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1

Vaccinia virus: a suitable vehicle for recombinant vaccines?  

PubMed

The complications of vaccination against small pox are discussed in relation to the contemplated use as vaccines of recombinant vaccinia viruses carrying the genes for "protective" antigens derived from a range of pathogens. Recombinant vaccines are potentially extremely valuable instruments in the fight against infectious diseases, but caution is needed in their deployment. In addition to the dangers associated with the pathogenicity of various strains of vaccinia virus, there may be problems related to the ecology of the poxviruses--especially orthopoxviruses. Before recombinant vaccinia virus vaccines are widely used, ecological research is urgently needed. It should cover not only the ecology of orthopoxviruses, but also possible interactions between engineered vaccinia viruses released into the environment and wild viruses which may be resident in both target and non-target species in a wide selection of habitats. PMID:2669685

Kaplan, C

1989-01-01

2

VACCINATION OF VAMPIRE BATS USING RECOMBINANT VACCINIA-RABIES VIRUS  

Microsoft Academic Search

Adult vampire bats (Desmodus rotundus) were vaccinated by intramuscular, scarifi- cation, oral, or aerosol routes (n58 in each group) using a vaccinia-rabies glycoprotein recom- binant virus. Sera were obtained before and 30 days after vaccination. All animals were then challenged intramuscularly with a lethal dose of rabies virus. Neutralizing antirabies antibodies were measured by rapid fluorescent focus inhibition test (RFFIT).

Alvaro Aguilar-Setien; Yolanda Leon Campos; Emiliano Tesoro Cruz; Bernard Brochier; Paul-Pierre Pastoret

2002-01-01

3

Vaccinia Virus: A Tool for Research and Vaccine Development  

NASA Astrophysics Data System (ADS)

Vaccinia virus is no longer needed for smallpox immunization, but now serves as a useful vector for expressing genes within the cytoplasm of eukaryotic cells. As a research tool, recombinant vaccinia viruses are used to synthesize biologically active proteins and analyze structure-function relations, determine the targets of humoral- and cell-mediated immunity, and investigate the immune responses needed for protection against specific infectious diseases. When more data on safety and efficacy are available, recombinant vaccinia and related poxviruses may be candidates for live vaccines and for cancer immunotherapy.

Moss, Bernard

1991-06-01

4

Construction of Live Vaccines Using Genetically Engineered Poxviruses: Biological Activity of Vaccinia Virus Recombinants Expressing the Hepatitis B Virus Surface Antigen and the Herpes Simplex Virus Glycoprotein D  

Microsoft Academic Search

Potential live vaccines using recombinant vaccinia viruses have been constructed for both hepatitis B and herpes simplex. These recombinant vaccinia viruses express cloned genes of the hepatitis B virus surface antigen (HBsAg) or the glycoprotein D from herpes simplex virus (HSV-gD). The HBsAg synthesized in vitro under the regulation of vaccinia virus is secreted from infected cells as a particle

Enzo Paoletti; Bernard R. Lipinskas; Carol Samsonoff; Susan Mercer; Dennis Panicali

1984-01-01

5

Recombinant Vaccinia Virus: Immunization against Multiple Pathogens  

NASA Astrophysics Data System (ADS)

The coding sequences for the hepatitis B virus surface antigen, the herpes simplex virus glycoprotein D, and the influenza virus hemagglutinin were inserted into a single vaccinia virus genome. Rabbits inoculated intravenously or intradermally with this polyvalent vaccinia virus recombinant produced antibodies reactive to all three authentic foreign antigens. In addition, the feasibility of multiple rounds of vaccination with recombinant vaccinia virus was demonstrated.

Perkus, Marion E.; Piccini, Antonia; Lipinskas, Bernard R.; Paoletti, Enzo

1985-09-01

6

Vaccinia viruses: vaccines against smallpox and vectors against infectious diseases and tumors  

PubMed Central

Less than 200 years after its introduction, widespread use of vaccinia virus (VACV) as a smallpox vaccine has eradicated variola virus. Along with the remarkable success of the vaccination program, frequent and sometimes severe adverse reactions to VACV were encountered. After eradication, VACV has been reserved for select populations who might be at significant risk for orthopoxvirus infections. Events over the past decade have renewed concerns over the potential use of variola virus as a biological weapon. Accordingly, interest in VACV and attenuated derivatives has increased, both as vaccines against smallpox and as vectors for other vaccines. This article will focus on new developments in the field of orthopoxvirus immunization and will highlight recent advances in the use of vaccinia viruses as vectors for infectious diseases and malignancies. PMID:21854314

Walsh, Stephen R; Dolin, Raphael

2011-01-01

7

Oral Vaccination With Vaccinia Virus Expressing the Tick Antigen Subolesin Inhibits Tick Feeding and Transmission of Borrelia burgdorferi Vaccination  

PubMed Central

Immunization with the Ixodes scapularis protein, subolesin, has previously been shown to protect hosts against tick infestation and to decrease acquisition of Anaplsma marginale and Babesia bigemina. Here we report the efficacy of subolesin expressed from Vaccinia virus for use as an orally delivered reservoir–targeted vaccine for prevention of tick infestation and acquisition/transmission of Borrelia burgdorferi to its tick and mouse hosts. We cloned subolesin into Vaccinia virus and showed that it is expressed from mammalian cells infected with the recombinant virus in vitro. We then vaccinated mice by oral gavage. A single dose of the vaccine was sufficient for mice to generate antibody response to subolesin. Vaccination with the subolesin expressing Vaccinia virus inhibited tick infestation by 52% compared to control vaccination with Vaccinia virus and reduced uptake of B. burgdorferi among the surviving ticks that fed to repletion by 34%. There was a reduction in transmission of B. burgdorferi to uninfected vaccinated mice of 40% compared to controls. These results suggest that subolesin has potential as a component of a reservoir targeted vaccine to decrease B. burgdorferi, Babesia and Anaplasma species infections in their natural hosts. PMID:22864146

Bensaci, Mekki; Bhattacharya, Debaditya; Clark, Roger; Hu, Linden T.

2014-01-01

8

Oral vaccination of the fox against rabies using a live recombinant vaccinia virus.  

PubMed

Rabies, a viral disease affecting all warm-blooded animals, is prevalent in most parts of the world, where it propagates amongst wild animals, particularly the fox and dog. The public health and economic consequences of infection in man and livestock are well known. Attempts to control the disease by vaccinating wild carnivores with inactivated or attenuated rabies virus remain controversial, and we have instead evaluated here the potential of a recombinant vaccinia virus to protect foxes against the disease. We have found that the administration of vaccinia virus (VV) or a recombinant harbouring the rabies surface antigen gene (VVTGgRAB) is innocuous to foxes. The recombinant virus can elicit the production of titers of rabies-neutralizing antibodies equal or superior to those obtained with conventional vaccine, and 10(8) plaque-forming units (PFU) of VVTGgRAB administered subcutaneously, intradermally or orally confers complete protection to severe challenge infection with street rabies virus. PMID:3736663

Blancou, J; Kieny, M P; Lathe, R; Lecocq, J P; Pastoret, P P; Soulebot, J P; Desmettre, P

9

Host range, growth property, and virulence of the smallpox vaccine: Vaccinia virus Tian Tan strain  

SciTech Connect

Vaccinia Tian Tan (VTT) was used as a vaccine against smallpox in China for millions of people before 1980, yet the biological characteristics of the virus remain unclear. We have characterized VTT with respect to its host cell range, growth properties in vitro, and virulence in vivo. We found that 11 of the 12 mammalian cell lines studied are permissive to VTT infection whereas one, CHO-K1, is non-permissive. Using electron microscopy and sequence analysis, we found that the restriction of VTT replication in CHO-K1 is at a step before viral maturation probably due to the loss of the V025 gene. Moreover, VTT is significantly less virulent than vaccinia WR but remains neurovirulent in mice and causes significant body weight loss after intranasal inoculation. Our data demonstrate the need for further attenuation of VTT to serve either as a safer smallpox vaccine or as a live vaccine vector for other pathogens.

Fang Qing [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Yang Lin [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Zhu Weijun [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Liu Li [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Wang Haibo [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Yu Wenbo [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Xiao Genfu [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Tien Po [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Zhang Linqi [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China); Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016 (United States); AIDS Research Center, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing (China); Chen Zhiwei [Modern Virology Research Center and AIDS Center, National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei 430072 (China) and Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY 10016 (United States)]. E-mail: zchen@adarc.org

2005-05-10

10

Reemergence of Vaccinia Virus during Zoonotic Outbreak, Par? State, Brazil  

PubMed Central

In 2010, vaccinia virus caused an outbreak of bovine vaccinia that affected dairy cattle and rural workers in Pará State, Brazil. Genetic analyses identified the virus as distinct from BeAn58058 vaccinia virus (identified in 1960s) and from smallpox vaccine virus strains. These findings suggest spread of autochthonous group 1 vaccinia virus in this region. PMID:24274374

de Assis, Felipe L.; Vinhote, Wagner M.; Barbosa, Jose D.; de Oliveira, Cairo H.S.; de Oliveira, Carlos M.G.; Campos, Karinny F.; Silva, Natalia S.; Trindade, Giliane de Souza

2013-01-01

11

Development of a vaccinia virus based reservoir-targeted vaccine against Yersinia pestis  

PubMed Central

Yersinia pestis, the causative organism of plague, is a zoonotic organism with a worldwide distribution. Although the last plague epidemic occurred in early 1900s, human cases continue to occur due to contact with infected wild animals. In this study, we have developed a reservoir-targeted vaccine against Y. pestis, to interrupt transmission of disease in wild animals as a potential strategy for decreasing human disease. A vaccinia virus delivery system was used to express the F1 capsular protein and the LcrV type III secretion component of Y. pestis as a fusion protein. Here we show that a single dose of this vaccine administered orally, generates a dose-dependent antibody response in mice. Antibody titers peak by 3 weeks after administration and remain elevated for a minimum of 45 weeks. Vaccination provided up to 100% protection against challenge with Y. pestis administered by intranasal challenge at 10 times the lethal dose with protection lasting a minimum of 45 weeks. An orally available, vaccinia virus expressed vaccine against Y. pestis may be a suitable vaccine for a reservoir targeted strategy for the prevention of enzootic plague. PMID:20875494

Bhattacharya, Debaditya; Mecsas, Joan; Hu, Linden T.

2010-01-01

12

Oral vaccination with vaccinia virus expressing the tick antigen subolesin inhibits tick feeding and transmission of Borrelia burgdorferi.  

PubMed

Immunization with the Ixodes scapularis protein, subolesin, has previously been shown to protect hosts against tick infestation and to decrease acquisition of Anaplsma marginale and Babesia bigemina. Here we report the efficacy of subolesin, a conserved tick protein that can act as a regulator of gene expression, expressed from vaccinia virus for use as an orally delivered reservoir - targeted vaccine for prevention of tick infestation and acquisition/transmission of Borrelia burgdorferi to its tick and mouse hosts. We cloned subolesin into vaccinia virus and showed that it is expressed from mammalian cells infected with the recombinant virus in vitro. We then vaccinated mice by oral gavage. A single dose of the vaccine was sufficient for mice to generate antibody response to subolesin. Vaccination with the subolesin expressing vaccinia virus inhibited tick infestation by 52% compared to control vaccination with vaccinia virus and reduced uptake of B. burgdorferi among the surviving ticks that fed to repletion by 34%. There was a reduction in transmission of B. burgdorferi to uninfected vaccinated mice of 40% compared to controls. These results suggest that subolesin has potential as a component of a reservoir targeted vaccine to decrease B. burgdorferi, Babesia and Anaplasma species infections in their natural hosts. PMID:22864146

Bensaci, Mekki; Bhattacharya, Debaditya; Clark, Roger; Hu, Linden T

2012-09-14

13

Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines  

PubMed Central

Despite worldwide eradication of naturally occurring variola virus, smallpox remains a potential threat to both civilian and military populations. New, safe smallpox vaccines are being developed, and there is an urgent need for methods to evaluate vaccine efficacy after immunization. Here we report the identification of an immunodominant HLA-A*0201-restricted epitope that is recognized by cytotoxic CD8+ T cells and conserved among Orthopoxvirus species including variola virus. This finding has permitted analysis and monitoring of epitope-specific T cell responses after immunization and demonstration of the identified T cell specificity in an A*0201-positive human donor. Vaccination of transgenic mice allowed us to compare the immunogenicity of several vaccinia viruses including highly attenuated, replication-deficient modified vaccinia virus Ankara (MVA). MVA vaccines elicited levels of CD8+ T cell responses that were comparable to those induced by the replication-competent vaccinia virus strains. Finally, we demonstrate that MVA vaccination is fully protective against a lethal respiratory challenge with virulent vaccinia virus strain Western Reserve. Our data provide a basis to rationally estimate immunogenicity of safe, second-generation poxvirus vaccines and suggest that MVA may be a suitable candidate. PMID:12518065

Drexler, Ingo; Staib, Caroline; Kastenmuller, Wolfgang; Stevanovic, Stefan; Schmidt, Burkhard; Lemonnier, Francois A.; Rammensee, Hans-Georg; Busch, Dirk H.; Bernhard, Helga; Erfle, Volker; Sutter, Gerd

2003-01-01

14

Active vaccination with vaccinia virus A33 protects mice against lethal vaccinia and ectromelia viruses but not against cowpoxvirus; elucidation of the specific adaptive immune response.  

PubMed

Vaccinia virus protein A33 (A33VACV) plays an important role in protection against orthopoxviruses, and hence is included in experimental multi-subunit smallpox vaccines. In this study we show that single-dose vaccination with recombinant Sindbis virus expressing A33VACV, is sufficient to protect mice against lethal challenge with vaccinia virus WR (VACV-WR) and ectromelia virus (ECTV) but not against cowpox virus (CPXV), a closely related orthopoxvirus. Moreover, a subunit vaccine based on the cowpox virus A33 ortholog (A33CPXV) failed to protect against cowpox and only partially protected mice against VACV-WR challenge. We mapped regions of sequence variation between A33VACV and A33CPXVand analyzed the role of such variations in protection. We identified a single protective region located between residues 104-120 that harbors a putative H-2Kd T cell epitope as well as a B cell epitope - a target for the neutralizing antibody MAb-1G10 that blocks spreading of extracellular virions. Both epitopes in A33CPXV are mutated and predicted to be non-functional. Whereas vaccination with A33VACV did not induce in-vivo CTL activity to the predicted epitope, inhibition of virus spread in-vitro, and protection from lethal VACV challenge pointed to the B cell epitope highlighting the critical role of residue L118 and of adjacent compensatory residues in protection. This epitope's critical role in protection, as well as its modifications within the orthopoxvirus genus should be taken in context with the failure of A33 to protect against CPXV as demonstrated here. These findings should be considered when developing new subunit vaccines and monoclonal antibody based therapeutics against orthopoxviruses, especially variola virus, the etiologic agent of smallpox. PMID:23842430

Paran, Nir; Lustig, Shlomo; Zvi, Anat; Erez, Noam; Israely, Tomer; Melamed, Sharon; Politi, Boaz; Ben-Nathan, David; Schneider, Paula; Lachmi, Batel; Israeli, Ofir; Stein, Dana; Levin, Reuven; Olshevsky, Udy

2013-01-01

15

Biosafety aspects of modified vaccinia virus Ankara (MVA)-based vectors used for gene therapy or vaccination.  

PubMed

The modified vaccinia virus Ankara (MVA) strain is a highly attenuated strain of vaccinia virus that has been demonstrated to be safe for humans. MVA is widely considered as the vaccinia virus strain of choice for clinical investigation because of its high safety profile. It also represents an excellent candidate for use as vector system in recombinant vaccine development for gene delivery or vaccination against infectious diseases or tumours, even in immunocompromised individuals. The use of MVA and recombinant MVA vectors must comply with various regulatory requirements, particularly relating to the assessment of potential risks for human health and the environment. The purpose of the present paper is to highlight some biological characteristics of MVA and MVA-based recombinant vectors and to discuss these from a biosafety point of view in the context of the European regulatory framework for genetically modified organisms with emphasis on the assessment of potential risks associated with environmental release. PMID:22342706

Verheust, Céline; Goossens, Martine; Pauwels, Katia; Breyer, Didier

2012-03-30

16

Immune and histopathological responses in animals vaccinated with recombinant vaccinia viruses that express individual genes of human respiratory syncytial virus.  

PubMed

Previous reports have established that vaccinia virus (VV) recombinants expressing G, F, or N protein of respiratory syncytial (RS) virus protect small animals against intranasal challenge with live RS virus. This work demonstrates that a variety of parameters affect the protection induced by recombinant viruses. The route of vaccination, the subtype of challenge virus, and the species used influenced the antibody titers and extent of protection. During these studies, observations were also made on the subclass of antibody generated, and pulmonary histopathological changes induced by challenge after vaccination were noted. The effect of route of inoculation on host response was examined by vaccinating mice intranasally, intraperitoneally, or by scarification with a recombinant VV expressing the RS virus G glycoprotein. Intranasal vaccination induced 25-fold-higher titers of antibody to RS virus in the lung than the intraperitoneal route did, but both routes resulted in complete suppression of virus replication after intranasal challenge 21 days after vaccination. Scarification was a less effective method of vaccination. The antibody induced by recombinant VV in mice was mostly immunoglobulin G2a (IgG2a) with some IgG2b. No antibody to RS virus was detected in the IgA, IgM, IgG1, or IgG3 subclass irrespective of the vaccination route. The G and F glycoproteins were shown to elicit similar subclasses of antibody. However, animals vaccinated with the G and F vectors differed strikingly in their response to challenge by heterologous virus. Mice or cotton rats vaccinated with recombinant VV carrying the G gene of RS virus were protected against challenge only with homologous subtype A virus. Vaccination with a recombinant VV expressing the F glycoprotein induced protection against both homologous and heterologous subtype B virus challenge. The protection induced in mice was greater than that detected in cotton rats, indicating that the host may also affect immunity. Finally, this report describes histological examination of mouse lungs after vaccination and challenge. Vaccinated mice that were subsequently challenged had significantly greater lung lesion scores than unvaccinated challenged mice. The lesions were primarily peribronchiolar and perivascular infiltrations of polymorphonuclear cells and lymphocytes. Further work will establish whether these pulmonary changes are a desirable immune response to virus invasion or a potential immunopathogenic hazard. The results have important implications for planning a strategy of vaccination against RS virus and emphasize potential dangers that may attend the use of recombinant VV as vaccines. PMID:3316707

Stott, E J; Taylor, G; Ball, L A; Anderson, K; Young, K K; King, A M; Wertz, G W

1987-12-01

17

A mouse-based assay for the pre-clinical neurovirulence assessment of vaccinia virus-based smallpox vaccines.  

PubMed

Post-vaccinal encephalitis, although relatively uncommon, is a known adverse event associated with many live, attenuated smallpox vaccines. Although smallpox vaccination ceased globally in 1980, vaccine manufacture has resumed in response to concerns over the possible use of smallpox virus as an agent of bioterrorism. To better support the production of safer smallpox vaccines, we previously reported the development of a mouse model in which a relatively attenuated vaccine strain (Dryvax) could be discerned from a more virulent laboratory strain (WR). Here we have further tested the performance of this assay by evaluating the neurovirulence of several vaccinia virus-based smallpox vaccines spanning a known range in neurovirulence for humans. Our data indicate that testing of 10-100 pfu of virus in mice following intracranial inoculation reliably assesses the virus's neurovirulence potential for humans. PMID:19896867

Zhang, Cheryl X; Sauder, Christian; Malik, Tahir; Rubin, Steven A

2010-03-01

18

The Novel Replication-defective Vaccinia Virus (Tiantan Strain)-based Hepatitis C Virus Vaccine Induces Robust Immunity in Macaques  

PubMed Central

The induction of a robust neutralizing antibody (nAb) response is likely to be as essential as specific cell-mediated immunity (CMI) against multiple antigens for the development of effective preventive and therapeutic vaccines against hepatitis C virus (HCV) infection in humans. To date, no data on the immunogenicity of the replication-defective vaccinia virus (derived from the Tiantan strain) (rNTV)-based HCV vaccine in primates have been reported. This study describes in detail the immunogenicity of various vaccine candidates in rhesus macaques, including rNTV-based and replication-defective recombinant adenoviral (rAd)–based HCV vaccines, as well as HCV pseudotyped virus-like particles (HCVpp). Our data showed that rAd-HCV vaccine boosting induced robust CMI, while priming or boosting with HCVpp enhanced the antigen-specific nAb response after rAd-HCV vaccination; however, CMI was not enhanced. Vaccination includes rNTV-HCV priming induced robust antigen-specific antibody, particularly nAbs, and CMI responses. Furthermore, more robust and longer-lasting CMI and higher cytokine levels (both Th1 and Th2 types, especially IFN-?) resulted from boosting with rAd-HCV. We conclude that the rNTV-based HCV vaccine induces robust nAbs and CMI when combined with a heterogeneous primer-booster strategy, which shows promise for development of a human HCV vaccine. PMID:23774793

Wen, Bo; Deng, Yao; Chen, Hong; Guan, Jie; Chuai, Xia; Ruan, Li; Kong, Wei; Tan, Wenjie

2013-01-01

19

Infectious vaccinia virus recombinants that express hepatitis B virus surface antigen  

NASA Astrophysics Data System (ADS)

Potential live vaccines against hepatitis B virus have been produced. The coding sequence for hepatitis B virus surface antigen (HBsAg) has been inserted into the vaccinia virus genome under control of vaccinia virus early promoters. Cells infected with these vaccinia virus recombinants synthesize and excrete HBsAg and vaccinated rabbits rapidly produce antibodies to HBsAg.

