivery (gene gun) vaccination. By adjusting how the device was used we could deliver vaccine to either subcutaneous tissues, or through the skin into the muscle. RNA and/or antigen expression was detected in epidermal, subepidermal and fibroblast cells. We directly compared six optimized and non-optimized hantavirus DNA vaccines in hamsters. Optimization, including codon-usage and mRNA stability, did not necessarily result in increased immunogenicity for all vaccines tested; however, optimization of the Andes virus (ANDV) DNA vaccine protected vaccinated hamsters from lethal disease. This is the first time active vaccination with an ANDV DNA vaccine has shown protective efficacy in the hamster model. The adaptation of a human intradermal jet injection device for use as a method of subcutaneous and intramuscular jet injection of DNA vaccines will advance the development of nucleic acid based medical countermeasures for diseases modeled in hamsters.

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