Smith, Geoffrey L.; Mackett, Michael; Moss, Bernard

1983-04-01

20

Construction of Live Vaccines by Using Genetically Engineered Poxviruses: Biological Activity of Recombinant Vaccinia Virus Expressing Influenza Virus Hemagglutinin  

Microsoft Academic Search

Recombinant vaccinia viruses containing the cloned hemagglutinin (HA) gene from influenza virus were constructed. The biological activity of these poxvirus vectors was demonstrated both in vitro and in vivo. Expression of HA in cells infected with recombinant vaccinia was detected by using specific anti-HA antiserum and 125I-labeled protein A, showing that HA synthesized under the regulation of vaccinia virus was

Dennis Panicali; Stephen W. Davis; Randall L. Weinberg; Enzo Paoletti

1983-01-01

21

Modified Vaccinia Virus Ankara (MVA) as Production Platform for Vaccines against Influenza and Other Viral Respiratory Diseases  

PubMed Central

Respiratory viruses infections caused by influenza viruses, human parainfluenza virus (hPIV), respiratory syncytial virus (RSV) and coronaviruses are an eminent threat for public health. Currently, there are no licensed vaccines available for hPIV, RSV and coronaviruses, and the available seasonal influenza vaccines have considerable limitations. With regard to pandemic preparedness, it is important that procedures are in place to respond rapidly and produce tailor made vaccines against these respiratory viruses on short notice. Moreover, especially for influenza there is great need for the development of a universal vaccine that induces broad protective immunity against influenza viruses of various subtypes. Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as a vaccine platform. MVA can encode one or more foreign antigens and thus functions as a multivalent vaccine. The vector can be used at biosafety level 1, has intrinsic adjuvant capacities and induces humoral and cellular immune responses. However, there are some practical and regulatory issues that need to be addressed in order to develop MVA-based vaccines on short notice at the verge of a pandemic. In this review, we discuss promising novel influenza virus vaccine targets and the use of MVA for vaccine development against various respiratory viruses. PMID:25036462

Altenburg, Arwen F.; Kreijtz, Joost H. C. M.; de Vries, Rory D.; Song, Fei; Fux, Robert; Rimmelzwaan, Guus F.; Sutter, Gerd; Volz, Asisa

2014-01-01

22

Adverse Events Post Smallpox-Vaccination: Insights from Tail Scarification Infection in Mice with Vaccinia virus  

PubMed Central

Adverse events upon smallpox vaccination with fully-replicative strains of Vaccinia virus (VACV) comprise an array of clinical manifestations that occur primarily in immunocompromised patients leading to significant host morbidity/mortality. The expansion of immune-suppressed populations and the possible release of Variola virus as a bioterrorist act have given rise to concerns over vaccination complications should more widespread vaccination be reinitiated. Our goal was to evaluate the components of the host immune system that are sufficient to prevent morbidity/mortality in a murine model of tail scarification, which mimics immunological and clinical features of smallpox vaccination in humans. Infection of C57BL/6 wild-type mice led to a strictly localized infection, with complete viral clearance by day 28 p.i. On the other hand, infection of T and B-cell deficient mice (Rag1?/?) produced a severe disease, with uncontrolled viral replication at the inoculation site and dissemination to internal organs. Infection of B-cell deficient animals (µMT) produced no mortality. However, viral clearance in µMT animals was delayed compared to WT animals, with detectable viral titers in tail and internal organs late in infection. Treatment of Rag1?/? with rabbit hyperimmune anti-vaccinia serum had a subtle effect on the morbidity/mortality of this strain, but it was effective in reduce viral titers in ovaries. Finally, NUDE athymic mice showed a similar outcome of infection as Rag1?/?, and passive transfer of WT T cells to Rag1?/? animals proved fully effective in preventing morbidity/mortality. These results strongly suggest that both T and B cells are important in the immune response to primary VACV infection in mice, and that T-cells are required to control the infection at the inoculation site and providing help for B-cells to produce antibodies, which help to prevent viral dissemination. These insights might prove helpful to better identify individuals with higher risk of complications after infection with poxvirus. PMID:21526210

Mota, Bruno E. F.; Gallardo-Romero, Nadia; Trindade, Giliane; Keckler, M. Shannon; Karem, Kevin; Carroll, Darin; Campos, Marco A.; Vieira, Leda Q.; da Fonseca, Flavio G.; Ferreira, Paulo C. P.; Bonjardim, Claudio A.; Damon, Inger K.; Kroon, Erna G.

2011-01-01

23

Effect of the Deletion of Genes Encoding Proteins of the Extracellular Virion Form of Vaccinia Virus on Vaccine Immunogenicity and Protective Effectiveness in the Mouse Model  

PubMed Central

Antibodies to both infectious forms of vaccinia virus, the mature virion (MV) and the enveloped virion (EV), as well as cell-mediated immune response appear to be important for protection against smallpox. EV virus particles, although more labile and less numerous than MV, are important for dissemination and spread of virus in infected hosts and thus important in virus pathogenesis. The importance of the EV A33 and B5 proteins for vaccine induced immunity and protection in a murine intranasal challenge model was evaluated by deletion of both the A33R and B5R genes in a vaccine-derived strain of vaccinia virus. Deletion of either A33R or B5R resulted in viruses with a small plaque phenotype and reduced virus yields, as reported previously, whereas deletion of both EV protein-encoding genes resulted in a virus that formed small infection foci that were detectable and quantifiable only by immunostaining and an even more dramatic decrease in total virus yield in cell culture. Deletion of B5R, either as a single gene knockout or in the double EV gene knockout virus, resulted in a loss of EV neutralizing activity, but all EV gene knockout viruses still induced a robust neutralizing activity against the vaccinia MV form of the virus. The effect of elimination of A33 and/or B5 on the protection afforded by vaccination was evaluated by intranasal challenge with a lethal dose of either vaccinia virus WR or IHD-J, a strain of vaccinia virus that produces relatively higher amounts of EV virus. The results from multiple experiments, using a range of vaccination doses and virus challenge doses, and using mortality, morbidity, and virus dissemination as endpoints, indicate that the absence of A33 and B5 have little effect on the ability of a vaccinia vaccine virus to provide protection against a lethal intranasal challenge in a mouse model. PMID:23785523

Meseda, Clement A.; Campbell, Joseph; Kumar, Arunima; Garcia, Alonzo D.; Merchlinsky, Michael; Weir, Jerry P.

2013-01-01

24

Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans  

Microsoft Academic Search

In animals, effective immune responses against malignancies and against several infectious pathogens, including malaria, are mediated by T cells. Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally, followed by intradermal recombinant modified vaccinia virus Ankara (MVA), induces high frequencies of interferon (IFN)-?-secreting, antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen, thrombospondin-related

Samuel J McConkey; William H H Reece; Vasee S Moorthy; Daniel Webster; Susanna Dunachie; Geoff Butcher; Jenni M Vuola; Tom J Blanchard; Philip Gothard; Kate Watkins; Carolyn M Hannan; Simone Everaere; Karen Brown; Kent E Kester; James Cummings; Jackie Williams; D Gray Heppner; Ansar Pathan; Katie Flanagan; Nirmalan Arulanantham; Mark T M Roberts; Michael Roy; Geoffrey L Smith; Joerg Schneider; Tim Peto; Robert E Sinden; Sarah C Gilbert; Adrian V S Hill

2003-01-01

25

Immune response in humans after vaccination with vaccinia virus: generation of a virus-specific cytotoxic activity by human peripheral lymphocytes  

PubMed Central

After vaccinia virus vaccination of human volunteers, local indurations developed within 10 days, and regional adenopathy was detected in half of the individuals. Their peripheral blood lymphocytes (PBL) harvested at different days after vaccination showed specific activity against target cells infected with vaccinia virus with a peak activity at day 7. The specificity of the cytotoxic activity was not related to HLA markers, since autologous, homologous, and heterologous infected target cells were lysed with the same efficiency. The cytotoxic activity was caused by PBL that did not rosette with sheep erythrocytes and could be depleted by more than 90 percent by removing Fc receptor-bearing cells. T-cell- depleted PBL showed a one-half to two times greater cytotoxicity than intact PBL. The cytotoxic activity could also be abrogated by more than 95 percent by rabbit Fab(2) anti-human IgG. On the other hand, nonimmune PBL lysed vaccinia-infected target cells in the presence of specific antibodies against vaccinia virus, thus demonstrating that ADCC could be efficient in lysing vaccinia-infected target cells. We conclude that after vaccination, antibody-forming cells arise and provide specific anti-viral antibody and that the cytotoxic cells detected in this reaction are K cells. These experiments suggest that antibody-dependent cell cytotoxicity may be of major importance in the recovery of man to virus infections. PMID:302316

Perrin, LH; Zinkernagel, RM; Oldstone, MBA

1977-01-01

26

A protein-based smallpox vaccine protects mice from vaccinia and ectromelia virus challenges when given as a prime and single boost  

PubMed Central

The heightened concern about the intentional release of variola virus has led to the need to develop safer smallpox vaccines. While subunit vaccine strategies are safer than live virus vaccines, subunit vaccines have been hampered by the need for multiple boosts to confer optimal protection. Here we developed a protein-based subunit vaccine strategy that provides rapid protection in mouse models of orthopoxvirus infections after a prime and single boost. Mice vaccinated with vaccinia virus envelope proteins from the mature virus (MV) and extracellular virus (EV) adjuvanted with CpG-ODN and alum were protected from lethal intranasal challenge with vaccinia virus and the mouse-specific ectromelia virus. Organs from mice vaccinated with three proteins (A33, B5 and L1) and then sacrificed after challenge contained significantly lower titers of virus when compared to control groups of mice that were not vaccinated or that received sub-optimal formulations of the vaccine. Sera from groups of mice obtained prior to challenge had neutralizing activity against the MV and also inhibited comet formation indicating anti-EV activity. Long-term partial protection was also seen in mice challenged with vaccinia virus 6 months after initial vaccinations. Thus, this work represents a step toward the development of a practical subunit smallpox vaccine. PMID:17098336

Xiao, Yuhong; Aldaz-Carroll, Lydia; Ortiz, Alexandra M.; Whitbeck, J. Charles; Alexander, Edward; Lou, Huan; Davis, J. Heather L.; Braciale, Thomas J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Isaacs, Stuart N.

2007-01-01

27

Deletion of immunomodulator C6 from vaccinia virus strain Western Reserve enhances virus immunogenicity and vaccine efficacy  

PubMed Central

Vectors based on vaccinia virus (VACV), the vaccine used to eradicate smallpox, are currently popular candidates for the vaccination against numerous infectious diseases including malaria and AIDS. Although VACV induces robust cellular and humoral responses, enhancing the safety and efficacy of these vectors remains an important area of research. Here, we describe the enhanced immunogenicity of a recombinant VACV Western Reserve (WR) strain lacking the immunomodulatory protein C6 (v?C6). Intradermal infection of mice with v?C6 was shown previously to induce smaller lesions, indicating viral attenuation, and this was confirmed here using a different inoculation dose. In addition, data presented show that vaccination with v?C6 provided better protection against challenge with a lethal dose of VACV WR, indicating this virus is a better vaccine. Increased protection was not due to improved humoral responses, but instead enhanced cytotoxic activity of T-cells 1 month post-inoculation in the spleens of v?C6-vaccinated mice. PMID:23288427

Sumner, Rebecca P.; Ren, Hongwei

2013-01-01

28

Deletion of immunomodulator C6 from vaccinia virus strain Western Reserve enhances virus immunogenicity and vaccine efficacy.  

PubMed

Vectors based on vaccinia virus (VACV), the vaccine used to eradicate smallpox, are currently popular candidates for the vaccination against numerous infectious diseases including malaria and AIDS. Although VACV induces robust cellular and humoral responses, enhancing the safety and efficacy of these vectors remains an important area of research. Here, we describe the enhanced immunogenicity of a recombinant VACV Western Reserve (WR) strain lacking the immunomodulatory protein C6 (v?C6). Intradermal infection of mice with v?C6 was shown previously to induce smaller lesions, indicating viral attenuation, and this was confirmed here using a different inoculation dose. In addition, data presented show that vaccination with v?C6 provided better protection against challenge with a lethal dose of VACV WR, indicating this virus is a better vaccine. Increased protection was not due to improved humoral responses, but instead enhanced cytotoxic activity of T-cells 1 month post-inoculation in the spleens of v?C6-vaccinated mice. PMID:23288427

Sumner, Rebecca P; Ren, Hongwei; Smith, Geoffrey L

2013-05-01

29

Discovery of Naturally Processed and HLA-Presented Class I Peptides from Vaccinia Virus Infection using Mass Spectrometry for Vaccine Development  

PubMed Central

An important approach for developing a safer smallpox vaccine is to identify naturally processed immunogenic vaccinia-derived peptides rather than live whole vaccinia virus. We used two-dimensional liquid chromatography coupled to mass spectrometry to identify 116 vaccinia peptides, encoded by 61 open reading frames, from a B-cell line (homozygous for HLA class I A*0201, B*1501, and C*03) after infection with vaccinia virus (Dryvax). Importantly, 68 of these peptides are conserved in variola, providing insight into the peptides that induce protection against smallpox. Twenty-one of these 68 conserved peptides were 11 amino acids long or longer, outside of the range of most predictive algorithms. Thus, direct identification of naturally processed and presented HLA peptides gives important information not provided by current computational methods for identifying potential vaccinia epitopes. PMID:19822231

Johnson, Kenneth L.; Ovsyannikova, Inna G.; Mason, Christopher J.; Bergen, H. Robert; Poland, Gregory A.

2009-01-01

30

Protective properties of vaccinia virus-based vaccines: skin scarification promotes a nonspecific immune response that protects against orthopoxvirus disease.  

PubMed

The process of vaccination introduced by Jenner generated immunity against smallpox and ultimately led to the eradication of the disease. Procedurally, in modern times, the virus is introduced into patients via a process called scarification, performed with a bifurcated needle containing a small amount of virus. What was unappreciated was the role that scarification itself plays in generating protective immunity. In rabbits, protection from lethal disease is induced by intradermal injection of vaccinia virus, whereas a protective response occurs within the first 2 min after scarification with or without virus, suggesting that the scarification process itself is a major contributor to immunoprotection. importance: These results show the importance of local nonspecific immunity in controlling poxvirus infections and indicate that the process of scarification should be critically considered during the development of vaccination protocols for other infectious agents. PMID:24760885

Rice, Amanda D; Adams, Mathew M; Lindsey, Scott F; Swetnam, Daniele M; Manning, Brandi R; Smith, Andrew J; Burrage, Andrew M; Wallace, Greg; MacNeill, Amy L; Moyer, Richard W

2014-07-01

31

Induction of Antibody Responses to African Horse Sickness Virus (AHSV) in Ponies after Vaccination with Recombinant Modified Vaccinia Ankara (MVA)  

PubMed Central

Background African horse sickness virus (AHSV) causes a non-contagious, infectious disease in equids, with mortality rates that can exceed 90% in susceptible horse populations. AHSV vaccines play a crucial role in the control of the disease; however, there are concerns over the use of polyvalent live attenuated vaccines particularly in areas where AHSV is not endemic. Therefore, it is important to consider alternative approaches for AHSV vaccine development. We have carried out a pilot study to investigate the ability of recombinant modified vaccinia Ankara (MVA) vaccines expressing VP2, VP7 or NS3 genes of AHSV to stimulate immune responses against AHSV antigens in the horse. Methodology/Principal Findings VP2, VP7 and NS3 genes from AHSV-4/Madrid87 were cloned into the vaccinia transfer vector pSC11 and recombinant MVA viruses generated. Antigen expression or transcription of the AHSV genes from cells infected with the recombinant viruses was confirmed. Pairs of ponies were vaccinated with MVAVP2, MVAVP7 or MVANS3 and both MVA vector and AHSV antigen-specific antibody responses were analysed. Vaccination with MVAVP2 induced a strong AHSV neutralising antibody response (VN titre up to a value of 2). MVAVP7 also induced AHSV antigen–specific responses, detected by western blotting. NS3 specific antibody responses were not detected. Conclusions This pilot study demonstrates the immunogenicity of recombinant MVA vectored AHSV vaccines, in particular MVAVP2, and indicates that further work to investigate whether these vaccines would confer protection from lethal AHSV challenge in the horse is justifiable. PMID:19543394

Maan, Sushila; Rao, Shujing; Mertens, Peter; Blacklaws, Barbara; Davis-Poynter, Nick; Wood, James; Castillo-Olivares, Javier

2009-01-01

32

Vaccinia and other viruses with available vaccines show marked homology with the HIV-1 envelope glycoprotein: the prospect of using existing vaccines to stem the AIDS pandemic.  

PubMed

Cross-reactive immunity occurs when infection with or vaccination against one virus protects against another related family member. A search for homologues of the HIV-1 envelope glycoprotein revealed that it is composed of thousands of intercalating and overlapping viral matches of pentapeptide or longer gapped consensi, belonging to over 70% of the currently sequenced virome, infecting all kingdoms from bacteria to man. It was also highly homologous to proteins from the Visna/Maedi and other ovine viruses, while other proteins (nef/tat/gag/pol) were homologous to proteins from the equine infectious anaemia virus and HTLV-2/HTLV-3 viruses. This phenomenon suggests that horizontal gene transfer from coinfecting RNA and DNA viruses to retroviruses is extensive, providing a route for the subsequent insertion of non-retroviral genes into human and other genomes via retroviral integration. This homology includes all viruses for which vaccines already exist. Cross-reactive immunity may be operative in AIDS, as Vaccinia vaccination decreases viral replication in HIV-1 infected patients' cells, for the CCR5 tropic form. Measles, Dengue virus, or GB virus C infections also decrease the HIV-1 viral load. A resumption of Vaccinia/smallpox vaccination might be expected to have a significant effect on the AIDS pandemic, and a careful study of the potential uses of other existing viral and bacterial vaccines merits close attention. This phenomenon may also be relevant to other recalcitrant viruses, bacteria, and parasites for which no vaccine exists and the armory of existing vaccines may have a role to play in diseases other than those for which they were designed. PMID:21851326

Carter, C J Chris

2012-04-01

33

Adjuvant-like Effect of Vaccinia Virus 14K Protein: A Case Study with Malaria Vaccine Based on the Circumsporozoite Protein  

PubMed Central

Development of subunit vaccines for malaria that elicit a strong, long-term memory response is an intensive area of research, with the focus on improving the immunogenicity of a circumsporozoite (CS) protein-based vaccine. In this study, we found that a chimeric protein, formed by fusing vaccinia virus protein 14K (A27) to the CS of Plasmodium yoelii, induces strong effector memory CD8+ T cell responses in addition to high-affinity Abs when used as a priming agent in the absence of any adjuvant, followed by an attenuated vaccinia virus boost expressing CS in murine models. Moreover, priming with the chimeric protein improved the magnitude and polyfunctionality of cytokine-secreting CD8+ T cells. This fusion protein formed oligomers/aggregates that led to activation of STAT-1 and IFN regulatory factor-3 in human macrophages, indicating a type I IFN response, resulting in NO, IL-12, and IL-6 induction. Furthermore, this vaccination regimen inhibited the liver stage development of the parasite, resulting in sterile protection. In summary, we propose a novel approach in designing CS based pre-erythrocytic vaccines against Plasmodium using the adjuvant-like effect of the immunogenic vaccinia virus protein 14K. PMID:22615208

Vijayan, Aneesh; Gomez, Carmen E.; Espinosa, Diego A.; Goodman, Alan G.; Sanchez-Sampedro, Lucas; Sorzano, Carlos Oscar S.; Zavala, Fidel; Esteban, Mariano

2014-01-01

34

Vaccinia virus-based multivalent H5N1 avian influenza vaccines adjuvanted with IL-15 confer sterile cross-clade protection in mice.  

PubMed

The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of the highly pathogenic avian influenza A H5N1 in both wild bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people. We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune stimulatory cytokine IL-15. The pentavalent Wyeth/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from the H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and N1 neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing Abs and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with the H5N1 virus of a different clade. In addition to having potential as a universal influenza vaccine, in the event of an impending pandemic the Wyeth/IL-15/5Flu is also readily amenable to bulk production to cover the global population. For those individuals for whom the use of the Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago. PMID:19234203

Poon, Leo L M; Leung, Y H Connie; Nicholls, John M; Perera, Pin-Yu; Lichy, Jack H; Yamamoto, Masafumi; Waldmann, Thomas A; Peiris, J S Malik; Perera, Liyanage P

2009-03-01

35

L1R, A27L, A33R and B5R vaccinia virus genes expressed by fowlpox recombinants as putative novel orthopoxvirus vaccines  

PubMed Central

Background The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of the absence of new smallpox cases. However, the development of an effective prophylactic vaccine against smallpox is still necessary, to protect from the threat of deliberate release of the variola virus for bioterrorism and from new zoonotic infections, and to improve the safety of the traditional vaccine. Preventive vaccination still remains the most effective control and new vectors have been developed to generate recombinant vaccines against smallpox that induce the same immunogenicity as the traditional one. As protective antibodies are mainly directed against the surface proteins of the two infectious forms of vaccinia, the intracellular mature virions and the extracellular virions, combined proteins from these viral forms can be used to better elicit a complete and protective immunity. Methods Four novel viral recombinants were constructed based on the fowlpox genetic background, which independently express the vaccinia virus L1 and A27 proteins present on the mature virions, and the A33 and B5 proteins present on the extracellular virions. The correct expression of the transgenes was determined by RT-PCR, Western blotting, and immunofluorescence. Results and conclusions Using immunoprecipitation and Western blotting, the ability of the proteins expressed by the four novel FPL1R, FPA27L, FPA33R and FPB5R recombinants to be recognized by VV-specific hyperimmune mouse sera was demonstrated. By neutralisation assays, recombinant virus particles released by infected chick embryo fibroblasts were shown not be recognised by hyperimmune sera. This thus demonstrates that the L1R, A27L, A33R and B5R gene products are not inserted into the new viral progeny. Fowlpox virus replicates only in avian species, but it is permissive for entry and transgene expression in mammalian cells, while being immunologically non–cross-reactive with vaccinia virus. These recombinants might therefore represent safer and more promising immunogens that can circumvent neutralisation by vector-generated immunity in smallpox-vaccine-experienced humans. PMID:23578094

2013-01-01

36

Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity  

NASA Astrophysics Data System (ADS)

Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

1999-04-01

37

Modified Vaccinia Virus Ankara Induces Toll-Like Receptor-Independent Type I Interferon Responses  

Microsoft Academic Search

Modified vaccinia virus Ankara (MVA) is a highly attenuated vaccinia virus strain undergoing clinical evaluation as a replication-deficient vaccine vector against various infections and tumor diseases. To analyze the basis of its high immunogenicity, we investigated the mechanism of how MVA induces type I interferon (IFN) responses. MVA stimulation of bone marrow-derived dendritic cells (DC) showed that plasmacytoid DC were

Zoe Waibler; Martina Anzaghe; Holger Ludwig; Shizuo Akira; Siegfried Weiss; Gerd Sutter; Ulrich Kalinke

2007-01-01

38

The combination of marker gene swapping and fluorescence-activated cell sorting improves the efficiency of recombinant modified vaccinia virus Ankara vaccine production for human use.  

PubMed

Modified vaccinia virus Ankara (MVA) is employed as a human vaccine vector for the high expression of heterologous genes and the lack of replication in mammalian cells. This study demonstrates that cells infected by recombinant viruses can be obtained by fluorescence-activated cell sorting. Recombinant viruses are generated by a swapping event between a red fluorescent protein gene in the acceptor virus and a plasmid cassette coding for both a green fluorescent marker and a transgene. To prevent the carry-over of parental virus, due to superinfection of the cells harbouring recombinant viruses, the sorting is performed on cells infected at low m.o.i. in the presence of a reversible inhibitor of viral particle release. Terminal dilution cloning is then used to isolate both green and marker-free recombinant viruses, which can be identified by whole-plate fluoroimaging. The differential visualization of all the viral types involved allows a stepwise monitoring of all recombinations and leads to a straightforward and efficient flow cytometry-based cell sorting purification protocol. As an example of the efficacy of this sorting procedure, the construction of rMVA's coding for the rat nuclear protein HMGB1 and H5N1 influenza A virus hemagglutinin is reported. The entire recombinant MVA production process is carried out in serum-free media employing primary chicken embryo fibroblasts (CEF), which are certified for the preparation of human vaccines. This rMVA production method is faster, simpler and more reliable than any other available procedure for obtaining safe vaccine stocks for human use. PMID:19778556

Di Lullo, Giulia; Soprana, Elisa; Panigada, Maddalena; Palini, Alessio; Agresti, Alessandra; Comunian, Claudio; Milani, Adelaide; Capua, Ilaria; Erfle, Volker; Siccardi, Antonio G

2010-02-01

39

Protective efficacy of Modified Vaccinia virus Ankara in preclinical studies.  

PubMed

Modified Vaccinia virus Ankara (MVA) is a tissue culture-derived, highly attenuated strain of vaccinia virus (VACV) exhibiting characteristic defective replication in cells from mammalian hosts. In the 1960s MVA was originally generated as a candidate virus for safer vaccination against smallpox. Now, MVA is widely used in experimental vaccine development targeting important infectious diseases and cancer. Versatile technologies for genetic engineering, large-scale production, and quality control facilitate R&D of recombinant and non-recombinant MVA vaccines matching today's requirements for new biomedical products. Such vaccines are attractive candidates for delivering antigens from pathogens against which no, or no effective vaccine is available, including emerging infections caused by highly pathogenic influenza viruses, chikungunya virus, West Nile virus or zoonotic orthopoxviruses. Other directions are seeking valuable vaccines against highly complex diseases such as AIDS, malaria, and tuberculosis. Here, we highlight examples of MVA candidate vaccines against infectious diseases, and review the efforts made to assess both the efficacy of vaccination and immune correlates of protection in preclinical studies. PMID:23523402

Volz, Asisa; Sutter, Gerd

2013-09-01

40

Immune control strategies for vaccinia virus-related laboratory-acquired infections.  

PubMed

While presenting biological characteristics of vaccinia virus and laboratory-acquired infections during related research processes, this paper focuses on benefits and risks of vaccinia virus immunization in relation to laboratory-acquired infections, describes characteristics and the adaptation of vaccinia virus vaccine, analyses the role vaccinia virus immunization plays in the prevention and control of laboratory-acquired infections, and finally proposes solutions and countermeasures to further promote and implement immune control strategies. The problem related to immune strategy and laboratory- acquired infections which is being raised, analyzed and explored plays an active and instructive role in vaccinia virus related researches and laboratory- acquired infections, and also helps to recommend and develop relevant immune strategy for future vaccine control of such infections. PMID:24625408

Wei, Qiang; Jiang, Meng Nan; Han, Jun; Wang, Zi Jun

2014-02-01

41

Attenuated and replication-competent vaccinia virus strains M65 and M101 with distinct biology and immunogenicity as potential vaccine candidates against pathogens.  

PubMed

Replication-competent poxvirus vectors with an attenuation phenotype and with a high immunogenic capacity of the foreign expressed antigen are being pursued as novel vaccine vectors against different pathogens. In this investigation, we have examined the replication and immunogenic characteristics of two vaccinia virus (VACV) mutants, M65 and M101. These mutants were generated after 65 and 101 serial passages of persistently infected Friend erythroleukemia (FEL) cells. In cultured cells of different origins, the mutants are replication competent and have growth kinetics similar to or slightly reduced in comparison with those of the parental Western Reserve (WR) virus strain. In normal and immune-suppressed infected mice, the mutants showed different levels of attenuation and pathogenicity in comparison with WR and modified vaccinia Ankara (MVA) strains. Wide genome analysis after deep sequencing revealed selected genomic deletions and mutations in a number of viral open reading frames (ORFs). Mice immunized in a DNA prime/mutant boost regimen with viral vectors expressing the LACK (Leishmania homologue for receptors of activated C kinase) antigen of Leishmania infantum showed protection or a delay in the onset of cutaneous leishmaniasis. Protection was similar to that triggered by MVA-LACK. In immunized mice, both polyfunctional CD4(+) and CD8(+) T cells with an effector memory phenotype were activated by the two mutants, but the DNA-LACK/M65-LACK protocol preferentially induced CD4(+) whereas DNA-LACK/M101-LACK preferentially induced CD8(+) T cell responses. Altogether, our findings showed the adaptive changes of the WR genome during long-term virus-host cell interaction and how the replication competency of M65 and M101 mutants confers distinct biological properties and immunogenicity in mice compared to those of the MVA strain. These mutants could have applicability for understanding VACV biology and as potential vaccine vectors against pathogens and tumors. PMID:23596295

Sánchez-Sampedro, Lucas; Gómez, Carmen Elena; Mejías-Pérez, Ernesto; Pérez-Jiménez, Eva; Oliveros, Juan Carlos; Esteban, Mariano

2013-06-01

42

Vaccinia Virus Recombinant Expressing Herpes Simplex Virus Type 1 Glycoprotein D Prevents Latent Herpes in Mice  

Microsoft Academic Search

In humans, herpes simplex virus causes a primary infection and then often a latent ganglionic infection that persists for life. Because these latent infections can recur periodically, vaccines are needed that can protect against both primary and latent herpes simplex infections. Infectious vaccinia virus recombinants that contain the herpes simplex virus type 1 (HSV-1) glycoprotein D gene under control of

Kenneth J. Cremer; Michael Mackett; Charles Wohlenberg; Abner Louis Notkins; Bernard Moss

1985-01-01

43

Fighting cancer with vaccinia virus: teaching new tricks to an old dog.  

PubMed

Vaccinia virus has played a huge part in human beings' victory over smallpox. With smallpox being eradicated and large-scale vaccination stopped worldwide, vaccinia has assumed a new role in our fight against another serious threat to human health: cancer. Recent advances in molecular biology, virology, immunology, and cancer genetics have led to the design of novel cancer therapeutics based on vaccinia virus backbones. With the ability to infect efficiently a wide range of host cells, a genome that can accommodate large DNA inserts and express multiple genes, high immunogenicity, and cytoplasmic replication without the possibility of chromosomal integration, vaccinia virus has become the platform of many exploratory approaches to treat cancer. Vaccinia virus has been used as (1) a delivery vehicle for anti-cancer transgenes, (2) a vaccine carrier for tumor-associated antigens and immunoregulatory molecules in cancer immunotherapy, and (3) an oncolytic agent that selectively replicates in and lyses cancer cells. PMID:15668130

Shen, Yuqiao; Nemunaitis, John

2005-02-01

44

MORPHOLOGICAL STRUCTURE OF THE VIRUS OF VACCINIA  

PubMed Central

The pictorial data obtained by means of the electron microscope indicate a remarkable regularity in the morphology of the elementary body of vaccinia. The virus particles apparently have internal structure and some sort of limiting membrane. PMID:19871212

Green, R. H.; Anderson, T. F.; Smadel, J. E.

1942-01-01

45

Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development  

Microsoft Academic Search

Summal~ There is considerable interest in designing an effective vaccine to the ubiquitous Epstein-Barr virus (EBV). An important role for EBV-specific cytotoxic T lymphocytes (CTLs) in eliminating virus-infected cells is well established. Limited studies using a small number of immune donors have defined target epitopes within the latent antigens of EBV. The present study provides an extensive analysis of the

R. Khanna; S. t L. Burrows; M. G. Kuri; C. A. Jacob; I. S. Misko; T. B. Scul; E. Kieff; D. J. Moss

1992-01-01

46

From Crescent to Mature Virion: Vaccinia Virus Assembly and Maturation  

PubMed Central

Vaccinia virus (VACV) has achieved unprecedented success as a live viral vaccine for smallpox which mitigated eradication of the disease. Vaccinia virus has a complex virion morphology and recent advances have been made to answer some of the key outstanding questions, in particular, the origin and biogenesis of the virion membrane, the transformation from immature virion (IV) to mature virus (MV), and the role of several novel genes, which were previously uncharacterized, but have now been shown to be essential for VACV virion formation. This new knowledge will undoubtedly contribute to the rational design of safe, immunogenic vaccine candidates, or effective antivirals in the future. This review endeavors to provide an update on our current knowledge of the VACV maturation processes with a specific focus on the initiation of VACV replication through to the formation of mature virions. PMID:25296112

Liu, Liang; Cooper, Tamara; Howley, Paul M.; Hayball, John D.

2014-01-01

47

A Novel Cellular Protein, VPEF, Facilitates Vaccinia Virus Penetration into HeLa Cells through Fluid Phase Endocytosis  

Microsoft Academic Search

Vaccinia virus is a large DNA virus that infects many cell cultures in vitro and animal species in vivo. Although it has been used widely as a vaccine, its cell entry pathway remains unclear. In this study, we showed that vaccinia virus intracellular mature virions bound to the filopodia of HeLa cells and moved toward the cell body and entered

Cheng-Yen Huang; Tsai-Yi Lu; Chi-Horng Bair; Yuan-Shau Chang; Jeng-Kuan Jwo; Wen Chang

2008-01-01

48

A Modified Vaccinia Ankara Virus (MVA) Vaccine Expressing African Horse Sickness Virus (AHSV) VP2 Protects Against AHSV Challenge in an IFNAR -/- Mouse Model  

PubMed Central

African horse sickness (AHS) is a lethal viral disease of equids, which is transmitted by Culicoides midges that become infected after biting a viraemic host. The use of live attenuated vaccines has been vital for the control of this disease in endemic regions. However, there are safety concerns over their use in non-endemic countries. Research efforts over the last two decades have therefore focused on developing alternative vaccines based on recombinant baculovirus or live viral vectors expressing structural components of the AHS virion. However, ethical and financial considerations, relating to the use of infected horses in high biosecurity installations, have made progress very slow. We have therefore assessed the potential of an experimental mouse-model for AHSV infection for vaccine and immunology research. We initially characterised AHSV infection in this model, then tested the protective efficacy of a recombinant vaccine based on modified vaccinia Ankara expressing AHS-4 VP2 (MVA-VP2). PMID:21298069

Castillo-Olivares, Javier; Calvo-Pinilla, Eva; Casanova, Isabel; Bachanek-Bankowska, Katarzyna; Chiam, Rachael; Maan, Sushila; Nieto, Jose Maria; Ortego, Javier; Mertens, Peter Paul Clement

2011-01-01

49

A Consecutive Priming-Boosting Vaccination of Mice with Simian Immunodeficiency Virus (SIV) gag/pol DNA and Recombinant Vaccinia Virus Strain DIs Elicits Effective Anti-SIV Immunity  

PubMed Central

To evaluate immunity induced by a novel DNA prime-boost regimen, we constructed a DNA plasmid encoding the gag and pol genes from simian immunodeficiency virus (SIV) (SIVgag/pol DNA), in addition to a replication-deficient vaccinia virus strain DIs recombinant expressing SIV gag and pol genes (rDIsSIVgag/pol). In mice, priming with SIVgag/pol DNA, followed by rDIsSIVgag/pol induced an SIV-specific lymphoproliferative response that was mediated by a CD4+-T-lymphocyte subset. Immunization with either vaccine alone was insufficient to induce high levels of proliferation or Th1 responses in the animals. The prime-boost regimen also induced SIV Gag-specific cellular responses based on gamma interferon secretion, as well as cytotoxic-T-lymphocyte responses. Thus, the regimen of DNA priming and recombinant DIs boosting induced Th1-type cell-mediated immunity, which was associated with resistance to viral challenge with wild-type vaccinia virus expressing SIVgag/pol, suggesting that this new regimen may hold promise as a safe and effective vaccine against human immunodeficiency virus type 1. PMID:15331719

Someya, Kenji; Xin, Ke-Qin; Matsuo, Kazuhiro; Okuda, Kenji; Yamamoto, Naoki; Honda, Mitsuo

2004-01-01

50

Stable Antigen Is Most Effective for Eliciting CD8+ T-Cell Responses after DNA Vaccination and Infection with Recombinant Vaccinia Virus In Vivo  

PubMed Central

The induction of strong CD8+ T-cell responses against infectious diseases and cancer has remained a major challenge. Depending on the source of antigen and the infectious agent, priming of CD8+ T cells requires direct and/or cross-presentation of antigenic peptides on major histocompatibility complex (MHC) class I molecules by professional antigen-presenting cells (APCs). However, both pathways show distinct preferences concerning antigen stability. Whereas direct presentation was shown to efficiently present peptides derived from rapidly degraded proteins, cross-presentation is dependent on long-lived antigen species. In this report, we analyzed the role of antigen stability on DNA vaccination and recombinant vaccinia virus (VV) infection using altered versions of the same antigen. The long-lived nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) can be targeted for degradation by N-terminal fusion to ubiquitin or, as we show here, to the ubiquitin-like modifier FAT10. Direct presentation by cells either transfected with NP-encoding plasmids or infected with recombinant VV in vitro was enhanced in the presence of short-lived antigens. In vivo, however, the highest induction of NP-specific CD8+ T-cell responses was achieved in the presence of long-lived NP. Our experiments provide evidence that targeting antigens for proteasomal degradation does not improve the immunogenicity of DNA vaccines and recombinant VVs. Rather, it is the long-lived antigen that is superior for the efficient activation of MHC class I-restricted immune responses in vivo. Hence, our results suggest a dominant role for antigen cross-priming in DNA vaccination and recombinant VV infection. PMID:22761378

Schliehe, Christopher; Bitzer, Annegret; van den Broek, Maries

2012-01-01

51

Environmental persistence of vaccinia virus on materials.  

PubMed

Smallpox is caused by the variola virus, and ranks as one of the most serious diseases that could originate from a biological weapon. However, limited data exist on the persistence of variola and related viruses on materials (that may act as fomites), under controlled environmental conditions. To fill these data gaps, we determined the persistence of the vaccinia virus (an established surrogate for the variola virus) as a function of temperature, relative humidity and material. Experiments were conducted with vaccinia virus in a freeze-dried form, using four materials under four sets of environmental conditions. After elapsed times ranging from 1 to 56 days, the virus was extracted from small coupons and quantified via plaque-forming units (PFU). The vaccinia virus was most persistent at low temperature and low relative humidity, with greater than 10(4) PFU recovered from glass, galvanized steel and painted cinder block at 56 days (equivalent to only a c. 2 log reduction). Thus, vaccinia virus may persist from weeks to months, depending on the material and environmental conditions. This study may aid those responsible for infection control to make informed decisions regarding the need for environmental decontamination following the release of an agent such as variola. PMID:23815079

Wood, J P; Choi, Y W; Wendling, M Q; Rogers, J V; Chappie, D J

2013-11-01

52

Easy and efficient protocols for working with recombinant vaccinia virus MVA.  

PubMed

Modified vaccinia virus Ankara (MVA) is a highly attenuated and replication-deficient strain of vaccinia virus that is increasingly used as vector for expression of recombinant genes in the research laboratory and in biomedicine for vaccine development. Major benefits of MVA include the clear safety advantage compared to conventional vaccinia viruses, the longstanding experience in the genetic engineering of the virus, and the availability of established procedures for virus production at an industrial scale. MVA vectors can be handled under biosafety level 1 conditions, and a multitude of recombinant MVA vaccines has proven to be immunogenic and protective when delivering various heterologous antigens in animals and humans. In this chapter we provide convenient state-of-the-art protocols for generation, amplification, and purification of recombinant MVA viruses. Importantly, we include methodology for rigid quality control to obtain best possible vector viruses for further investigations including clinical evaluation. PMID:22688761

Kremer, Melanie; Volz, Asisa; Kreijtz, Joost H C M; Fux, Robert; Lehmann, Michael H; Sutter, Gerd

2012-01-01

53

Enhancement of vaccinia vaccine potency by linkage of tumor antigen gene to gene encoding calreticulin.  

PubMed

Vaccinia vaccines have become important vectors for antigen-specific immunotherapy. Calreticulin has been shown to enhance MHC class I presentation of linked peptide/protein and may be useful for antigen-specific cancer treatment. An innovative vaccine administering antigen linked to calreticulin via a vaccinia vector may generate a potent antigen-specific antitumor response. We tested the efficacy of linking calreticulin (CRT) to model antigen human papilloma virus type 16 (HPV-16) E7 in the context of a vaccinia vaccine (Vac-CRT/E7). Intraperitoneal vaccination of C57BL/6 mice with Vac-CRT/E7 led to a dramatic increase in E7-specific IFN-gamma-secreting CD8+ T cells and a potent antitumor effect against E7-expressing tumors compared to immunization with Vac-E7 or Vac-CRT. When compared to other chimeric vaccinia vaccines employing various intracellular targeting strategies previously developed in our lab, Vac-CRT/E7 elicited the highest number of E7-specific CD8+ T cells. Thus, vaccination with vaccinia expressing CRT linked to a tumor antigen may represent an advantageous strategy for cancer immunotherapy. PMID:15364449

Hsieh, Chia-Jung; Kim, Tae Woo; Hung, Chien-Fu; Juang, Jeremy; Moniz, Michelle; Boyd, David A K; He, Liangmei; Chen, Pei-Jer; Chen, Chien-Hung; Wu, T-C

2004-09-28

54

[Immunobiological properties of vp24 protein of Ebola virus expressed by recombinant vaccinia virus].  

PubMed

Immunological and biochemical parameters were studied in guinea pigs immunized with recombinant vaccinia virus containing full-sized gene of Ebola virus vp24 protein and then infected with virulent strain of Ebola virus. The majority of the studied parameters changed similarly in guinea pigs immunized with recombinant vaccinia virus and control guinea pigs inoculated with vaccinia virus both before and after challenge with Ebola virus. However, in animals immunized with recombinant vaccinia virus producing vp24 some biochemical parameters, the mean life span after challenge with Ebola virus, the level of antibodies to the virus, and the phagocytic activity of neutrophils indicated the development of immunological processes other than in controls, namely, the development of immune response to vp24. Although these processes did not eventually lead to the survival of animals, they prolonged the mean life span and resulted in the production of anti-Ebola antibodies, though the level thereof was low. These data demonstrate that recombinant vaccines against Ebola fever are a promising trend of research. PMID:9297340

Chepurnov, A A; Ternovo?, V A; Dadaeva, A A; Dmitriev, I P; Sizikova, L P; Volchkov, V E; Kudoiarova, N M; Rudzevich, T N; Netesov, S V

1997-01-01

55

Vaccinia recombinant virus expressing the rabies virus glycoprotein: safety and efficacy trials in Canadian wildlife.  

PubMed

Twenty-six meadow voles (Microtus pennsylvanicus), ten woodchucks (Marmota monax), thirteen grey squirrels (Sciurus carolinensis), thirteen ring-billed gulls (Larus delawarensis), six red-tailed hawks (Buteo jamaicensis) and eight great horned owls (Bubo virginianus) received vaccinia virus recombinant expressing the rabies virus glycoprotein (V-RG) by direct instillation into the oral cavity. Each of ten coyotes (Canis latrans) received the virus in two vaccine-laden baits. Several voles and most of the gulls died from diseases unrelated to vaccination during the observation period, but all other animals remained healthy and survived. These deaths from causes other than vaccination and the absence of any lesions suggestive of vaccinia infection indicate that it is unlikely that any animal suffered or died as a result of V-RG administration. In addition several animals showed an unexpected high level of rabies neutralizing antibodies. PMID:2249183

Artois, M; Charlton, K M; Tolson, N D; Casey, G A; Knowles, M K; Campbell, J B

1990-10-01

56

Vaccinia recombinant virus expressing the rabies virus glycoprotein: safety and efficacy trials in Canadian wildlife.  

PubMed Central

Twenty-six meadow voles (Microtus pennsylvanicus), ten woodchucks (Marmota monax), thirteen grey squirrels (Sciurus carolinensis), thirteen ring-billed gulls (Larus delawarensis), six red-tailed hawks (Buteo jamaicensis) and eight great horned owls (Bubo virginianus) received vaccinia virus recombinant expressing the rabies virus glycoprotein (V-RG) by direct instillation into the oral cavity. Each of ten coyotes (Canis latrans) received the virus in two vaccine-laden baits. Several voles and most of the gulls died from diseases unrelated to vaccination during the observation period, but all other animals remained healthy and survived. These deaths from causes other than vaccination and the absence of any lesions suggestive of vaccinia infection indicate that it is unlikely that any animal suffered or died as a result of V-RG administration. In addition several animals showed an unexpected high level of rabies neutralizing antibodies. PMID:2249183

Artois, M; Charlton, K M; Tolson, N D; Casey, G A; Knowles, M K; Campbell, J B

1990-01-01

57

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

Microsoft Academic Search

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 small- pox 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

David R. Kaufman; Jaap Goudsmit; Lennart Holterman; Bonnie A. Ewald; Matthew Denholtz; Colleen Devoy; Ayush Giri; Lauren E. Grandpre; Jean-Michel Heraud; Genoveffa Franchini; Michael S. Seaman; Menzo J. E. Havenga; Dan H. Barouch

2008-01-01

58

Potential effect of prior raccoonpox virus infection in raccoons on vaccinia-based rabies immunization  

Microsoft Academic Search

BACKGROUND: The USDA, Wildlife Services cooperative oral rabies vaccination (ORV) program uses a live vaccinia virus-vectored (genus Orthopoxvirus) vaccine, Raboral V-RG® (V-RG), to vaccinate specific wildlife species against rabies virus in several regions of the U.S. Several naturally occurring orthopoxviruses have been found in North America, including one isolated from asymptomatic raccoons (Procyon lotor). The effect of naturally occurring antibodies

J Jeffrey Root; Robert G McLean; Dennis Slate; Kathleen A MacCarthy; Jorge E Osorio

2008-01-01

59

Isolation and characterization of cidofovir resistant vaccinia viruses  

PubMed Central

Background The emergence of drug resistant viruses, together with the possibility of increased virulence, is an important concern in the development of new antiviral compounds. Cidofovir (CDV) is a phosphonate nucleotide that is approved for use against cytomegalovirus retinitis and for the emergency treatment of smallpox or complications following vaccination. One mode of action for CDV has been demonstrated to be the inhibition of the viral DNA polymerase. Results We have isolated several CDV resistant (CDVR) vaccinia viruses through a one step process, two of which have unique single mutations within the DNA polymerase. An additional resistant virus isolate provides evidence of a second site mutation within the genome involved in CDV resistance. The CDVR viruses were 3–7 fold more resistant to the drug than the parental viruses. The virulence of the CDVR viruses was tested in mice inoculated intranasally and all were found to be attenuated. Conclusion Resistance to CDV in vaccinia virus can be conferred individually by at least two different mutations within the DNA polymerase gene. Additional genes may be involved. This one step approach for isolating resistant viruses without serial passage and in the presence of low doses of drug minimizes unintended secondary mutations and is applicable to other potential antiviral agents. PMID:18479513

Becker, Marie N; Obraztsova, Maria; Kern, Earl R; Quenelle, Debra C; Keith, Kathy A; Prichard, Mark N; Luo, Ming; Moyer, Richard W

2008-01-01

60

Interaction between Rabies Infection and Oral Administration of Vaccinia-Rabies Recombinant Virus to Foxes (Vulpes vulpes)  

Microsoft Academic Search

SUMMARY We have investigated the influence of anti-rabies vaccination on the onset of the disease as well as the delay of death in foxes previously infected with rabies virus. A live vaccinia recombinant virus expressing the rabies virus glycoprotein (VVTGgRAB) was used as vaccine. Foxes were divided into six experimental groups of four animals. On day 0, each fox was

B. M. Brochier; J. Blancou; M. F. A. Aubert; M. P. Kieny; P. Desmettre; P.-P. Pastoret

1989-01-01

61

Comparison of the susceptibility of the red fox ( Vulpes vulpes) to a vaccinia-rabies recombinant virus and to cowpox virus  

Microsoft Academic Search

Sylvatic rabies can be efficiently controlled by vaccination of foxes with a vaccinia-rabies recombinant virus. However, the risk of recombination between the engineered vaccine virus and other orthopoxviruses endemic in wildlife, such as cowpox virus, still needs to be investigated. In this study, foxes inoculated orally and intradermally with cowpox virus were found to be not very susceptible to cowpox

D. Boulanger; B. Brochier; A. Crouch; M. Bennett; R. M. Gaskell; D. Baxby; P.-P. Pastoret

1995-01-01

62

Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.  

PubMed

CDC and the U.S. Food and Drug Administration rely on state and local health departments, health-care providers, and the public to report the occurrence of adverse events after vaccination to the Vaccine Adverse Event Reporting System. With such data, trends can be accurately monitored, unusual occurrences of adverse events can be detected, and the safety of vaccination intervention activities can be evaluated. On January 24, 2003, the U.S. Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a biologic terrorism event. As part of the DHHS Smallpox Preparedness and Response Program, CDC in consultation with experts, established surveillance case definitions for adverse events after smallpox vaccination. Adverse reactions after smallpox vaccination identified during the 1960s surveillance activities were classified on the basis of clinical description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia; accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia; erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and pyogenic infection of the vaccination site. This report provides uniform criteria used for the surveillance case definition and classification for these previously recognized adverse reactions used during the DHHS Smallpox Preparedness and Response Program. Inadvertent inoculation was changed to more precisely describe this event as inadvertent autoinoculation and contact transmission, nonocular and ocular vaccinia. Pyogenic infection also was renamed superinfection of the vaccination site or regional lymph nodes. Finally, case definitions were developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac adverse event (dilated cardiomyopathy) and are included in this report. The smallpox vaccine surveillance case definitions presented in the report can be used in future vaccination programs to ensure uniform reporting guidelines and case classification. PMID:16456528

Casey, Christine; Vellozzi, Claudia; Mootrey, Gina T; Chapman, Louisa E; McCauley, Mary; Roper, Martha H; Damon, Inger; Swerdlow, David L

2006-02-01

63

Susceptibility of Vaccinia Virus to Chemical Disinfectants  

PubMed Central

Vaccinia virus (VACV) is the cause of bovine vaccinia (BV), an emerging zoonotic disease that affects dairy cows and milkers. Some chemical disinfectants have been used on farms affected by BV to disinfect cow teats and milkers' hands. To date, there is no information about the efficacy of disinfectants against VACV. Therefore, this study aimed to assess the virucidal activity of some active disinfectants commonly used in the field. Sodium hypochlorite, quaternary ammonium combined with chlorhexidine, and quaternary ammonium combined with glutaraldehyde were effective in inactivating the virus at all concentrations tested. Iodine and quaternary ammonium as the only active component were partially effective. The presence of bovine feces as organic matter and light decreased the effectiveness of sodium hypochlorite. These results show that an appropriated disinfection and asepsis of teats and hands may be helpful in the control and prevention of BV and other infections with VACV. PMID:21734141

de Oliveira, Tércia Moreira Ludolfo; Rehfeld, Izabelle Silva; Coelho Guedes, Maria Isabel Maldonado; Ferreira, Jaqueline Maria Siqueira; Kroon, Erna Geessien; Lobato, Zélia Inęs Portela

2011-01-01

64

FIRST NORTH AMERICAN FIELD RELEASE OF A VACCINIA-RABIES GLYCOPROTEIN RECOMBINANT VIRUS  

Microsoft Academic Search

Following nearly 10 ?T of extensive laboratory evaluation, a vaccinia-rabies glycopro- tein (V-RG) vaccine was the first recombinant virus to undergo limited North American field release on 20 August 1990. The free-ranging raccoon population on Parramore Island (Virginia, USA) was exposed to a high density (10 baits\\/ha) of vaccine-laden baits distributed on a 300 ha vaccination area. An annual total

Cathleen A. Hanlon; Michael Niezgoda; Amir N. Hamir; Carolin Schumacher; Hilary Koprowski; Charles E. Rupprecht

65

Safety and Tolerability of Conserved Region Vaccines Vectored by Plasmid DNA, Simian Adenovirus and Modified Vaccinia Virus Ankara Administered to Human Immunodeficiency Virus Type 1-Uninfected Adults in a Randomized, Single-Blind Phase I Trial  

PubMed Central

Trial Design HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee) adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported. Methods Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination. Results Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1) and predominantly transient (<48 hours). Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range) of 633 (231-1533) post-vaccination, which is of no safety concern. Conclusions These data demonstrate safety and good tolerability of the pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines and together with their high immunogenicity support their further development towards efficacy studies. Trial Registration ClinicalTrials.gov NCT01151319 PMID:25007091

Hayton, Emma-Jo; Rose, Annie; Ibrahimsa, Umar; Del Sorbo, Mariarosaria; Capone, Stefania; Crook, Alison; Black, Antony P.; Dorrell, Lucy; Hanke, Tomas

2014-01-01

66

Vaccinia Virus Requires Glutamine but Not Glucose for Efficient Replication  

PubMed Central

ABSTRACT Viruses require host cell metabolism to provide the necessary energy and biosynthetic precursors for successful viral replication. Vaccinia virus (VACV) is a member of the Poxviridae family, and its use as a vaccine enabled the eradication of variola virus, the etiologic agent of smallpox. A global metabolic screen of VACV-infected primary human foreskin fibroblasts suggested that glutamine metabolism is altered during infection. Glutamine and glucose represent the two main carbon sources for mammalian cells. Depriving VACV-infected cells of exogenous glutamine led to a substantial decrease in infectious virus production, whereas starving infected cells of exogenous glucose had no significant impact on replication. Viral yield in glutamine-deprived cells or in cells treated with an inhibitor of glutaminolysis, the pathway of glutamine catabolism, could be rescued by the addition of multiple tricarboxylic acid (TCA) cycle intermediates. Thus, VACV infection induces a metabolic alteration to fully rely on glutamine to anaplerotically maintain the TCA cycle. VACV protein synthesis, but not viral transcription, was decreased in glutamine-deprived cells, which corresponded with a dramatic reduction in all VACV morphogenetic intermediates. This study reveals the unique carbon utilization program implemented during poxvirus infection and provides a potential metabolic pathway to target viral replication. IMPORTANCE Viruses are dependent on the metabolic machinery of the host cell to supply the energy and molecular building blocks needed for critical processes including genome replication, viral protein synthesis, and membrane production. This study investigates how vaccinia virus (VACV) infection alters global cellular metabolism, providing the first metabolomic analysis for a member of the poxvirus family. Unlike most viruses examined to date, VACV does not activate glycolysis, and exogenous glucose is not required for maximal virus production. Instead, VACV requires exogenous glutamine for efficient replication, and inhibition of glutamine metabolism effectively blocks VACV protein synthesis. This study defines a major metabolic perturbation essential for the replication of a poxvirus and may lead to the discovery of novel antiviral therapies based on metabolic inhibitors. PMID:24501408

Fontaine, Krystal A.; Camarda, Roman

2014-01-01

67

Identification and analysis of vaccinia virus palmitylproteins.  

PubMed

Vaccinia virus encodes at least eight proteins that incorporate label from tritiated palmitic acid when it is added to infected cell cultures. Three of these palmitylproteins are encoded by the A33R, B5R, and F13L open reading frames and migrate by gel electrophoresis with relative molecular masses of 23-28, 42, and 37 kDa, respectively. In this report we provide evidence that the A22R and A36R open reading frames also encode palmitylproteins with apparent molecular masses of 22 and 50-55 kDa, respectively. Furthermore, the hemagglutinin protein (A56R) from the Copenhagen strain is shown to be palmitylated while the hemagglutinin protein from the WR and IHD-J strains is not. A 94-kDa VV palmitylprotein appears to be a multimeric complex composed of the B5R protein and possibly others. All vaccinia-encoded palmitylproteins are present in the membranous fraction of cells and are specific for the trans-Golgi network membrane-enveloped forms of the virus, suggesting that these proteins play a role in the envelopment and egress of virions or the infectivity of released virus. PMID:11017799

Grosenbach, D W; Hansen, S G; Hruby, D E

2000-09-15

68

Development of a novel, guinea pig-specific IFN-? ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine.  

PubMed

The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-? was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-? ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model. PMID:24856783

Gillis, Peter A; Hernandez-Alvarado, Nelmary; Gnanandarajah, Josephine S; Wussow, Felix; Diamond, Don J; Schleiss, Mark R

2014-06-30

69

Vaccinia Virus Recombinant Expressing Herpes Simplex Virus Type 1 Glycoprotein D Prevents Latent Herpes in Mice  

NASA Astrophysics Data System (ADS)

In humans, herpes simplex virus causes a primary infection and then often a latent ganglionic infection that persists for life. Because these latent infections can recur periodically, vaccines are needed that can protect against both primary and latent herpes simplex infections. Infectious vaccinia virus recombinants that contain the herpes simplex virus type 1 (HSV-1) glycoprotein D gene under control of defined early or late vaccinia virus promoters were constructed. Tissue culture cells infected with these recombinant viruses synthesized a glycosylated protein that had the same mass (60,000 daltons) as the glycoprotein D produced by HSV-1. Immunization of mice with one of these recombinant viruses by intradermal, subcutaneous, or intraperitoneal routes resulted in the production of antibodies that neutralized HSV-1 and protected the mice against subsequent lethal challenge with HSV-1 or HSV-2. Immunization with the recombinant virus also protected the majority of the mice against the development of a latent HSV-1 infection of the trigeminal ganglia. This is the first demonstration that a genetically engineered vaccine can prevent the development of latency.

Cremer, Kenneth J.; Mackett, Michael; Wohlenberg, Charles; Notkins, Abner Louis; Moss, Bernard

1985-05-01

70

Contact transmission of vaccinia virus from smallpox vaccinees in the United States, 2003-2011.  

PubMed

Since 2002, approximately 40,000 US civilians and 2.1 million military personnel have been vaccinated against smallpox. The vaccine contains live vaccinia virus that can be transferred through physical contact. This report summarizes numbers, rates, and characteristics of contact vaccinia cases that presented between December 2002 and March 2011. Cases were identified from reports in adverse event reporting systems and peer-reviewed literature. One hundred fifteen cases of vaccinia transmission through contact were identified (5.4 per 100,000 vaccinees); 52 reports (45%) noted laboratory confirmation. Three-quarters of vaccinees, but fewer than 8% of contact vaccinia cases, were described as military members. Most cases were household or intimate contacts (n=86, 75%) or wrestling partners (n=18, 16%) of vaccinees. Nearly all cases manifested mild, local skin reactions; of 14 hospitalized cases, one was life-threatening. Vaccinia transmission from vaccinees is relatively infrequent. Continued attention to both vaccinee education and screening for contraindications to vaccination is appropriate. PMID:22192851

Wertheimer, Ellen R; Olive, Denise S; Brundage, John F; Clark, Leslie L

2012-02-01

71

Oral vaccination of raccoons ( Procyon lotor) with genetically modified rabies virus vaccines  

Microsoft Academic Search

Oral vaccination is an important tool currently in use to control the spread of rabies in wildlife populations in various programs around the world. Oral rabies vaccination (ORV) of raccoons represents the largest targeted program to control wildlife rabies in the United States. Currently, the vaccinia-rabies glycoprotein recombinant virus vaccine (V-RG) is the only licensed oral rabies vaccine in the

Jesse D. Blanton; Joshua Self; Michael Niezgoda; Marie-Luise Faber; Bernhard Dietzschold; Charles Rupprecht

2007-01-01

72

Pathogeneses of respiratory infections with virulent and attenuated vaccinia viruses  

Microsoft Academic Search

BACKGROUND: Respiratory infection with the neurovirulent vaccinia virus (VV) strain Western Reserve (WR) results in an acute infection of the lung followed by dissemination of the virus to other organs and causes lethality in mice. The mechanisms of lethality are not well-understood. In this study, we analyzed virus replication and host immune responses after intranasal infection with lethal and non-lethal

Daisuke Hayasaka; Francis A Ennis; Masanori Terajima

2007-01-01

73

Development of a highly efficacious vaccinia-based dual vaccine against smallpox and anthrax, two important bioterror entities.  

PubMed

Bioterrorism poses a daunting challenge to global security and public health in the 21st century. Variola major virus, the etiological agent of smallpox, and Bacillus anthracis, the bacterial pathogen responsible for anthrax, remain at the apex of potential pathogens that could be used in a bioterror attack to inflict mass casualties. Although licensed vaccines are available for both smallpox and anthrax, because of inadequacies associated with each of these vaccines, serious concerns remain as to the deployability of these vaccines, especially in the aftermath of a bioterror attack involving these pathogens. We have developed a single vaccine (Wyeth/IL-15/PA) using the licensed Wyeth smallpox vaccine strain that is efficacious against both smallpox and anthrax due to the integration of immune-enhancing cytokine IL-15 and the protective antigen (PA) of B. anthracis into the Wyeth vaccinia virus. Integration of IL-15 renders Wyeth vaccinia avirulent in immunodeficient mice and enhances anti-vaccinia immune responses. Wyeth/IL-15/PA conferred sterile protection against a lethal challenge of B. anthracis Ames strain spores in rabbits. A single dose of Wyeth/IL-15/PA protected 33% of the vaccinated A/J mice against a lethal spore challenge 72 h later whereas a single dose of licensed anthrax vaccine protected only 10%. Our dual vaccine Wyeth/IL-15/PA remedies the inadequacies associated with the licensed vaccines, and the inherent ability of Wyeth vaccinia virus to be lyophilized without loss of potency makes it cold-chain independent, thus simplifying the logistics of storage, stockpiling, and field delivery in the event of a bioterror attack involving smallpox or anthrax. PMID:20921397

Merkel, Tod J; Perera, Pin-Yu; Kelly, Vanessa K; Verma, Anita; Llewellyn, Zara N; Waldmann, Thomas A; Mosca, Joseph D; Perera, Liyanage P

2010-10-19

74

Newcastle disease virus f glycoprotein expressed from a recombinant vaccinia virus vector protects chickens against live?virus challenge  

Microsoft Academic Search

Chickens were immunised using a vaccinia recombinant virus (vaccinia?Italien?F), expressing the F protein of Newcastle disease virus (NDV). Immunisation was successful using either TK” cells infected with the vaccinia?Italien?F virus, the recombinant virus grown in TK7 cells and inoculated intra?cerebrally in one?day?old chickens or the recombinant virus given by wing?web to adult chickens after adaptation by alternate passage in chick

G. Meulemans; C. Letellier; M. Gonze; M. C. Carlier; A. Burny

1988-01-01

75

Glycosylated and nonglycosylated complement control protein of the lister strain of vaccinia virus.  

PubMed

The vaccinia virus complement control protein (VCP) is a secreted viral protein that binds the C3b and C4b complement components and inhibits the classic and alternative complement pathways. Previously, we reported that an attenuated smallpox vaccine, LC16m8, which was derived from the Lister strain of vaccinia virus (VV-Lister), expressed a glycosylated form of VCP, whereas published sequence data at that time indicated that the VV-Lister VCP has no motif for N-linked glycosylation. We were interested in determining whether the glycosylation of VCP impairs its biological activity, possibly contributing to the attenuation of LC16m8, and the likely origin of the glycosylated VCP. Expression analysis indicated that VV-Lister contains substrains expressing glycosylated VCP and substrains expressing nonglycosylated VCP. Other strains of smallpox vaccine, as well as laboratory strains of vaccinia virus, all expressed nonglycosylated VCP. Individual Lister virus clones expressing either the glycosylated VCP or the nonglycosylated species were isolated, and partially purified VCP from the isolates were found to be functional equivalents in binding human C3b and C4b complement proteins and inhibiting hemolysis and in immunogenicity. Recombinant vaccinia viruses expressing FLAG-tagged glycosylated VCP (FLAG-VCPg) and nonglycosylated VCP (FLAG-VCP) were constructed based on the Western Reserve strain. Purified FLAG-VCP and FLAG-VCPg bind human C3b and C4b and blocked complement-mediated hemolysis. Our data suggest that glycosylation did not affect the biological activity of VCP and thus may not have contributed to the attenuation of LC16m8. In addition, the LC16m8 virus likely originated from a substrain of VV-Lister that expresses glycosylated VCP. PMID:25030055

Meseda, Clement A; Kuhn, Jordan; Atukorale, Vajini; Campbell, Joseph; Weir, Jerry P

2014-09-01

76

Vaccinia Virus Induces Rapid Necrosis in Keratinocytes by a STAT3-Dependent Mechanism  

PubMed Central

Rationale Humans with a dominant negative mutation in STAT3 are susceptible to severe skin infections, suggesting an essential role for STAT3 signaling in defense against cutaneous pathogens. Methods To focus on innate antiviral defenses in keratinocytes, we used a standard model of cutaneous infection of severe combined immunodeficient mice with the current smallpox vaccine, ACAM-2000. In parallel, early events post-infection with the smallpox vaccine ACAM-2000 were investigated in cultured keratinocytes of human and mouse origin. Results Mice treated topically with a STAT3 inhibitor (Stattic) developed larger vaccinia lesions with higher virus titers and died more rapidly than untreated controls. Cultured human and murine keratinocytes infected with ACAM-2000 underwent rapid necrosis, but when treated with Stattic or with inhibitors of RIP1 kinase or caspase-1, they survived longer, produced higher titers of virus, and showed reduced activation of type I interferon responses and inflammatory cytokines release. Treatment with inhibitors of RIP1 kinase and STAT3, but not caspase-1, also reduced the inflammatory response of keratinocytes to TLR ligands. Vaccinia growth properties in Vero cells, which are known to be defective in some antiviral responses, were unaffected by inhibition of RIP1K, caspase-1, or STAT3. Conclusions Our findings indicate that keratinocytes suppress the replication and spread of vaccinia virus by undergoing rapid programmed cell death, in a process requiring STAT3. These data offer a new framework for understanding susceptibility to skin infection in patients with STAT3 mutations. Interventions which promote prompt necroptosis/pyroptosis of infected keratinocytes may reduce risks associated with vaccination with live vaccinia virus. PMID:25419841

He, Yong; Fisher, Robert; Chowdhury, Soma; Sultana, Ishrat; Pereira, Claudia P.; Bray, Mike; Reed, Jennifer L.

2014-01-01

77

Vaccinia Virus Induces Programmed Necrosis in Ovarian Cancer Cells  

PubMed Central

The mechanisms by which oncolytic vaccinia virus induces tumor cell death are poorly understood. We have evaluated cell death pathways following infection of ovarian cancer cells with both wild-type and thymidine kinase-deleted (dTK) Lister strain vaccinia. We show that death does not rely upon classical apoptosis despite the appearances of some limited apoptotic features, including phosphatidylserine externalization and appearance of sub-G1 DNA populations. Vaccinia infection induces marked lipidation of LC3 proteins, but there is no general activation of the autophagic process and cell death does not rely upon autophagy induction. We show that vaccinia induces necrotic morphology on transmission electron microscopy, accompanied by marked by reductions in intracellular adenosine triphosphate, altered mitochondrial metabolism, and release of high mobility group box 1 (HMGB1) protein. This necrotic cell death appears regulated, as infection induces formation of a receptor interacting protein (RIP1)/caspase-8 complex. In addition, pharmacological inhibition of both RIP1 and substrates downstream of RIP1, including MLKL, significantly attenuate cell death. Blockade of TNF-?, however, does not alter virus efficacy, suggesting that necrosis does not result from autocrine cytokine release. Overall, these results show that, in ovarian cancer cells, vaccinia virus causes necrotic cell death that is mediated through a programmed series of events. PMID:23985697

Whilding, Lynsey M; Archibald, Kyra M; Kulbe, Hagen; Balkwill, Frances R; Oberg, Daniel; McNeish, Iain A

2013-01-01

78

Potential effect of prior raccoonpox virus infection in raccoons on vaccinia-based rabies immunization  

PubMed Central

Background The USDA, Wildlife Services cooperative oral rabies vaccination (ORV) program uses a live vaccinia virus-vectored (genus Orthopoxvirus) vaccine, Raboral V-RG® (V-RG), to vaccinate specific wildlife species against rabies virus in several regions of the U.S. Several naturally occurring orthopoxviruses have been found in North America, including one isolated from asymptomatic raccoons (Procyon lotor). The effect of naturally occurring antibodies to orthopoxviruses on successful V-RG vaccination in raccoons is the focus of this study. Results Overall, raccoons pre-immunized (n = 10) with a recombinant raccoonpox virus vaccine (RCN-F1) responded to vaccination with V-RG with lower rabies virus neutralizing antibody (VNA) titers than those which were not pre-immunized (n = 10) and some failed to seroconvert for rabies VNA to detectable levels. Conclusion These results suggest that the success of some ORV campaigns may be hindered where raccoonpox virus or possibly other orthopoxvirus antibodies are common in wildlife species targeted for ORV. If these areas are identified, different vaccination strategies may be warranted. PMID:18834520

Root, J Jeffrey; McLean, Robert G; Slate, Dennis; MacCarthy, Kathleen A; Osorio, Jorge E

2008-01-01

79

Recombinant Vaccinia Virus Expressing the Herpes Simplex Virus Type 1 Glycoprotein C Protects Mice against Herpes Simplex Virus Challenge  

Microsoft Academic Search

SUMMARY The gene encoding the herpes simplex virus type I (HSV-1) glycoprotein C (gC) was isolated and cloned into a vaccinia virus insertion vector, and the resulting vaccinia-gC vector was used to construct a recombinant vaccinia virus that expressed gC (VVgC5). Infection of cells with VVgC5 resulted in cell surface expression of authentic HSV-1 gC. HSV-1 gC-specific neutralizing antibodies were

JERRY P. WEIR; MALCOLM BENNETT; ELIZABETH M. ALLEN; KAREN L. ELKINS; STEPHEN MARTIN; BARRY T. ROUSE

1989-01-01

80

Emergence and reemergence of vaccinia-like viruses: global scenario and perspectives.  

PubMed

Among the members of the genus Orthopoxvirus (OPXV), vaccinia virus (VACV), the type species of the genus is a double-stranded DNA virus, belongs to the subfamily Chordopoxvirinae of the family Poxviridae. The causative agents of smallpox, VACV and Variola virus are mutually immunogenic and the type species of Orthopoxvirus, cause only mild complications in humans. Therefore, the VACV was used as a smallpox vaccine world over under mass immunization program promoted by World Health Organization, which lead to the variola eradication globally in 1979. Since then, no vaccination of human population has been carried out; however, vaccination has been continued for at-risk laboratory workers, military personnel and others working with recombinant VACV or other non-variola orthopoxviruses (OPXVs). There has now been a surge in the development of safer smallpox vaccines and understanding of the biology of VACV necessitating re-use of this vaccine in most vulnerable population, because of rise in bioterrorist threats globally. Also, globally there has been the emergence and re-emergence of vaccinia-like viruses (VLVs) in Brazil, buffalopox viruses in Egypt, Indonesia, India and its neighbouring countries like Nepal, Pakistan. Bioterrorism as well as emergence and re-emergence of the VLVs constitute a concern as 50 % of the population globally (40 % in USA) <30 years are unvaccinated and most vulnerable for smallpox reemergence. Thus, the search for new generation safer smallpox vaccine entails review of biology of VLVs in the smallpox-free world. In this review, we present occurrence of VLVs in the world with exhaustive discussion particularly on the emergence and re-emergence of these viruses in India and Brazil where VLVs are sufficiently studied. PMID:23729995

Singh, R K; Balamurugan, V; Bhanuprakash, V; Venkatesan, G; Hosamani, M

2012-06-01

81

Characterization of UVC Light Sensitivity of Vaccinia Virus  

Microsoft Academic Search

J\\/m2, three relative humidity (RH) levels (20%, 60%, and 80%), and suspensions of virus in either water or synthetic respiratory fluid. Dose-response plots show that vaccinia virus susceptibility increased with decreas- ing RH. These plots also show a significant nonlinear component and a poor fit when using a first-order decay model but show a reasonable fit when we assume that

James J. McDevitt; Ka Man Lai; Stephen N. Rudnick; E. Andres Houseman; Melvin W. First; Donald K. Milton

2007-01-01

82

Comparison of the replication characteristics of vaccinia virus strains Guang 9 and Tian Tan in vivo and in vitro.  

PubMed

Vaccinia virus is widely used as a vector in the development of recombinant vaccines. Vaccinia virus strain Guang 9 (VG9), which was derived from vaccinia virus strain Tian Tan (VTT) by successive plaque-cloning purification, was more attenuated than VTT. In this study, the host cell range and the growth and replication of VG9 were compared with those of VTT. The results showed that both VG9 and VTT could infect permissive cells (Vero, TK-143 and CEF) and semipermissive cells PK (15) and induced a visible cytopathic effect (CPE). Both strains could infect nonpermissive CHO-K1 cells but neither was able to reproduce. The replicative ability of VG9 was a little lower than that of VTT. Additionally, recombinant vaccinia viruses containing a firefly luciferase gene (VG9-L and VTT-L) were constructed, and their expression in vitro and replication and spread in vivo were compared. The expression ability of VG9-L was lower than that of VTT-L. Whole-animal imaging data indicated that VG9-L could reproduce quickly and express the exogenous protein at the site of inoculation, regardless of whether the intramuscular, intracutaneous, subcutaneous or celiac inoculation route was used. VG9-L was better in its ability to express a foreign protein than VTT-L, but the time during which expression occurred was shorter. There was no dissemination of virus in mice inoculated with either strain. In summary, this study demonstrates the possibility of using VG9 for the production of smallpox vaccines or the construction of recombinant vaccinia virus vaccines. PMID:24838849

Zhu, Rong; Liu, Qiang; Huang, Weijin; Yu, Yongxin; Wang, Youchun

2014-10-01

83

Vaccinia virus induces cellular mRNA degradation.  

PubMed Central

The infection of mouse L cells with vaccinia virus induced a rapid inhibition of cellular polypeptide synthesis and a diversion of protein synthesis to the exclusive production of viral polypeptides. This shutoff of cell-specific protein synthesis was achieved by a novel mechanism by which the virus induced the rapid degradation of cellular mRNAs. Concurrent with the degradation of cellular mRNA, the virus proceeds in the orderly temporal expression of its own genetic information. The effect of vaccinia virus infection upon two abundant L-cell mRNAs was assessed by using the highly conserved cDNA sequences that encode chicken beta-actin and rat alpha-tubulin. Hybridization analyses demonstrated that throughout infection there is a rapid and progressive degradation of both of these mRNAs. In fact, after 3 h of infection they are reduced to less than 50% of their concentration in uninfected L cells, and between 8 to 10 h they are almost entirely degraded. This observation explains in part the mechanism by which vaccinia virus inhibits host cell protein synthesis. Images PMID:6620463

Rice, A P; Roberts, B E

1983-01-01

84

Enhancement of vaccinia vaccine potency by linkage of tumor antigen gene to gene encoding calreticulin  

Microsoft Academic Search

Vaccinia vaccines have become important vectors for antigen-specific immunotherapy. Calreticulin has been shown to enhance MHC class I presentation of linked peptide\\/protein and may be useful for antigen-specific cancer treatment. An innovative vaccine administering antigen linked to calreticulin via a vaccinia vector may generate a potent antigen-specific antitumor response. We tested the efficacy of linking calreticulin (CRT) to model antigen

Chia-Jung Hsieh; Tae Woo Kim; Chien-Fu Hung; Jeremy Juang; Michelle Moniz; David A. K. Boyd; Liangmei He; Pei-Jer Chen; Chien-Hung Chen; T.-C. Wu

2004-01-01

85

A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine.  

PubMed

Data from successful attenuated lentiviral vaccine studies indicate that fully mature Env-specific antibodies characterized by high titer, high avidity, and the predominant recognition of conformational epitopes are associated with protective efficacy. Although vaccination with a DNA prime/recombinant vaccinia-vectored vaccine boost strategy has been found to be effective in some trials with non-human primate/simian/human immunodeficiency virus (SHIV) models, it remains unclear whether this vaccination strategy could elicit mature equine infectious anemia virus (EIAV) Env-specific antibodies, thus protecting vaccinated horses against EIAV infection. Therefore, in this pilot study we vaccinated horses using a strategy based on DNA prime/recombinant Tiantan vaccinia (rTTV)-vectored vaccines encoding EIAV env and gag genes, and observed the development of Env-specific antibodies, neutralizing antibodies, and p26-specific antibodies. Vaccination with DNA induced low titer, low avidity, and the predominant recognition of linear epitopes by Env-specific antibodies, which was enhanced by boosting vaccinations with rTTV vaccines. However, the maturation levels of Env-specific antibodies induced by the DNA/rTTV vaccines were significantly lower than those induced by the attenuated vaccine EIAV(FDDV). Additionally, DNA/rTTV vaccines did not elicit broadly neutralizing antibodies. After challenge with a virulent EIAV strain, all of the vaccinees and control horses died from EIAV disease. These data indicate that the regimen of DNA prime/rTTV vaccine boost did not induce mature Env-specific antibodies, which might have contributed to immune protection failure. PMID:23171359

Meng, Qinglai; Lin, Yuezhi; Ma, Jian; Ma, Yan; Zhao, Liping; Li, Shenwei; Yang, Kai; Zhou, Jianhua; Shen, Rongxian; Zhang, Xiaoyan; Shao, Yiming

2012-12-01

86

Human immunodeficiency virus-like particles produced by a vaccinia virus expression vector.  

PubMed Central

Infectious retrovirus particles consist of a core structure containing RNA and gag-pol polypeptides surrounded by a lipid membrane studded with env proteins. A recombinant vaccinia virus was designed to express the entire gag-pol precursor protein of the human immunodeficiency virus type 1. Synthesis and processing of gag proteins occurred in mammalian cells infected with this live recombinant virus, and reverse transcriptase was detected largely in the medium. Electron micrographs revealed immature retrovirus-like particles budding from the plasma membrane and extracellular particles with morphological characteristics of immature and mature human immunodeficiency virus. The latter contained functional reverse transcriptase as well as processed p24 and p17 gag polypeptides. Thus, assembly and maturation of human immunodeficiency virus-like particles can occur in the absence of either infectious RNA molecules or env proteins. The production of noninfectious virus-like particles by expression vectors should be useful for biochemical studies and could provide a safe source of material for the development of vaccines. Images PMID:2479031

Karacostas, V; Nagashima, K; Gonda, M A; Moss, B

1989-01-01

87

Vaccinia Virus Penetration Requires Cholesterol and Results in Specific Viral Envelope Proteins Associated with Lipid Rafts  

Microsoft Academic Search

Vaccinia virus infects a wide variety of mammalian cells from different hosts, but the mechanism of virus entry is not clearly defined. The mature intracellular vaccinia virus contains several envelope proteins medi- ating virion adsorption to cell surface glycosaminoglycans; however, it is not known how the bound virions initiate virion penetration into cells. For this study, we investigated the importance

Che-Sheng Chung; Cheng-Yen Huang; Wen Chang

2005-01-01

88

Vaccinia virus growth factor stimulates tyrosine protein kinase activity of A431 cell epidermal growth factor receptors.  

PubMed Central

Infection of A431 cells with vaccinia virus, or exposure to a mitogenic polypeptide secreted by vaccinia virus-infected cells, induces tyrosine phosphorylation of epidermal growth factor receptors. Images PMID:2431267

King, C S; Cooper, J A; Moss, B; Twardzik, D R

1986-01-01

89

Vaccinia virus-induced smallpox postvaccinal encephalitis in case of blood-brain barrier damage.  

PubMed

Smallpox vaccination is the only currently effective mean to combat the threat of variola virus used as a bioterrorism agent, although it is responsible for a rare but serious complication, the postvaccinal encephalitis (PVE). Development of safer vaccines therefore is a high priority as the PVE physiopathology is not well understood to date. If vaccinia virus (VACV) is responsible for PVE by central nervous system (CNS) dissemination, trans-migration of the VACV across the blood-brain barrier (BBB) would be supposed to be essential. Given the complexity of the pathogenesis of vaccinia neurovirulence, an in vitro BBB model was used to explore the mechanism of VACV to induce BBB permeability. Two VACV strains were studied, the neurovirulent Western Reserve strain (VACV-WR) and the vaccine reference Lister strain (VACV-List). A mouse model was also developed to study the ability of these two viral strains to propagate in the brain from the blood compartment, their neurovirulence and their neuropathogenesis. In vitro, the loss of permeability resulted from the tight-junctions disruption was induced by virus replication. The ability of VACV to release infectious particles at the abluminal side suggests the capacity of both VACV strains to migrate across the BBB from the blood to the CNS. In vivo, the virus replication in mice CNS was strain-dependent. The VACV-WR laboratory strain proved to be neuroinvasive and neurovirulent, whereas the VACV-List strain is safe in physiological conditions. Mice PVE was observed only with VACV-WR in the co-infection model, when BBB opening was obtained by lipopolysaccharide (LPS) treatment. This study suggests that VACV is able to cross the BBB but encephalitis occurs only in the presence of a co-infection by bacteria. So, a model of co-infection, mimicked by LPS treatment, could have important implication towards the assessment of neurovirulence of new vaccines. PMID:22227123

Garcel, Aude; Fauquette, William; Dehouck, Marie-Pierre; Crance, Jean-Marc; Favier, Anne-Laure

2012-02-01

90

Antibodies against vaccinia virus do not neutralize extracellular enveloped virus but prevent virus release from infected cells and comet formation  

Microsoft Academic Search

Vaccinia virus (VV) produces two antigenically and structurally distinct infectious virions, intracellular mature virus (IMV) and extracellular enveloped virus (EEV). EEV is important for the efficient dissemi- nation of virus both in vivo and in vitro where it causes formation of comet-shaped virus plaques. Here, we show that EEV, in contrast to IMV, is resistant to neutralization by antibodies bound

Alain Vanderplasschen; Michael Hollinshead; Geoffrey L. Smith

1997-01-01

91

Field use of a vaccinia-rabies recombinant vaccine for the control of sylvatic rabies in Europe and North America.  

PubMed

During recent years, most research on the control of sylvatic rabies has concentrated on developing methods of oral vaccination of wild rabies vectors. To improve both the safety and the stability of the vaccine used, a recombinant vaccinia virus, which expresses the immunising glycoprotein of rabies virus (VRG), has been developed and tested extensively in the laboratory as well as in the field. From 1989 to 1995, approximately 8.5 million VRG vaccine doses were dispersed in Western Europe to vaccinate red foxes (Vulpes vulpes), and in the United States of America (USA) to vaccinate raccoons (Procyon lotor) and coyotes (Canis latrans). In Europe, the use of VRG has led to the elimination of sylvatic rabies from large areas of land, which have consequently been freed from the need for vaccination. Nevertheless, despite very good examples of cross-border cooperation, reinfections have occurred in some regions, due to the difficulty of co-ordinating vaccination plans among neighbouring countries. In the USA, preliminary data from field trails indicate a significant reduction in the incidence of rabies in vaccinated areas. PMID:9025144

Brochier, B; Aubert, M F; Pastoret, P P; Masson, E; Schon, J; Lombard, M; Chappuis, G; Languet, B; Desmettre, P

1996-09-01

92

Inhibitors of C5 Complement Enhance Vaccinia Virus Oncolysis  

PubMed Central

Genetically engineered tumor-selective vaccinia virus (VV) has been demonstrated to be a highly effective oncolytic agent, but immune clearance may limit its therapeutic potential. As previously demonstrated, immunosuppression can lead to significant enhancement of viral recovery and therapeutic effect, but the magnitude of complement-mediated viral inactivation has not been fully elucidated and warrants further investigation. Using fluorescent microscopy and quantitative plaque assays, we have determined complement's key role in viral clearance and its multi-faceted means to pathogen destruction. Complement can lead to direct viral destruction and inhibition of viral uptake into cells, even in the absence of anti-vaccinia antibodies. Our data demonstrate C5 to be integral to the clearance pathway, and its inhibition by Staphylococcal superantigen-like protein (SSL7) leads to a 90-fold and 150-fold enhancement of VV infectivity in both the presence and absence of anti-VV antibodies, respectively. This study suggests that complement inhibition may reduce vaccinia viral neutralization and may be critical to future in vivo work. PMID:23661042

Magge, Deepa; Guo, Z. Sheng; O'Malley, Mark E.; Francis, Lily; Ravindranathan, Roshni; Bartlett, David L.

2014-01-01

93

Efficacy and safety of a modified vaccinia Ankara (MVA) vectored plague vaccine in mice  

PubMed Central

The efficacy and safety of plague vaccines based on the modified vaccinia Ankara (MVA) viral vector was evaluated. MVA recombinants were constructed expressing Yersinia pestis antigens under the translational control of the encephalomyocarditis virus (EMCV) internal ribosomal entry site (IRES) and/or fused to the tissue plasminogen activator (tPA) secretory signal. A MVA/Y. pestis recombinant that expressed a truncated version of the low-calcium response V antigen (MVA/IRES/tPA/V307), conferred significant protection (87.5%–100%) against intranasal or intraperitoneal challenge with CO92 (encapsulated) or Java 9 (non-encapsulated) strains of Y pestis, respectively. In contrast, a MVA/Y. pestis recombinant that expressed the full-length V antigen provided only 37.5% protection against challenge with CO92 or Java 9 strains, respectively. Interestingly, a MVA/Y. pestis recombinant that expressed the capsular protein (F1) did not elicit significant antibody titers but still conferred 50% and 25% protection against CO92 or Java 9 challenge, respectively. The MVA/Y. pestis recombinant viruses did not demonstrate any mortality or morbidity in SCID mice. Based on their safety and efficacy in mice, these MVA/Y. pestis recombinants are candidates for further development as biodefense and public health vaccines. PMID:20638759

Brewoo, Joseph N.; Powell, Tim D.; Stinchcomb, Dan T.; Osorio, Jorge E.

2010-01-01

94

Immunogenicity and safety of the vaccinia virus LC16m8? vector expressing SIV Gag under a strong or moderate promoter in a recombinant BCG prime-recombinant vaccinia virus boost protocol.  

PubMed

We compared the effect of the very strong pSFJ1-10 and moderately strong p7.5 promoters on the immunogenicity and pathogenicity of the replication-competent vaccinia virus (VV) LC16m8? (m8?) vector harboring the SIV gag gene in a vaccination regimen consisting of a recombinant BCG-SIVGag (rBCG-SIVGag) prime followed by a recombinant vaccinia boost. m8?/pSFJ/SIVGag synthesized more Gag protein than m8?/p7.5/SIVGag but replicated less efficiently in vitro. In addition, m8?/pSFJ/SIVGag was less pathogenic and elicited Gag-specific IFN-?(+), CD107a(+), CD8(+) cells more efficiently than m8?/p7.5/SIVGag. Vaccination by this regimen elicited long-lasting Gag-specific CD8(+) T cells, the majority of which showed a CCR7(-) phenotype at over 8 weeks post-boost. Tetramer staining analyses revealed maintenance of Gag specific tetramer(+), CD62L(-), CD8(+) T cells for long time in vaccinated mice. However, Gag expression increased the neurotoxicity of the vaccinia vector, indicating the necessity of safety testing for each recombinant VV. We propose that this recombinant BCG prime-m8?/pSFJ/HIVGag boost regimen would be a promising vaccination procedure for preventing HIV infection. PMID:23731631

Sato, Hirotaka; Jing, Chen; Isshiki, Mao; Matsuo, Kazuhiro; Kidokoro, Minoru; Takamura, Shiki; Zhang, Xianfeng; Ohashi, Takashi; Shida, Hisatoshi

2013-08-01

95

Environmental Risk Assessment of Clinical Trials Involving Modified Vaccinia Virus Ankara (MVA)-Based Vectors  

PubMed Central

The modified vaccinia virus Ankara (MVA) strain, which has been developed as a vaccine against smallpox, is since the nineties widely tested in clinical trials as recombinant vector for vaccination or gene therapy applications. Although MVA is renowned for its safety, several biosafety aspects need to be considered when performing the risk assessment of a recombinant MVA (rMVA). This paper presents the biosafety issues and the main lessons learned from the evaluation of the clinical trials with rMVA performed in Belgium. Factors such as the specific characteristics of the rMVA, the inserted foreign sequences/transgene, its ability for reconversion, recombination and dissemination in the population and the environment are the main points of attention. Measures to prevent or manage identified risks are also discussed. PMID:24397528

Goossens, Martine; Pauwels, Katia; Willemarck, Nicolas; Breyer, Didier

2013-01-01

96

Generation of an attenuated Tiantan vaccinia virus by deletion of the ribonucleotide reductase large subunit.  

PubMed

Attenuation of the virulence of vaccinia Tiantan virus (VTT) underlies the strategy adopted for mass vaccination campaigns. This strategy provides advantages of safety and efficacy over traditional vaccines and is aimed at minimization of adverse health effects. In this study, a mutant form of the virus, MVTT was derived from VTT by deletion of the ribonucleotide reductase large subunit (R1) (TI4L). Compared to wild-type parental (VTT) and revertant (VTT-rev) viruses, virulence of the mutant MVTT was reduced by 100-fold based on body weight reduction and by 3,200-fold based on determination of the intracranial 50% lethal infectious dose. However, the immunogenicity of MVTT was equivalent to that of the parental VTT. We also demonstrated that the TI4L gene is not required for efficient replication. These data support the conclusion that MVTT can be used as a replicating virus vector or as a platform for the development of vaccines against infectious diseases and for cancer therapy. PMID:24677065

Kan, Shifu; Jia, Peng; Sun, Lili; Hu, Ningning; Li, Chang; Lu, Huijun; Tian, Mingyao; Qi, Yanxin; Jin, Ningyi; Li, Xiao

2014-09-01

97

Vaccinia virus hemagglutinin. A novel member of the immunoglobulin superfamily  

PubMed Central

Striking similarities between vaccinia virus hemagglutinin (VVHA) and proteins belonging to the Ig superfamily clearly indicate that VVHA, a 315-amino acid glycoprotein expressed on the surface of the infected cells, is a novel viral protein that can be added to the expanding list of the Ig superfamily. Its deduced amino acid sequence contains one Ig- like domain at the NH2 terminus, followed by two tandem repeating units and a hydrophobic region, suggestive of membrane spanning. The results offer an opportunity for the further study of the probable evolutionary and possible functional relationship between VVHA and other members of the Ig superfamily. Our observation, together with a recent finding that human CMV possibly encodes a protein similar to the MHC class I antigens (13), provides evidence supporting the fact that the viral capture of cellular Ig-related genes is more common than expected in vaccinia and other viruses, and that usage of an Ig-like domain as recognition signals might be extended from higher animals to animal viruses. PMID:2754392

1989-01-01

98

Genome Scale Patterns of Recombination between Coinfecting Vaccinia Viruses  

PubMed Central

ABSTRACT Recombination plays a critical role in virus evolution. It helps avoid genetic decline and creates novel phenotypes. This promotes survival, and genome sequencing suggests that recombination has facilitated the evolution of human pathogens, including orthopoxviruses such as variola virus. Recombination can also be used to map genes, but although recombinant poxviruses are easily produced in culture, classical attempts to map the vaccinia virus (VACV) genome this way met with little success. We have sequenced recombinants formed when VACV strains TianTan and Dryvax are crossed under different conditions. These were a single round of growth in coinfected cells, five rounds of sequential passage, or recombinants obtained using leporipoxvirus-mediated DNA reactivation. Our studies showed that recombinants contain a patchwork of DNA, with the number of exchanges increasing with passage. Further passage also selected for TianTan DNA and correlated with increased plaque size. The recombinants produced through a single round of coinfection contain a disproportionate number of short conversion tracks (<1 kbp) and exhibited 1 exchange per 12 kbp, close to the ?1 per 8 kbp in the literature. One by-product of this study was that rare mutations were also detected; VACV replication produces ?1 × 10?8 mutation per nucleotide copied per cycle of replication and ?1 large (21 kbp) deletion per 70 rounds of passage. Viruses produced using DNA reactivation appeared no different from recombinants produced using ordinary methods. An attractive feature of this approach is that when it is combined with selection for a particular phenotype, it provides a way of mapping and dissecting more complex virus traits. IMPORTANCE When two closely related viruses coinfect the same cell, they can swap genetic information through a process called recombination. Recombination produces new viruses bearing different combinations of genes, and it plays an important role in virus evolution. Poxviruses are a family of viruses that includes variola (or smallpox) virus, and although poxviruses are known to recombine, no one has previously mapped the patterns of DNAs exchanged between viruses. We coinfected cells with two different vaccinia poxviruses, isolated the progeny, and sequenced them. We show that poxvirus recombination is a very accurate process that assembles viruses containing DNA copied from both parents. In a single round of infection, DNA is swapped back and forth ?18 times per genome to make recombinant viruses that are a mosaic of the two parental DNAs. This mixes many different genes in complex combinations and illustrates how recombination can produce viruses with greatly altered disease potential. PMID:24574414

Qin, Li

2014-01-01

99

Attenuation and immunogenicity of host-range extended modified vaccinia virus Ankara recombinants  

PubMed Central

Modified vaccinia virus Ankara (MVA) is being widely investigated as a safe smallpox vaccine and as an expression vector to produce vaccines against other infectious diseases and cancer. MVA was isolated following more than 500 passages in chick embryo fibroblasts and suffered several major deletions and numerous small mutations resulting in replication defects in human and most other mammalian cells as well as severe attenuation of pathogenicity. Due to the host range restriction, primary chick embryo fibroblasts are routinely used for production of MVA-based vaccines. While a replication defect undoubtedly contributes to safety of MVA, it is worth considering whether host range and attenuation are partially separable properties. Marker rescue transfection experiments resulted in the creation of recombinant MVAs with extended mammalian cell host range. Here, we characterize two host-range extended rMVAs and show that they (i) have acquired the ability to stably replicate in Vero cells, which are frequently used as a cell substrate for vaccine manufacture (ii) are severely attenuated in immunocompetent and immunodeficient mouse strains following intranasal infection, (iii) are more pathogenic than MVA but less pathogenic than the ACAM2000 vaccine strain at high intracranial doses, (iv) do not form lesions upon tail scratch in mice in contrast to ACAM2000 and (v) induce protective humoral and cell-mediated immune responses similar to MVA. The extended host range of rMVAs may be useful for vaccine production. PMID:23928462

Melamed, Sharon; Wyatt, Linda S.; Kastenmayer, Robin J.; Moss, Bernard

2013-01-01

100

The development and use of a vaccinia-rabies recombinant oral vaccine for the control of wildlife rabies; a link between Jenner and Pasteur.  

PubMed Central

To improve both safety and stability of the oral vaccines used in the field to vaccinate foxes against rabies, a recombinant vaccinia virus, which expresses the immunizing G protein of rabies virus has been developed by inserting the cDNA which codes for the immunogenic glycoprotein of rabies virus into the thymidine kinase (TK) gene of the Copenhagen strain of vaccinia virus. The efficacy of this vaccine was tested by the oral route, primarily in foxes. The immunity conferred, a minimum of 12 months in cubs and 18 months in adult animals, corresponds to the duration of the protection required for vaccination of foxes in the field. Innocuity was tested in foxes, domestic animals, and in numerous European wild animal species that could compete with the red fox for the vaccine bait. No clinical signs or lesions were observed in any of the vaccinated animals during a minimum of 28 days post vaccination. Moreover, no transmission of immunizing doses of the recombinant occurred between foxes or other species tested. To study the stability of the vaccine strain, baits containing the vaccine were placed in the field. Despite considerable variations of environmental temperatures, the vaccine remained stable for at least one month. Because bait is taken within one month, it can be assumed that most animals taking the baits are effectively vaccinated. To test the field efficacy of the recombinant vaccine, large-scale campaigns of fox vaccination were set up in a 2200 km2 region of southern Belgium, were rabies was prevalent. A dramatic decrease in the incidence of rabies was noted after the campaigns. The recombinant is presently used to control wildlife rabies in the field both in several European countries and in the United States. PMID:8666066

Pastoret, P. P.; Brochier, B.

1996-01-01

101

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.  

Code of Federal Regulations, 2012 CFR

...Definition. PVEM is, for the purposes of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia...central nervous system impairments such as paralysis, seizure disorders, or developmental delays are known to occur as...

2012-10-01

102

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.  

Code of Federal Regulations, 2011 CFR

...Definition. PVEM is, for the purposes of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia...central nervous system impairments such as paralysis, seizure disorders, or developmental delays are known to occur as...

2011-10-01

103

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.  

Code of Federal Regulations, 2010 CFR

...Definition. PVEM is, for the purposes of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia...central nervous system impairments such as paralysis, seizure disorders, or developmental delays are known to occur as...

2010-10-01

104

42 CFR 102.21 - Smallpox (Vaccinia) Vaccine Injury Table.  

Code of Federal Regulations, 2013 CFR

...Definition. PVEM is, for the purposes of the Table, an autoimmune central nervous system injury. In rare cases, the vaccinia...central nervous system impairments such as paralysis, seizure disorders, or developmental delays are known to occur as...

2013-10-01

105

Recombinant Vaccinia Virus-Induced T-Cell Immunity: Quantitation of the Response to the Virus Vector and the Foreign Epitope  

Microsoft Academic Search

Recombinant vaccinia viruses (rVV) have been extensively used as vaccines, but there is little information about the total magnitude of the VV-specific T-cell response and how this compares to the immune response to the foreign gene(s) expressed by the rVV. To address this issue, we quantitated the T-cell responses to both the viral vector and the insert following the infection

Laurie E. Harrington; J. Lindsay Whitton; Rafi Ahmed

2002-01-01

106

Construction of Poxviruses as Cloning Vectors: Insertion of the Thymidine Kinase Gene from Herpes Simplex Virus into the DNA of Infectious Vaccinia Virus  

Microsoft Academic Search

We have constructed recombinant vaccinia viruses containing the thymidine kinase gene from herpes simplex virus. The gene was inserted into the genome of a variant of vaccinia virus that had undergone spontaneous deletion as well as into the 120-megadalton genome of the large prototypic vaccinia variant. This was accomplished via in vivo recombination by contransfection of eukaryotic tissue culture cells

Dennis Panicali; Enzo Paoletti

1982-01-01

107

Vaccinia virus strain differences in cell attachment and entry  

SciTech Connect

Vaccinia virus (VACV) strain WR can enter cells by a low pH endosomal pathway or direct fusion with the plasma membrane at neutral pH. Here, we compared attachment and entry of five VACV strains in six cell lines and discovered two major patterns. Only WR exhibited pH 5-enhanced rate of entry following neutral pH adsorption to cells, which correlated with sensitivity to bafilomycin A1, an inhibitor of endosomal acidification. Entry of IHD-J, Copenhagen and Elstree strains were neither accelerated by pH 5 treatment nor prevented by bafilomycin A1. Entry of the Wyeth strain, although not augmented by pH 5, was inhibited by bafilomycin A1. WR and Wyeth were both relatively resistant to the negative effects of heparin on entry, whereas the other strains were extremely sensitive due to inhibition of cell binding. The relative sensitivities of individual vaccinia virus strains to heparin correlated inversely with their abilities to bind to and enter glycosaminoglycan-deficient sog9 cells but not other cell lines tested. These results suggested that that IHD-J, Copenhagen and Elstree have a more limited ability than WR and Wyeth to use the low pH endosomal pathway and are more dependent on binding to glycosaminoglycans for cell attachment.

Bengali, Zain; Townsley, Alan C. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, Bethesda, MD 20892-3210 (United States); Moss, Bernard, E-mail: bmoss@nih.go [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 33 North Drive, Bethesda, MD 20892-3210 (United States)

2009-06-20

108

Molecular Chaperone Hsp90 Is Important for Vaccinia Virus Growth in Cells  

Microsoft Academic Search

Molecular chaperones assist protein folding, and some chaperones are induced by heat, nutrient depletion, or pathogen invasion. This study investigates the role played by Hsp90 in the life cycle of vaccinia virus. The titer of vaccinia intracellular mature virions (IMV) was reduced by 2 orders of magnitude in RK13 cells treated with geldanamycin (GA), which blocks the ATPase activity of

Jan-Jong Hung; Che-Sheng Chung; Wen Chang

2002-01-01

109

Spread of vaccinia virus through shaving during military training, Joint Base San Antonio-Lackland, TX, June 2014.  

PubMed

Although naturally occurring smallpox virus was officially declared eradicated in 1980, concern for biological warfare prompted the U.S. Government in 2002 to recommend smallpox vaccination for select individuals. Vaccinia, the smallpox vaccine virus, is administered into the skin, typically on the upper arm, where the virus remains viable and infectious until the scab falls off and the epidermis is fully intact - typically 2-4 weeks. Adverse events following smallpox vaccination may occur in the vaccinee, in individuals who have contact with the vaccinee (i.e., secondary transmission), or in individuals who have contact with the vaccinee's contact (i.e., tertiary transmission). In June 2014 at Joint Base San Antonio-Lackland, TX, two cases of inadvertent inoculation of vaccinia and one case of a non-viral reaction following vaccination occurred in the security forces training squadron. This includes the first reported case of shaving as the likely source of autoinoculation after contact transmission. This paper describes the diagnosis and treatment of these cases, the outbreak investigation, and steps taken to prevent future transmission. PMID:25162496

Webber, Bryant J; Montgomery, Jay R; Markelz, Ana E; Allen, Kahtonna C; Hunninghake, John C; Ritchie, Simon A; Pawlak, Mary T; Johnston, Lindsay A; Oliver, Tiffany A; Winterton, Brad S

2014-08-01

110

Immune Modulation in Primary Vaccinia virus Zoonotic Human Infections  

PubMed Central

In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+ cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans. PMID:22229039

Gomes, Juliana Assis Silva; de Araújo, Fernanda Fortes; Trindade, Giliane de Souza; Quinan, Bárbara Resende; Drumond, Betânia Paiva; Ferreira, Jaqueline Maria Siqueira; Mota, Bruno Eduardo Fernandes; Nogueira, Maurício Lacerda; Kroon, Erna Geessien; Abrahăo, Jônatas Santos; Côrrea-Oliveira, Rodrigo; da Fonseca, Flávio Guimarăes

2012-01-01

111

Expression of Herpes Simplex Virus 1 Glycoprotein B by a Recombinant Vaccinia Virus and Protection of Mice against Lethal Herpes Simplex Virus 1 Infection  

NASA Astrophysics Data System (ADS)

The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.

Cantin, Edouard M.; Eberle, Richard; Baldick, Joseph L.; Moss, Bernard; Willey, Dru E.; Notkins, Abner L.; Openshaw, Harry

1987-08-01

112

Profile of natural killer cells after a previous natural Vaccinia virus infection in an in vitro viral re-exposure.  

PubMed

The present study compares the profile of NK cells in an in vitro re-exposure by Vaccinia virus (VACV), in groups that have had a previous vaccination or natural infection. Our data suggests that stimulation with VACV triggers a cytotoxic response by NK cells marked by an increase of NCRs: NKp30, NKp44, and NKp46 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. However, the degranulation and secretion processes are inhibited in infected (vaccinated and unvaccinated) subjects and in the non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. We demonstrated that stimulation with VACV downregulates the percentage of expression of Perforin, Granzyme A, and CD107a, but upregulate CD94 in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals. Furthermore, the percentage of IFN-?(+) NK cells was significantly lower in non-infected unvaccinated subjects, when compared with infected (vaccinated and unvaccinated) and non-infected vaccinated individuals. Our results also show that the percentage of TNF-?(+) NK cells was significantly higher in infected (vaccinated and unvaccinated) subjects and in non-infected vaccinated patients, when compared with non-infected unvaccinated individuals, after in vitro stimulation with UV-inactivated VACV. Our data suggest that the expression of NCRs NKp30, NKp44, NKp46 and cytokines by NK cells are important in the innate response against VACV. PMID:24530576

Moreira-Silva, Eduardo Augusto dos Santos; Medeiros-Silva, Daniela Carla; Gomes, Juliana de Assis Silva; da Fonseca, Flávio Guimarăes; Correa-Oliveira, Rodrigo

2014-05-12

113

The Lipid Raft-Associated Protein CD98 Is Required for Vaccinia Virus Endocytosis  

PubMed Central

Mature vaccinia virus (vaccinia MV) infects a broad range of animals in vivo and cell cultures in vitro; however, the cellular receptors that determine vaccinia MV tropism and entry pathways are poorly characterized. Here, we performed quantitative proteomic analyses of lipid raft-associated proteins upon vaccinia MV entry into HeLa cells. We found that a type II membrane glycoprotein, CD98, is enriched in lipid rafts upon vaccinia MV infection compared to mock-infected HeLa cells. The knockdown of CD98 expression in HeLa cells significantly reduced vaccinia MV entry. Furthermore, CD98 knockout (KO) mouse embryonic fibroblasts (MEFs) also exhibited reduced vaccinia MV infectivity without affecting MV attachment to cells, suggesting a role for CD98 in the postbinding step of virus entry. Further characterization with inhibitors and dominant negative proteins that block different endocytic pathways revealed that vaccinia MV entry into MEFs occurs through a clathrin-independent, caveolin-independent, dynamin-dependent, fluid-phase endocytic pathway, implying that CD98 plays a specific role in the vaccinia MV endocytic pathway. Infections of wild-type and CD98 KO MEF cells with different strains of vaccinia MV provided further evidence that CD98 plays a specific role in MV endocytosis but not in plasma membrane fusion. Finally, different CD98-C69 chimeric proteins were expressed in CD98 KO MEFs, but none were able to reconstitute MV infectivity, suggesting that the overall structure of the CD98 protein is required for vaccinia MV endocytosis. PMID:22345471

Schroeder, Nina; Chung, Che-Sheng; Chen, Chein-Hung; Liao, Chung-Lin

2012-01-01

114

Construction of Poxviruses as Cloning Vectors: Insertion of the Thymidine Kinase Gene from Herpes Simplex Virus into the DNA of Infectious Vaccinia Virus  

NASA Astrophysics Data System (ADS)

We have constructed recombinant vaccinia viruses containing the thymidine kinase gene from herpes simplex virus. The gene was inserted into the genome of a variant of vaccinia virus that had undergone spontaneous deletion as well as into the 120-megadalton genome of the large prototypic vaccinia variant. This was accomplished via in vivo recombination by contransfection of eukaryotic tissue culture cells with cloned BamHI-digested thymidine kinase gene from herpes simplex virus containing flanking vaccinia virus DNA sequences and infectious rescuing vaccinia virus. Pure populations of the recombinant viruses were obtained by replica filter techniques or by growth of the recombinant virus in biochemically selective medium. The herpes simplex virus thymidine kinase gene, as an insert in vaccinia virus, is transcribed in vivo and in vitro, and the fidelity of in vivo transcription into a functional gene product was detected by the phosphorylation of 5-[125I]iodo-2'-deoxycytidine.

Panicali, Dennis; Paoletti, Enzo

1982-08-01

115

Identification of Novel Antipoxviral Agents: Mitoxantrone Inhibits Vaccinia Virus Replication by Blocking Virion Assembly?  

PubMed Central

The bioterror threat of a smallpox outbreak in an unvaccinated population has mobilized efforts to develop new antipoxviral agents. By screening a library of known drugs, we identified 13 compounds that inhibited vaccinia virus replication at noncytotoxic doses. The anticancer drug mitoxantrone is unique among the inhibitors identified in that it has no apparent impact on viral gene expression. Rather, it blocks processing of viral structural proteins and assembly of mature progeny virions. The isolation of mitoxantrone-resistant vaccinia strains underscores that a viral protein is the likely target of the drug. Whole-genome sequencing of mitoxantrone-resistant viruses pinpointed missense mutations in the N-terminal domain of vaccinia DNA ligase. Despite its favorable activity in cell culture, mitoxantrone administered intraperitoneally at the maximum tolerated dose failed to protect mice against a lethal intranasal infection with vaccinia virus. PMID:17928345

Deng, Liang; Dai, Peihong; Ciro, Anthony; Smee, Donald F.; Djaballah, Hakim; Shuman, Stewart

2007-01-01

116

Deletion of the vaccinia virus growth factor gene reduces virus virulence.  

PubMed Central

The vaccinia virus growth factor (VGF) gene encodes a polypeptide with amino acid sequence homology to epidermal growth factor (EGF) and transforming growth factor alpha and is present twice, once at each end of the virus genome within the inverted terminal repetition. Recombination procedures were used to replace more than half of both VGF genes with a beta-galactosidase cassette which served as a color indicator for isolating an unconditionally viable VGF- mutant. The VGF- mutant genotype and phenotype were confirmed by Southern blot analysis and assays for functional growth factor. The plaque-forming efficiencies of VGF- and wild-type (WT) viruses were similar in a variety of cell types containing low or high densities of EGF receptors, suggesting a lack of a specific requirement for either VGF or the EGF receptor in the initiation of virus infection. The yield of VGF- virus was similar to that of WT virus in growing BS-C-1 and Swiss 3T3 cells, but lower in resting Swiss 3T3 cells. The greatest differences between VGF- and WT virus occurred in vivo: higher doses of VGF- virus than WT virus were required for intracranial lethality in mice and for production of skin lesions in rabbits. Thus, expression of the VGF gene is important to the virulence of vaccinia virus. Images PMID:3339716

Buller, R M; Chakrabarti, S; Cooper, J A; Twardzik, D R; Moss, B

1988-01-01

117

Multiple Viral Ligands Naturally Presented by Different Class I Molecules in Transporter Antigen Processing-Deficient Vaccinia Virus-Infected Cells  

PubMed Central

The transporter associated with antigen processing (TAP) delivers the viral proteolytic products generated by the proteasome in the cytosol to the endoplasmic reticulum lumen that are subsequently recognized by cytotoxic T lymphocytes (CTLs). However, several viral epitopes have been identified in TAP-deficient models. Using mass spectrometry to analyze complex human leukocyte antigen (HLA)-bound peptide pools isolated from large numbers of TAP-deficient vaccinia virus-infected cells, we identified 11 ligands naturally presented by four different HLA-A, HLA-B, and HLA-C class I molecules. Two of these ligands were presented by two different HLA class I alleles, and, as a result, 13 different HLA-peptide complexes were formed simultaneously in the same vaccinia virus-infected cells. In addition to the high-affinity ligands, one low-affinity peptide restricted by each of the HLA-A, HLA-B, and HLA-C class I molecules was identified. Both high- and low-affinity ligands generated long-term memory CTL responses to vaccinia virus in an HLA-A2-transgenic mouse model. The processing and presentation of two vaccinia virus-encoded HLA-A2-restricted antigens took place via proteasomal and nonproteasomal pathways, which were blocked in infected cells with chemical inhibitors specific for different subsets of metalloproteinases. These data have implications for the study of the effectiveness of early empirical vaccination with cowpox virus against smallpox disease. PMID:22031944

Lorente, Elena; Infantes, Susana; Barnea, Eilon; Beer, Ilan; Garcia, Ruth; Lasala, Fatima; Jimenez, Mercedes; Vilches, Carlos; Lemonnier, Francois A.; Admon, Arie

2012-01-01

118

Characterization of Chimpanzee\\/Human Monoclonal Antibodies to Vaccinia Virus A33 Glycoprotein and Its Variola Virus Homolog In Vitro and in a Vaccinia Virus Mouse Protection Model  

Microsoft Academic Search

Three distinct chimpanzee Fabs against the A33 envelope glycoprotein of vaccinia virus were isolated and converted into complete monoclonal antibodies (MAbs) with human 1 heavy-chain constant regions. The three MAbs (6C, 12C, and 12F) displayed high binding affinities to A33 (Kd of 0.14 nM to 20 nM) and may recognize the same epitope, which was determined to be conformational and

Zhaochun Chen; Patricia Earl; Jeffrey Americo; Inger Damon; Scott K. Smith; Fujuan Yu; Andrew Sebrell; Suzanne Emerson; Gary Cohen; Roselyn J. Eisenberg; Inna Gorshkova; Peter Schuck; William Satterfield; Bernard Moss; Robert Purcell

2007-01-01

119

A comparison of the antigens present on the surface of virus released artificially from chick cells infected with vaccinia virus, and cowpox virus and its white pock mutant  

PubMed Central

Antisera prepared against vaccinia and cowpox viruses were absorbed with purified suspensions of vaccinia virus, red cowpox and white cowpox viruses. They were then tested for their ability to neutralize the viruses, and to precipitate the virus soluble antigens. The results showed that some virus specific antigens were not virus surface components and that some components were present on the surface of all three viruses. However, certain components were detected on the surface of vaccinia virus but not on the surface of cowpox virus, and vice versa. Some evidence for the existence of a vaccinia-specific surface component was also obtained. Comparisons between results of cross-neutralization tests and immunodiffusion tests on the absorbed sera indicated that antibody to a number of antigens, including the classical LS, and the cowpox-specific d antigen play no part in the process of poxvirus neutralization. ImagesFig. AFig. BFig. CFig. DFig. EFig. FFig. G PMID:4624399

Baxby, Derrick

1972-01-01

120

Vaccinia Virus 4c (A26L) Protein on Intracellular Mature Virus Binds to the Extracellular Cellular Matrix Laminin  

Microsoft Academic Search

Vaccinia virus intracellular mature virus (IMV) binds to glycosaminoglycans (GAGs) on cells via three virion proteins, H3L, A27L, and D8L. In this study, we demonstrated that binding of IMV to BSC40 cells was competitively inhibited by soluble laminin but not by fibronectin or collagen V, suggesting that this cell surface extracellular matrix (ECM) protein may play a role in vaccinia

Wen-Ling Chiu; Chi-Long Lin; Min-Hsiang Yang; Der-Lii M. Tzou; Wen Chang

2007-01-01

121

Atomic Force Microscopy Investigation of Vaccinia Virus Structure?  

PubMed Central

Vaccinia virus was treated in a controlled manner with various combinations of nonionic detergents, reducing agents, and proteolytic enzymes, and successive products of the reactions were visualized using atomic force microscopy (AFM). Following removal of the outer lipid/protein membrane, a layer 20 to 40 nm in thickness was encountered that was composed of fibrous elements which, under reducing conditions, rapidly decomposed into individual monomers on the substrate. Beneath this layer was the virus core and its prominent lateral bodies, which could be dissociated or degraded with proteases. The core, in addition to the lateral bodies, was composed of a thick, multilayered shell of proteins of diverse sizes and shapes. The shell, which was readily etched with proteases, was thoroughly permeated with pores, or channels. Prolonged exposure to proteases and reductants produced disgorgement of the viral DNA from the remainders of the cores and also left residual, flattened, protease-resistant sacs on the imaging substrate. The DNA was readily visualized by AFM, which revealed some regions to be “soldered” by proteins, others to be heavily complexed with protein, and yet other parts to apparently exist as bundled, naked DNA. Prolonged exposure to proteases deproteinized the DNA, leaving masses of extended, free DNA. Estimates of the interior core volume suggest moderate but not extreme compaction of the genome. PMID:18508898

Kuznetsov, Y.; Gershon, P. D.; McPherson, A.

2008-01-01

122

Virus-vectored influenza virus vaccines.  

PubMed

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines. PMID:25105278

Tripp, Ralph A; Tompkins, S Mark

2014-08-01

123

Sensors and Actuators B xxx (2005) xxxxxx Characterization of vaccinia virus particles using microscale silicon  

E-print Network

microscopy and micron-scale cantilever beams, with the long-term goal of developing devices for the direct microscale silicon cantilever resonators and atomic force microscopy Luke Johnson1, Amit K. Gupta, Azam variety of applications. We have used vaccinia virus, a member of the Poxviridae virus family

Bashir, Rashid

124

Systemically administered DNA and fowlpox recombinants expressing four vaccinia virus genes although immunogenic do not protect mice against the highly pathogenic IHD-J vaccinia strain.  

PubMed

The first-generation smallpox vaccine was based on live vaccinia virus (VV) and it successfully eradicated the disease worldwide. Therefore, it was not administered any more after 1980, as smallpox no longer existed as a natural infection. However, emerging threats by terrorist organisations has prompted new programmes for second-generation vaccine development based on attenuated VV strains, which have been shown to cause rare but serious adverse events in immunocompromised patients. Considering the closely related animal poxviruses that might also be used as bioweapons, and the increasing number of unvaccinated young people and AIDS-affected immunocompromised subjects, a safer and more effective smallpox vaccine is still required. New avipoxvirus-based vectors should improve the safety of conventional vaccines, and protect from newly emerging zoonotic orthopoxvirus diseases and from the threat of deliberate release of variola or monkeypox virus in a bioterrorist attack. In this study, DNA and fowlpox recombinants expressing the L1R, A27L, A33R and B5R genes were constructed and evaluated in a pre-clinical trial in mouse, following six prime/boost immunisation regimens, to compare their immunogenicity and protective efficacy against a challenge with the lethal VV IHD-J strain. Although higher numbers of VV-specific IFN?-producing T lymphocytes were observed in the protected mice, the cytotoxic T-lymphocyte response and the presence of neutralising antibodies did not always correlate with protection. In spite of previous successful results in mice, rabbits and monkeys, where SIV/HIV transgenes were expressed by the fowlpox vector, the immune response elicited by these recombinants was low, and most of the mice were not protected. PMID:24050999

Bissa, Massimiliano; Pacchioni, Sole Maria; Zanotto, Carlo; De Giuli Morghen, Carlo; Illiano, Elena; Granucci, Francesca; Zanoni, Ivan; Broggi, Achille; Radaelli, Antonia

2013-12-26

125

killed-virus influenza vaccine Polio vaccine  

E-print Network

killed-virus influenza vaccine Polio vaccine FluMist Thomas Francis, Jr. National Institutes of Michigan's Rackham Auditorium and watched Thomas Francis Jr. announce to the world that the polio vaccine petitioned to spend a year or two in Francis's lab. Indeed, Jonas Salk, developer of the Salk polio vac- cine

Shyy, Wei

126

Antibodies, viruses and vaccines  

Microsoft Academic Search

Neutralizing antibodies are crucial for vaccine-mediated protection against viral diseases. They probably act, in most cases, by blunting the infection, which is then resolved by cellular immunity. The protective effects of neutralizing antibodies can be achieved not only by neutralization of free virus particles, but also by several activities directed against infected cells. In certain instances, non-neutralizing antibodies contribute to

Dennis R. Burton

2002-01-01

127

Synthetic oligonucleotide expressed by a recombinant vaccinia virus elicits therapeutic CTL.  

PubMed

P815A is a naturally occurring tumor rejection Ag of the methylcholanthrene-induced murine mastocytoma P815. The gene encoding the Ag P815A, designated P1A, is identical to that encoded in the normal genome of the DBA/2 mouse. A recombinant vaccinia virus (rVV) was constructed that expressed a synthetic oligonucleotide encoding the minimal determinant peptide of the tumor-associated Ag. Although the rVV recombinant expressing this mini-gene was recognized efficiently in vitro, it was an ineffective immunogen in vivo. The addition of an endoplasmic reticulum insertion signal sequence to the NH2 terminus of the minimal determinant resulted in a rVV that elicited CD8+ T cells that could lyse P815 mastocytoma cells in vitro and that were therapeutic in vivo. Recombinant viruses expressing synthetic oligonucleotide sequences preceded by the insertion signal sequences allow the expression of Ag directly into the endoplasmic reticulum, where binding to MHC class I molecules is most efficient. Vaccines based on synthetic oligonucleotides could be constructed with ease and rapidity but, most importantly, such constructs avoid the dangers associated with the expression of full length genes encoding TAA that are potentially oncogenic. PMID:7722317

Irvine, K R; McCabe, B J; Rosenberg, S A; Restifo, N P

1995-05-01

128

Stunned Silence: Gene Expression Programs in Human Cells Infected with Monkeypox or Vaccinia Virus  

PubMed Central

Poxviruses use an arsenal of molecular weapons to evade detection and disarm host immune responses. We used DNA microarrays to investigate the gene expression responses to infection by monkeypox virus (MPV), an emerging human pathogen, and Vaccinia virus (VAC), a widely used model and vaccine organism, in primary human macrophages, primary human fibroblasts and HeLa cells. Even as the overwhelmingly infected cells approached their demise, with extensive cytopathic changes, their gene expression programs appeared almost oblivious to poxvirus infection. Although killed (gamma-irradiated) MPV potently induced a transcriptional program characteristic of the interferon response, no such response was observed during infection with either live MPV or VAC. Moreover, while the gene expression response of infected cells to stimulation with ionomycin plus phorbol 12-myristate 13-acetate (PMA), or poly (I-C) was largely unimpaired by infection with MPV, a cluster of pro-inflammatory genes were a notable exception. Poly(I-C) induction of genes involved in alerting the innate immune system to the infectious threat, including TNF-alpha, IL-1 alpha and beta, CCL5 and IL-6, were suppressed by infection with live MPV. Thus, MPV selectively inhibits expression of genes with critical roles in cell-signaling pathways that activate innate immune responses, as part of its strategy for stealthy infection. PMID:21267444

Rubins, Kathleen H.; Hensley, Lisa E.; Relman, David A.; Brown, Patrick O.

2011-01-01

129

Unpolarized Release of Vaccinia Virus and HIV Antigen by Colchicine Treatment Enhances Intranasal HIV Antigen Expression and Mucosal Humoral Responses  

PubMed Central

The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies. PMID:21935396

Zhang, Yan; Yang, Jingyi; Bao, Rong; Chen, Yaoqing; Zhou, Dihan; He, Benxia; Zhong, Maohua; Li, Yaoming; Liu, Fang; Li, Qiaoli; Yang, Yi; Han, Chen; Sun, Ying; Cao, Yuan; Yan, Huimin

2011-01-01

130

TRAF2 Facilitates Vaccinia Virus Replication by Promoting Rapid Virus Entry  

PubMed Central

ABSTRACT Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) is a pivotal intracellular mediator of signaling pathways downstream of TNFR1 and -2 with known pro- and antiviral effects. We investigated its role in the replication of the prototype poxvirus vaccinia virus (VACV). Loss of TRAF2 expression, either through small interfering RNA treatment of HeLa cells or through genetic knockout in murine embryonic fibroblasts (MEFs), led to significant reductions in VACV growth following low-multiplicity infection. In single-cycle infections, there was delayed production of both early and late VACV proteins as well as accelerated virus-induced alterations to cell morphology, indicating that TRAF2 influences early stages of virus replication. Consistent with an early role, uncoating assays showed normal virus attachment but delayed virus entry in the absence of TRAF2. Although alterations to c-Jun N-terminal kinase (JNK) signaling were apparent in VACV-infected TRAF2?/? MEFs, treatment of wild-type cells with a JNK inhibitor did not affect virus entry. Instead, treatment with an inhibitor of endosomal acidification greatly reduced virus entry into TRAF2?/? MEFs, suggesting that VACV is reliant on the endosomal route of entry in the absence of TRAF2. Thus, TRAF2 is a proviral factor for VACV that plays a role in promoting efficient viral entry, most likely via the plasma membrane. IMPORTANCE Tumor necrosis factor receptor-associated factors (TRAFs) are key facilitators of intracellular signaling with roles in innate and adaptive immunity and stress responses. We have discovered that TRAF2 is a proviral factor in vaccinia virus replication in both HeLa cells and mouse embryonic fibroblasts and that its influence is exercised through promotion of efficient virus entry. PMID:24429366

Haga, Ismar R.; Pechenick Jowers, Tali; Griffiths, Samantha J.; Haas, Juergen

2014-01-01

131

High, Broad, Polyfunctional, and Durable T Cell Immune Responses Induced in Mice by a Novel Hepatitis C Virus (HCV) Vaccine Candidate (MVA-HCV) Based on Modified Vaccinia Virus Ankara Expressing the Nearly Full-Length HCV Genome  

PubMed Central

A major goal in the control of hepatitis C infection is the development of a vaccine. Here, we have developed a novel HCV vaccine candidate based on the highly attenuated poxvirus vector MVA (referred to as MVA-HCV) expressing the nearly full-length (7.9-kbp) HCV sequence, with the aim to target almost all of the T and B cell determinants described for HCV. In infected cells, MVA-HCV produces a polyprotein that is subsequently processed into the structural and nonstructural HCV proteins, triggering the cytoplasmic accumulation of dense membrane aggregates. In both C57BL/6 and transgenic HLA-A2-vaccinated mice, MVA-HCV induced high, broad, polyfunctional, and long-lasting HCV-specific T cell immune responses. The vaccine-induced T cell response was mainly mediated by CD8 T cells; however, although lower in magnitude, the CD4+ T cells were highly polyfunctional. In homologous protocol (MVA-HCV/MVA-HCV) the main CD8+ T cell target was p7+NS2, whereas in heterologous combination (DNA-HCV/MVA-HCV) the main target was NS3. Antigenic responses were also detected against other HCV proteins (Core, E1-E2, and NS4), but the magnitude of the responses was dependent on the protocol used. The majority of the HCV-induced CD8+ T cells were triple or quadruple cytokine producers. The MVA-HCV vaccine induced memory CD8+ T cell responses with an effector memory phenotype. Overall, our data showed that MVA-HCV induced broad, highly polyfunctional, and durable T cell responses of a magnitude and quality that might be associated with protective immunity and open the path for future considerations of MVA-HCV as a prophylactic and/or therapeutic vaccine candidate against HCV. PMID:23596307

Gomez, Carmen E.; Perdiguero, Beatriz; Cepeda, Maria Victoria; Mingorance, Lidia; Garcia-Arriaza, Juan; Vandermeeren, Andrea; Sorzano, Carlos Oscar S.

2013-01-01

132

Enhanced T cell-mediated protection against malaria in human challenges by using the recombinant poxviruses FP9 and modified vaccinia virus Ankara  

PubMed Central

Malaria is a major global health problem for which an effective vaccine is required urgently. Prime-boost vaccination regimes involving plasmid DNA and recombinant modified vaccinia virus Ankara-encoding liver-stage malaria antigens have been shown to be powerfully immunogenic for T cells and capable of inducing partial protection against experimental malaria challenge in humans, manifested as a delay in time to patent parasitemia. Here, we report that substitution of plasmid DNA as the priming vector with a specific attenuated recombinant fowlpox virus, FP9, vaccine in such prime-boost regimes can elicit complete sterile protection that can last for 20 months. Protection at 20 months was associated with persisting memory but not effector T cell responses. The protective efficacy of various immunization regimes correlated with the magnitude of induced immune responses, supporting the strategy of maximizing durable T cell immunogenicity to develop more effective liver-stage vaccines against Plasmodium falciparum malaria. PMID:15781866

Webster, Daniel P.; Dunachie, Susanna; Vuola, Jenni M.; Berthoud, Tamara; Keating, Sheila; Laidlaw, Stephen M.; McConkey, Samuel J.; Poulton, Ian; Andrews, Laura; Andersen, Rikke F.; Bejon, Philip; Butcher, Geoff; Sinden, Robert; Skinner, Michael A.; Gilbert, Sarah C.; Hill, Adrian V. S.

2005-01-01

133

Rapid inactivation of vaccinia virus in suspension and dried on surfaces.  

PubMed

A bioterrorist attack with smallpox virus would be disastrous with a 30% disease fatality rate. Such an outbreak would require biomedical laboratories for diagnosis and analyses and extensive use of clinical care facilities for patient quarantine. Safe decontamination procedures will have to be in place in order to limit the spread of the disease. In order to fulfil this need, Sanytex, a new non-corrosive commercial solution containing quaternary ammonium, aldehydes, alcohol and detergent, was tested with a view to using it in decontamination procedures. Vaccinia virus was used in this investigation as a model for smallpox virus. We determined exposure time and the concentration of Sanytex required to inactivate the virus in suspension and dried on surfaces in the presence of protein (up to 70 mg/mL). After 3 min incubation, Sanytex at a concentration of 3% led to a complete inactivation (virus titre reduction >10(4)-fold of vaccinia virus in suspension containing protein up to 30 mg/mL. A virus suspension containing 70 mg protein/mL, simulating biological fluids, was decontaminated with 10% Sanytex after 3 min. After 10 min, Sanytex at a concentration of 30%, applied on to a dried vaccinia virus contaminated surface in the presence of protein (10 mg/mL before desiccation), led to complete decontamination of the surface. Thirty minutes exposure with 30% Sanytex was necessary for a virus titre reduction of >10(4)-fold on a surface contaminated with a dried suspension of vaccinia virus in the presence of protein at 70 mg/mL. Sanytex is not corrosive, not toxic to environment and stable for up to three months even diluted. Its virucidal effect was preserved when used under pressure in a fire-hose nozzle. These results support the use of Sanytex for decontamination of biological fluids and surfaces contaminated by the smallpox virus. PMID:15142719

Ferrier, A; Garin, D; Crance, J M

2004-05-01

134

Capturing of cell culture-derived modified Vaccinia Ankara virus by ion exchange and pseudo-affinity membrane adsorbers.  

PubMed

Smallpox is an acute, highly infectious viral disease unique to humans, and responsible for an estimated 300-500 million deaths in the 20th century. Following successful vaccination campaigns through the 19th and 20th centuries, smallpox was declared eradicated by the World Health Organization in 1980. However, the threat of using smallpox as a biological weapon prompted efforts of some governments to produce smallpox vaccines for emergency preparedness. An additional aspect for the interest in smallpox virus is its potential use as a platform technology for vector vaccines. In particular, the latter requires a high safety level for routine applications. IMVAMUNE, a third generation smallpox vaccine based on the attenuated Modified Vaccinia Ankara (MVA) virus, demonstrates superior safety compared to earlier generations and represents therefore an interesting choice as viral vector. Current downstream production processes of Vaccinia virus and MVA are mainly based on labor-intensive centrifugation and filtration methods, requiring expensive nuclease treatment in order to achieve sufficient low host-cell DNA levels for human vaccines. This study compares different ion exchange and pseudo-affinity membrane adsorbers (MA) to capture chicken embryo fibroblast cell-derived MVA-BN after cell homogenization and clarification. In parallel, the overall performance of classical bead-based resin chromatography (Cellufine sulfate and Toyopearl AF-Heparin) was investigated. The two tested pseudo-affinity MA (i.e., sulfated cellulose and heparin) were superior over the applied ion exchange MA in terms of virus yield and contaminant depletion. Furthermore, studies confirmed an expected increase in productivity resulting from the increased volume throughput of MA compared to classical bead-based column chromatography methods. Overall virus recovery was approximately 60% for both pseudo-affinity MA and the Cellufine sulfate resin. Depletion of total protein ranged between 86% and 102% for all tested matrices. Remaining dsDNA in the product fraction varied between 24% and 7% for the pseudo-affinity chromatography materials. Cellufine sulfate and the reinforced sulfated cellulose MA achieved the lowest dsDNA product contamination. Finally, by a combination of pseudo-affinity with anion exchange MA a further reduction of host-cell DNA was achieved. PMID:19891005

Wolff, Michael W; Siewert, Corina; Lehmann, Sylvia; Hansen, Sara Post; Djurup, Rene; Faber, Rene; Reichl, Udo

2010-03-01

135

THE HUMAN SPLEEN IS A MAJOR RESERVOIR FOR LONG-LIVED VACCINIA VIRUS-SPECIFIC MEMORY B CELLS.  

E-print Network

- 1 - THE HUMAN SPLEEN IS A MAJOR RESERVOIR FOR LONG-LIVED VACCINIA VIRUS-SPECIFIC MEMORY B CELLS@necker.fr Running Title: Long-lived B cell memory in the spleen. Abbreviations: ITP, idiopathic thrombocytopenic published in Blood. Mamani-Matsuda et al. The human spleen is a major reservoir for long-lived vaccinia

Paris-Sud XI, Université de

136

Emergency medicine tools to manage smallpox (vaccinia) vaccination complications: clinical practice guideline and policies and procedures.  

PubMed

In December 2002, the federal government began a program to immunize approximately 500000 civilian public health and health care workers with smallpox (vaccinia) vaccine as a part of our pre-event defense against bioterrorism. First responders will likely follow, and the general US population might be offered vaccination in the next 1 to 2 years. Recent reports that suggest the possible association of the vaccine to adverse cardiac events (including deaths), liability concerns for hospitals, and the availability of compensation for workers with vaccine complications have significantly reduced voluntary participation. Vaccinees might experience robust primary takes or serious adverse events, including viral or even bacterial cellulitides, encephalitis, progressive skin destruction, and other life-threatening complications. With the increasing prevalence of immune suppression from both diseases and immunosuppressive medications, complications might be seen in higher frequency than previously reported. Emergency medicine providers and staff must become familiar with clinical presentations and management of vaccine complications. In addition, policies and procedures must be developed to prevent unimmunized providers from inadvertently contacting the active vaccination sites of their patients and, if the providers themselves have active vaccination sites, to protect their patients and their own families. PMID:14581920

Thorne, Craig D; Hirshon, Jon Mark; Himes, Carrie D; McDiarmid, Melissa A

2003-11-01

137

The Effect of X-Rays on Multiplication of the Vaccinia Virus in Tissue Culture.  

National Technical Information Service (NTIS)

X-ray irradiation of a 48-hour skin-muscle tissue culture of a chick embryo with a dose of 20 kr causes an increase in the infectivity titer of the vaccinia virus in the liquid fraction of the tissue culture 72 hours after infection. No difference is note...

L. A. Kamalyan, R. A. Ter-Pogosyan

1968-01-01

138

Identification of Novel Antipoxviral Agents: Mitoxantrone Inhibits Vaccinia Virus Replication by Blocking Virion Assembly  

Microsoft Academic Search

The bioterror threat of a smallpox outbreak in an unvaccinated population has mobilized efforts to develop new antipoxviral agents. By screening a library of known drugs, we identified 13 compounds that inhibited vaccinia virus replication at noncytotoxic doses. The anticancer drug mitoxantrone is unique among the inhibitors identified in that it has no apparent impact on viral gene expression. Rather,

Liang Deng; Peihong Dai; Anthony Ciro; Donald F. Smee; Hakim Djaballah; Stewart Shuman

2007-01-01

139

Human immunodeficiency virus-like, nonreplicating, gag-env particles assemble in a recombinant vaccinia virus expression system.  

PubMed Central

We report the assembly of human immunodeficiency virus (HIV)-like particles in African green monkey kidney cells coinfected with two recombinant vaccinia viruses, one carrying the HIV-1 gag and protease genes and the other the env gene. Biochemical analysis of particles sedimented from culture supernatants of doubly infected cells revealed that they were composed of gag proteins, primarily p24, as well as the env proteins gp120 and gp41. Thin-section immunoelectron microscopy showed that these particles were 100 to 120 nm in diameter, were characterized by the presence of cylindrical core structures, and displayed the mature gp120-gp41 complexes on their surfaces. Furthermore, thin-section immunoelectron microscopy analysis of infected cells showed that particle assembly and budding occurred at the plasma membrane. Nucleic acid hybridization suggested that the particles packaged only the gag mRNA but not the env mRNA. Therefore, the system we present is well suited for studies of HIV virion maturation. In addition, the HIV-like particles provide a novel and attractive approach for vaccine development. Images PMID:2186175

Haffar, O; Garrigues, J; Travis, B; Moran, P; Zarling, J; Hu, S L

1990-01-01

140

Immunization with recombinant vaccinia viruses expressing structural and part of the nonstructural region of tick-borne encephalitis virus cDNA protect mice against lethal encephalitis.  

PubMed

Three recombinant vaccinia viruses containing different fragments of tick-borne encephalitis virus (TBEV) cDNA representing the 5'-noncoding region (5'NCR), all structural and part of the nonstructural regions were constructed. Western blot analysis showed that E and NS1 proteins were expressed and processed correctly in cells infected with recombinant viruses vC-NS1 (coding for C-prM-E-NS1 region) and vC-NS3 (coding for C-prM-E-NS1-NS2A-NS2B-NS3 region). In contrast, in cells infected with recombinant virus v5'C-NS2A (coding for 5'NCR and C-prM-E-NS1-NS2A regions) expression of NS1 protein was greatly reduced and no E protein was detected. Immunization of mice with vC-NS3 induced high levels of TBEV-specific antibodies and protected them against intraperitoneal challenge with 10(7) LD50 of TBEV. The level of protection was very similar to the level of protection achieved by immunization with commercially available inactivated TBEV vaccine. Although the immunization of mice with recombinants vC-NS1 and v5'C-NS2A induced much lower levels of TBEV-specific antibodies, they were still protected against intraperitoneal challenge with 10(4) and 10(3.6) LD50 of TBEV, respectively. The high level of protection against TBEV infection achieved by the immunization of mice with the recombinant vaccinia virus vC-NS3 makes this virus a very attractive candidate for development of a live recombinant vaccine against TBEV. PMID:8717392

Dmitriev, I P; Khromykh, A A; Ignatyev, G M; Gainullina, M N; Ageenko, V A; Dryga, S A; Vorobyeva, M S; Sandakhchiev, L S

1996-01-26

141

Novel avian influenza virus vaccines.  

PubMed

Current vaccines against avian influenza (AI) virus infections are primarily based on classical inactivated whole-virus preparations. Although administration of these vaccines can protect poultry from clinical disease, sterile immunity is not achieved under field conditions, allowing for undetected virus spread and evolution under immune cover. Therefore, there is an urgent need for a robust and reliable system of differentiation between infected and vaccinated animals. Moreover, current AI vaccines must be administered individually, requiring the handling of excessively large numbers of animals, which makes it difficult to obtain high vaccine coverage. Consequently, AI vaccines conferring solid immunity that could be used for mass application would be advantageous. Several approaches are being pursued to improve existing vaccines and develop novel vaccines, all of which will be covered in this overview. PMID:19618635

Fuchs, W; Römer-Oberdörfer, A; Veits, J; Mettenleiter, T C

2009-04-01

142

Mapping of the vaccinia virus DNA polymerase gene by marker rescue and cell-free translation of selected RNA  

Microsoft Academic Search

The previous demonstration that a phosphonoacetate (PAA)-resistant (PAA\\/sup r\\/) vaccinia virus mutant synthesized an altered DNA polymerase provided the key to mapping this gene. Marker rescue was performed in cells infected with wild-type PAA-sensitive (PAA\\/sup s\\/) vaccinia by transfecting with calcium phosphate-precipitated DNA from a PAA\\/sup r\\/ mutant virus. Formation of PAA\\/sup r\\/ recombinants was measured by plaque assay in

E. V. Jones; B. Moss

1984-01-01

143

Recombinant Modified Vaccinia Virus Ankara Expressing Glycoprotein E2 of Chikungunya Virus Protects AG129 Mice against Lethal Challenge  

PubMed Central

Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections. PMID:25188230

van den Doel, Petra; Volz, Asisa; Roose, Jouke M.; Sewbalaksing, Varsha D.; Pijlman, Gorben P.; van Middelkoop, Ingeborg; Duiverman, Vincent; van de Wetering, Eva; Sutter, Gerd; Osterhaus, Albert D. M. E.; Martina, Byron E. E.

2014-01-01

144

Recombinant modified vaccinia virus Ankara expressing glycoprotein E2 of Chikungunya virus protects AG129 mice against lethal challenge.  

PubMed

Chikungunya virus (CHIKV) infection is characterized by rash, acute high fever, chills, headache, nausea, photophobia, vomiting, and severe polyarthralgia. There is evidence that arthralgia can persist for years and result in long-term discomfort. Neurologic disease with fatal outcome has been documented, although at low incidences. The CHIKV RNA genome encodes five structural proteins (C, E1, E2, E3 and 6K). The E1 spike protein drives the fusion process within the cytoplasm, while the E2 protein is believed to interact with cellular receptors and therefore most probably constitutes the target of neutralizing antibodies. We have constructed recombinant Modified Vaccinia Ankara (MVA) expressing E3E2, 6KE1, or the entire CHIKV envelope polyprotein cassette E3E26KE1. MVA is an appropriate platform because of its demonstrated clinical safety and its suitability for expression of various heterologous proteins. After completing the immunization scheme, animals were challenged with CHIV-S27. Immunization of AG129 mice with MVAs expressing E2 or E3E26KE1 elicited neutralizing antibodies in all animals and provided 100% protection against lethal disease. In contrast, 75% of the animals immunized with 6KE1 were protected against lethal infection. In conclusion, MVA expressing the glycoprotein E2 of CHIKV represents as an immunogenic and effective candidate vaccine against CHIKV infections. PMID:25188230

van den Doel, Petra; Volz, Asisa; Roose, Jouke M; Sewbalaksing, Varsha D; Pijlman, Gorben P; van Middelkoop, Ingeborg; Duiverman, Vincent; van de Wetering, Eva; Sutter, Gerd; Osterhaus, Albert D M E; Martina, Byron E E

2014-09-01

145

Oncolytic vaccinia virus demonstrates antiangiogenic effects mediated by targeting of VEGF.  

PubMed

Oncolytic vaccinia virus has been shown to induce a profound, rapid and tumor-specific vascular collapse in both preclinical models and clinical studies; however, a complete examination of the kinetics and levels of collapse and revascularization has not been described previously. Contrast-enhanced ultrasound was used to follow tumor perfusion levels in mouse tumor models at times after vaccinia therapy. It was observed that revascularization after viral therapy was dramatically delayed and did not occur until after viral clearance. This indicated that oncolytic vaccinia may possess a previously undescribed antiangiogenic potential that might synergize with the reported anti-vascular effects. Despite a rapid loss of perfusion and widespread hypoxia within the tumor, it was observed that VEGF levels in the tumor were suppressed throughout the period of active viral infection. Although tumor vasculature could eventually reform after the viral therapy was cleared in mouse models, anti-tumor effects could be significantly enhanced through additional combination with anti-VEGF therapies. This was initially examined using a gene therapy approach (Ad-Flk1-Fc) to target VEGF directly, demonstrating that the timing of application of the antiangiogenic therapy was critical. However, it is also known that oncolytic vaccinia sensitizes tumors to tyrosine kinase inhibitors (TKI) in the clinic through an unknown mechanism. It is possible this phenomenon may be mediated through the antiangiogenic effects of the TKIs. This was modeled in mouse tumors using sunitinib in combination with oncolytic vaccinia. It was observed that prevention of angiogenesis mediated by oncolytic vaccinia can be utilized to enhance the TKI therapy. PMID:24474587

Hou, Weizhou; Chen, Hannah; Rojas, Juan; Sampath, Padma; Thorne, Stephen H

2014-09-01

146

Heterologous Prime-Boost Vaccination with the LACK Antigen Protects against Murine Visceral Leishmaniasis  

Microsoft Academic Search

This study reports the efficacy of a heterologous prime-boost vaccination using DNA and vaccinia viruses (Western Reserve (WR) virus and modified (attenuated) vaccinia virus Ankara (MVA)) expressing the LACK antigen (Leishmania homologue of receptors for activated C kinase) and an intradermal murine infection model employing Leishmania infantum. At 1 month postinfection, vaccinated mice showed high levels of protection in the

Blaise Dondji; Eva Perez-Jimenez; Karen Goldsmith-Pestana; Mariano Esteban; D. McMahon-Pratt

2005-01-01

147

Dominant negative selection of vaccinia virus using a thymidine kinase/thymidylate kinase fusion gene and the prodrug azidothymidine  

SciTech Connect

The Escherichia coli thymidine kinase/thymidylate kinase (tk/tmk) fusion gene encodes an enzyme that efficiently converts the prodrug 3'-azido-2',3'-dideoxythymidine (AZT) into its toxic triphosphate derivative, a substance which stops DNA chain elongation. Integration of this marker gene into vaccinia virus that normally is not inhibited by AZT allowed the establishment of a powerful selection procedure for recombinant viruses. In contrast to the conventional vaccinia thymidine kinase (tk) selection that is performed in tk-negative cell lines, AZT selection can be performed in normal (tk-positive) cell lines. The technique is especially useful for the generation of replication-deficient vaccinia viruses and may also be used for gene knock-out studies of essential vaccinia genes.

Holzer, Georg W. [Baxter BioScience/Vaccines, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau (Austria); Mayrhofer, Josef [Baxter BioScience/Vaccines, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau (Austria); Gritschenberger, Werner [Baxter BioScience/Vaccines, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau (Austria); Falkner, Falko G. [Baxter BioScience/Vaccines, Biomedical Research Center, Uferstrasse 15, A-2304 Orth/Donau (Austria)]. E-mail: falknef@baxter.com

2005-07-05

148

New vaccines against influenza virus  

PubMed Central

Vaccination is one of the most effective and cost-benefit interventions that prevent the mortality and reduce morbidity from infectious pathogens. However, the licensed influenza vaccine induces strain-specific immunity and must be updated annually based on predicted strains that will circulate in the upcoming season. Influenza virus still causes significant health problems worldwide due to the low vaccine efficacy from unexpected outbreaks of next epidemic strains or the emergence of pandemic viruses. Current influenza vaccines are based on immunity to the hemagglutinin antigen that is highly variable among different influenza viruses circulating in humans and animals. Several scientific advances have been endeavored to develop universal vaccines that will induce broad protection. Universal vaccines have been focused on regions of viral proteins that are highly conserved across different virus subtypes. The strategies of universal vaccines include the matrix 2 protein, the hemagglutinin HA2 stalk domain, and T cell-based multivalent antigens. Supplemented and/or adjuvanted vaccination in combination with universal target antigenic vaccines would have much promise. This review summarizes encouraging scientific advances in the field with a focus on novel vaccine designs. PMID:24427759

Lee, Young-Tae; Kim, Ki-Hye; Ko, Eun-Ju; Lee, Yu-Na; Kim, Min-Chul; Kwon, Young-Man; Tang, Yinghua; Cho, Min-Kyoung; Lee, Youn-Jeong

2014-01-01

149

Enteric Immunization of Mice Against Influenza with Recombinant Vaccinia  

NASA Astrophysics Data System (ADS)

Intrajejunal administration to mice of a recombinant vaccinia virus containing the influenza virus hemagglutinin gene induced IgA antibody in nasal, gut, and vaginal secretions. It also induced IgG antibody in serum and cell-mediated immunity. The immunization provided significant protection against an influenza virus challenge. This work suggests that enteric-coated recombinant vaccinia could be an orally administered, inexpensive, multivalent, temperature-stable, safe, and effective vaccine for children that could be particularly useful in developing nations, where multiple injections are not easily administered. Oral administration of vaccines should also reduce children's fear of shots at the doctor's office.

Meitin, Catherine A.; Bender, Bradley S.; Small, Parker A., Jr.

1994-11-01

150

Phosphorylation of dGMP analogs by vaccinia virus TMP kinase and human GMP kinase.  

PubMed

Vaccinia virus thymidylate kinase, although similar in sequence to human TMP kinase, has broader substrate specificity and phosphorylates (E)-5-(2-bromovinyl)-dUMP and dGMP. Modified guanines such as glyoxal-dG, 8-oxo-dG, O(6)-methyl-dG, N(2)-ethyl-dG and N(7)-methyl-dG were found present in cancer cell DNA. Alkylated and oxidized dGMP analogs were examined as potential substrates for vaccinia TMP kinase and also for human TMP and GMP kinases. Molecular models obtained from structure-based docking rationalized the enzymatic data. All tested nucleotides are found surprisingly substrates of vaccinia TMP kinase and also of human GMP kinase. Interestingly, O(6)-methyl-dGMP is the only analog specific for the vaccinia enzyme. Thus, O(6)-Me-dGMP could be useful for designing new compounds of medical interest either in antipoxvirus therapy or in experimental combined gene/chemotherapy of cancer. These results also provide new insights regarding dGMP analog reaction with human GMP kinase and their slow recycling by salvage pathway nucleotide kinases. PMID:19631609

Auvynet, Constance; Topalis, Dimitri; Caillat, Christophe; Munier-Lehmann, Hélčne; Seclaman, Edward; Balzarini, Jan; Agrofoglio, Luigi André; Kaminski, Pierre Alexandre; Meyer, Philippe; Deville-Bonne, Dominique; El Amri, Chahrazade

2009-10-01

151

Vaccinia reporter viruses for quantifying viral function at all stages of gene expression.  

PubMed

Poxviruses are a family of double stranded DNA viruses that include active human pathogens such as monkeypox, molluscum contagiousum, and Contagalo virus. The family also includes the smallpox virus, Variola. Due to the complexity of poxvirus replication, many questions still remain regarding their gene expression strategy. In this article we describe the conceptualization and usage of recombinant vaccinia viruses that enable real-time measurement of single and multiple stages of viral gene expression in a high-throughput format. This is enabled through the use of spectrally distinct fluorescent proteins as reporters for each of three stages of viral replication. These viruses provide a high signal-to-noise ratio while retaining stage specific expression patterns, enabling plate-based assays and microscopic observations of virus propagation and replication. These tools have uses for antiviral discovery, studies of the virus-host interaction, and evolutionary biology. PMID:24894622

Rozelle, Daniel K; Filone, Claire Marie; Dower, Ken; Connor, John H

2014-01-01

152

Reconstitution of carbonic anhydrase activity of the cell-surface-binding protein of vaccinia virus  

PubMed Central

The N-terminal region of a 32 kDa cell-surface-binding protein, encoded by the D8L gene of vaccinia virus, shows sequence homology to CAs (carbonic anhydrases; EC 4.2.1.1). The active CAs catalyse the reversible hydration of CO2 to bicarbonate participating in many physiological processes. The CA-like domain of vaccinia protein [vaccCA (vaccinia virus CA-like protein)] contains one of the three conserved histidine residues required for co-ordination to the catalytic zinc ion and for enzyme activity. In the present study, we report the engineering of catalytically active vaccCA mutants by introduction of the missing histidine residues into the wild-type protein. The wild-type vaccCA was inactive as a catalyst and does not bind sulfonamide CA inhibitors. Its position on a phylogram with other hCAs (human CAs) shows a relationship with the acatalytic isoforms CA X and XI, suggesting that the corresponding viral gene was acquired from the human genome by horizontal gene transfer. The single mutants (vaccCA N92H/Y69H) showed low enzyme activity and low affinity for acetazolamide, a classical sulfonamide CA inhibitor. The activity of the double mutant, vaccCA N92H/Y69H, was much higher, of the same order of magnitude as that of some human isoforms, namely CA VA and CA XII. Moreover, its affinity for acetazolamide was high, comparable with that of the most efficient human isoenzyme, CA II (in the low nanomolar range). Multiplication of vaccinia virus in HeLa cells transfected with the vaccCA N92H/Y69H double mutant was approx. 2-fold more efficient than in wild-type vaccCA transfectants, suggesting that the reconstitution of the enzyme activity improved the virus life cycle. PMID:17614791

Ohradanova, Anna; Vullo, Daniela; Kopacek, Juraj; Temperini, Claudia; Betakova, Tatiana; Pastorekova, Silvia; Pastorek, Jaromir; Supuran, Claudiu T.

2007-01-01

153

Advances in virus research  

SciTech Connect

This book contains eight chapters. Some of the titles are: Initiation of viral DNA replication; Vaccinia: virus, vector, vaccine; The pre-S region of hepadnavirus envelope proteins; and Archaebacterial viruses.

Maramorosch, K. (Rutgers--the State Univ., New Brunswick, NJ (USA)); Murphy, F.A. (Centers for Disease Control, Atlanta, GA (USA)); Shatkin, A.J. (Rutgers-UMDNJ, Piscataway, NJ (US))

1988-01-01

154

Human Vaccines & Immunotherapeutics: News  

PubMed Central

Oncolytic vaccinia virus vaccine: Promising in liver cancer patients FDA panel endorses quadrivalent influenza vaccines Approval for the first meningitis B vaccine Stallergenes seeks FDA approval for sublingual grass-pollen allergy tablet Live-attenuated dengue vaccine promising in Phase 1 GAVI funds HPV vaccines for girls in developing countries First human trials for new superantigen bioterrorism vaccine Hexyon hexavalent pediatric vaccine recommended for approval

Riedmann, Eva M.

2013-01-01

155

Vaccination of chimpanzees against infection by the hepatitis C virus.  

PubMed Central

A high incidence of community-acquired hepatitis C virus infection that can lead to the progressive development of chronic active hepatitis, liver cirrhosis, and primary hepatocellular carcinoma occurs throughout the world. A vaccine to control the spread of this agent that represents a major cause of chronic liver disease is therefore needed. Seven chimpanzees (Pan troglodytes) have been immunized with both putative envelope glycoproteins [E1 (gp33) and E2 (gp72)] that were copurified from HeLa cells infected with a recombinant vaccinia virus expression vector. Despite the induction of a weak humoral immune response to these viral glycoproteins in experimentally infected chimpanzees, a strong humoral immune response was obtained in all vaccines. The five highest responders showed complete protection against an i.v. challenge with homologous hepatitis C virus 1. The remaining two vaccines became infected, but both infection and disease may have been ameliorated in comparison with four similarly challenged control chimpanzees, all of which developed acute hepatitis and chronic infections. These results provide considerable encouragement for the eventual control of hepatitis C virus infection by vaccination. PMID:7509068

Choo, Q L; Kuo, G; Ralston, R; Weiner, A; Chien, D; Van Nest, G; Han, J; Berger, K; Thudium, K; Kuo, C

1994-01-01

156

Modified vaccinia virus Ankara expressing the hemagglutinin of pandemic (H1N1) 2009 virus induces cross-protective immunity against Eurasian 'avian-like' H1N1 swine viruses in mice  

PubMed Central

Objectives To examine cross-reactivity between hemagglutinin (HA) derived from A/California/7/09 (CA/09) virus and that derived from representative Eurasian “avian-like” (EA) H1N1 swine viruses isolated in Italy between 1999 and 2008 during virological surveillance in pigs. Design Modified vaccinia virus Ankara (MVA) expressing the HA gene of CA/09 virus (MVA-HA-CA/09) was used as a vaccine to investigate cross-protective immunity against H1N1 swine viruses in mice. Sample Two classical swine H1N1 (CS) viruses and four representative EA-like H1N1 swine viruses previously isolated during outbreaks of respiratory disease in pigs on farms in Northern Italy were used in this study. Setting Female C57BL/6 mice were vaccinated with MVA/HA/CA/09 and then challenged intranasally with H1N1 swine viruses. Main outcome measures Cross-reactive antibody responses were determined by hemagglutination- inhibition (HI) and virus microneutralizing (MN) assays of sera from MVA-vaccinated mice. The extent of protective immunity against infection with H1N1 swine viruses was determined by measuring lung viral load on days 2 and 4 post-challenge. Results and Conclusions Systemic immunization of mice with CA/09-derived HA, vectored by MVA, elicited cross-protective immunity against recent EA-like swine viruses. This immune protection was related to the levels of cross-reactive HI antibodies in the sera of the immunized mice and was dependent on the similarity of the antigenic site Sa of H1 HAs. Our findings suggest that the herd immunity elicited in humans by the pandemic (H1N1) 2009 virus could limit the transmission of recent EA-like swine HA genes into the influenza A virus gene pool in humans. PMID:24373385

Castrucci, Maria R; Facchini, Marzia; Di Mario, Giuseppina; Garulli, Bruno; Sciaraffia, Ester; Meola, Monica; Fabiani, Concetta; De Marco, Maria A; Cordioli, Paolo; Siccardi, Antonio; Kawaoka, Yoshihiro; Donatelli, Isabella

2014-01-01

157

Vaccinia virus, herpes simplex virus, and carcinogens induce DNA amplification in a human cell line and support replication of a helpervirus dependent parvovirus  

SciTech Connect

The SV40-transformed human kidney cell line, NB-E, amplifies integrated as well as episomal SV40 DNA upon treatment with chemical (DMBA) or physical (uv irradiation) carcinogens (initiators) as well as after infection with herpes simplex virus (HSV) type 1 or with vaccinia virus. In addition it is shown that vaccinia virus induces SV40 DNA amplification also in the SV40-transformed Chinese hamster embryo cell line, CO631. These findings demonstrate that human cells similar to Chinese hamster cells amplify integrated DNA sequences after treatment with carcinogens or infection with specific viruses. Furthermore, a poxvirus--vaccinia virus--similar to herpes group viruses induces DNA amplification. As reported for other systems, the vaccinia virus-induced DNA amplification in NB-E cells is inhibited by coinfection with adeno-associated virus (AAV) type 5. This is in line with previous studies on inhibition of carcinogen- or HSV-induced DNA amplification in CO631 cells. The experiments also demonstrate that vaccinia virus, in addition to herpes and adenoviruses acts as a helper virus for replication and structural antigen synthesis of AAV-5 in NB-E cells.

Schlehofer, J.R.; Ehrbar, M.; zur Hausen, H.

1986-07-15

158

Elevated Expression Levels of Inhibitory Receptor Programmed Death 1 on Simian Immunodeficiency Virus-Specific CD8 T Cells during Chronic Infection but Not after Vaccination  

Microsoft Academic Search

Here, we study the temporal expression of the inhibitory receptor programmed death 1 (PD-1) on simian immunodeficiency virus (SIV) Gag-specific T cells following pathogenic SIV infection or following vaccination with a DNA\\/modified vaccinia virus Ankara (DNA\\/MVA) vaccine and simian\\/human immunodeficiency virus (SHIV) challenge in macaques. Following infection, the majority (>95%) of Gag-specific CD8 T cells expressed PD-1, and the level

Vijayakumar Velu; Sunil Kannanganat; Chris Ibegbu; Lakshmi Chennareddi; Francois Villinger; Gordon J. Freeman; Rafi Ahmed; Rama Rao Amara

2007-01-01

159

ISG15 Is Counteracted by Vaccinia Virus E3 Protein and Controls the Proinflammatory Response against Viral Infection  

PubMed Central

Conjugation of ISG15 inhibits replication of several viruses. Here, using an expression system for assaying human and mouse ISG15 conjugations (ISGylations), we have demonstrated that vaccinia virus E3 protein binds and antagonizes human and mouse ISG15 modification. To study ISGylation importance in poxvirus infection, we used a mouse model that expresses deconjugating proteases. Our results indicate that ISGylation restricts in vitro replication of the vaccinia virus VV?E3L mutant but unconjugated ISG15 is crucial to counteract the inflammatory response produced after VV?E3L infection. PMID:24257616

Eduardo-Correia, Benedito; Martinez-Romero, Carles; Garcia-Sastre, Adolfo

2014-01-01

160

Genome-wide analysis of vaccinia virus proteinprotein interactions  

E-print Network

as the smallpox vaccine, has gained popularity as a mammalian expression vector, and is being tested of smallpox, monkeypox, and molluscum contagiosum (10), as well as insights into many areas of molecular

Dunham, Maitreya

161

Preclinical Evaluation of Oncolytic Vaccinia Virus for Therapy of Canine Soft Tissue Sarcoma  

PubMed Central

Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for canine cancer therapy. In this study we describe the establishment of an in vivo model of canine soft tissue sarcoma (CSTS) using the new isolated cell line STSA-1 and the analysis of the virus-mediated oncolytic and immunological effects of two different Lister VACV LIVP1.1.1 and GLV-1h68 strains against CSTS. Cell culture data demonstrated that both tested VACV strains efficiently infected and destroyed cells of the canine soft tissue sarcoma line STSA-1. In addition, in our new canine sarcoma tumor xenograft mouse model, systemic administration of LIVP1.1.1 or GLV-1h68 viruses led to significant inhibition of tumor growth compared to control mice. Furthermore, LIVP1.1.1 mediated therapy resulted in almost complete tumor regression and resulted in long-term survival of sarcoma-bearing mice. The replication of the tested VACV strains in tumor tissues led to strong oncolytic effects accompanied by an intense intratumoral infiltration of host immune cells, mainly neutrophils. These findings suggest that the direct viral oncolysis of tumor cells and the virus-dependent activation of tumor-associated host immune cells could be crucial parts of anti-tumor mechanism in STSA-1 xenografts. In summary, the data showed that both tested vaccinia virus strains and especially LIVP1.1.1 have great potential for effective treatment of CSTS. PMID:22615950

Josupeit, Rafael; Rudolph, Stephan; Ehrig, Klaas; Donat, Ulrike; Weibel, Stephanie; Chen, Nanhai G.; Yu, Yong A.; Zhang, Qian; Heisig, Martin; Thamm, Douglas; Stritzker, Jochen; MacNeill, Amy; Szalay, Aladar A.

2012-01-01

162

Vaccinia virus-expressed bovine ephemeral fever virus G but not G(NS) glycoprotein induces neutralizing antibodies and protects against experimental infection.  

PubMed

Two related glycoproteins (G and G(NS)) encoded in the bovine ephemeral fever virus (BEFV) genome were expressed from recombinant vaccinia viruses (rVV). Both proteins were detected in lysates of rVV-infected cells by labelling with D-[6-3H]glucosamine or by immuno-blotting. The recombinant G protein (mol. mass 79 kDa) appeared slightly smaller than the native G protein but reacted with monoclonal antibodies directed against all defined neutralizing antigenic sites (G1, G2, G3a, G3b and G4). The recombinant G(NS) protein (mol. mass 90kDa) was identical in size to the native G(NS) protein and failed to react by immuno-fluorescence with anti-G protein monoclonal or poly-clonal antibodies. Antisera raised in rabbits against rVV-G or rVV-G(NS) both reacted strongly by immuno-fluorescence and immuno-electron microscopy with BEFV-infected cells. The G protein was localized intracellularly in the endoplasmic reticulum/Golgi complex and at the cell surface associated with budding and mature virus particles. The G(NS) protein also localized intracellularly in the endoplasmic reticulum/Golgi complex; however, at the cell surface it was associated with amorphous structures and not with budding or mature virions. Rabbits vaccinated with rVV-G developed high levels of antibodies which neutralized BEFV grown in either mammalian or insect cells. Cattle vaccinated with rVV-G also produced neutralizing antibodies and were protected against experimental BEFV infection. In contrast, rVV-G(NS) vaccinated rabbits and cattle failed to produce neutralizing antibodies and, after challenge, BEFV was isolated from two-thirds of the vaccinated cattle. PMID:8627251

Hertig, C; Pye, A D; Hyatt, A D; Davis, S S; McWilliam, S M; Heine, H G; Walker, P J; Boyle, D B

1996-04-01

163

Distinct Gene Expression Profiles in Peripheral Blood Mononuclear Cells from Patients Infected with Vaccinia Virus, Yellow Fever 17D Virus, or Upper Respiratory Infections Running Title: PBMC Expression Response to Viral Agents  

PubMed Central

Gene expression in human peripheral blood mononuclear cells was systematically evaluated following smallpox and yellow fever vaccination, and naturally occurring upper respiratory infection (URI). All three infections were characterized by the induction of many interferon stimulated genes, as well as enhanced expression of genes involved in proteolysis and antigen presentation. Vaccinia infection was also characterized by a distinct expression signature composed of up-regulation of monocyte response genes, with repression of genes expressed by B and T-cells. In contrast, the yellow fever host response was characterized by a suppression of ribosomal and translation factors, distinguishing this infection from vaccinia and URI. No significant URI-specific signature was observed, perhaps reflecting greater heterogeneity in the study population and etiological agents. Taken together, these data suggest that specific host gene expression signatures may be identified that distinguish one or a small number of virus agents. PMID:17651872

Scherer, Christina A.; Magness, Charles L.; Steiger, Kathryn V.; Poitinger, Nicholas D.; Caputo, Christine M.; Miner, Douglas G.; Winokur, Patricia L.; Klinzman, Donna; McKee, Janice; Pilar, Christine; Ward, Patricia A.; Gillham, Martha H.; Haulman, N. Jean; Stapleton, Jack T.; Iadonato, Shawn P.

2007-01-01

164

Immunogenicity and protective efficacy of Semliki forest virus replicon-based DNA vaccines encoding goatpox virus structural proteins  

SciTech Connect

Goatpox, caused by goatpox virus (GTPV), is an acute feverish and contagious disease in goats often associated with high morbidity and high mortality. To resolve potential safety risks and vaccination side effects of existing live attenuated goatpox vaccine (AV41), two Semliki forest virus (SFV) replicon-based bicistronic expression DNA vaccines (pCSm-AAL and pCSm-BAA) which encode GTPV structural proteins corresponding to the Vaccinia virus proteins A27, L1, A33, and B5, respectively, were constructed. Then, theirs ability to induce humoral and cellular response in mice and goats, and protect goats against virulent virus challenge were evaluated. The results showed that, vaccination with pCSm-AAL and pCSm-BAA in combination could elicit strong humoral and cellular responses in mice and goats, provide partial protection against viral challenge in goats, and reduce disease symptoms. Additionally, priming vaccination with the above-mentioned DNA vaccines could significantly reduce the goats' side reactions from boosting vaccinations with current live vaccine (AV41), which include skin lesions at the inoculation site and fevers. Data obtained in this study could not only facilitate improvement of the current goatpox vaccination strategy, but also provide valuable guidance to suitable candidates for evaluation and development of orthopoxvirus vaccines.

Zheng Min [Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun 130062 (China); Guangxi Center for Animal Disease Control and Prevention, Nanning 530001 (China); College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062 (China); Jin Ningyi, E-mail: jinningyi2000@yahoo.com.c [Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun 130062 (China); Liu Qi, E-mail: gx_liuqi@yahoo.com.c [Guangxi Center for Animal Disease Control and Prevention, Nanning 530001 (China); Huo Xiaowei [Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun 130062 (China); Li Yang [Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun 130062 (China); College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062 (China); Hu Bo; Ma Haili; Zhu Zhanbo; Cong Yanzhao; Li Xiao; Jin Minglan; Zhu Guangze [Genetic Engineering Laboratory of PLA, Academy of Military Medical Sciences of PLA, Changchun 130062 (China)

2009-08-15

165

Molecular cloning, encoding sequence, and expression of vaccinia virus nucleic acid-dependent nucleoside triphosphatase gene.  

PubMed Central

A rabbit poxvirus genomic library contained within the expression vector lambda gt11 was screened with polyclonal antiserum prepared against vaccinia virus nucleic acid-dependent nucleoside triphosphatase (NTPase)-I enzyme. Five positive phage clones containing from 0.72- to 2.5-kilobase-pair (kbp) inserts expressed a beta-galactosidase fusion protein that was reactive by immunoblotting with the NTPase-I antibody. Hybridization analysis allowed the location of this gene within the vaccinia HindIIID restriction fragment. From the known nucleotide sequence of the 16-kbp vaccinia HindIIID fragment, we identified a region that contains a 1896-base open reading frame coding for a 631-amino acid protein. Analysis of the complete sequence revealed a highly basic protein, with hydrophilic COOH and NH2 termini, various hydrophobic domains, and no significant homology to other known proteins. Translational studies demonstrate that NTPase-I belongs to a late class of viral genes. This protein is highly conserved among Orthopoxviruses. Images PMID:3025846

Rodriguez, J F; Kahn, J S; Esteban, M

1986-01-01

166

Whole Cell Cryo-Electron Tomography Reveals Distinct Disassembly Intermediates of Vaccinia Virus  

PubMed Central

At each round of infection, viruses fall apart to release their genome for replication, and then reassemble into stable particles within the same host cell. For most viruses, the structural details that underlie these disassembly and assembly reactions are poorly understood. Cryo-electron tomography (cryo-ET), a unique method to investigate large and asymmetric structures at the near molecular resolution, was previously used to study the complex structure of vaccinia virus (VV). Here we study the disassembly of VV by cryo-ET on intact, rapidly frozen, mammalian cells, infected for up to 60 minutes. Binding to the cell surface induced distinct structural rearrangements of the core, such as a shape change, the rearrangement of its surface spikes and de-condensation of the viral DNA. We propose that the cell surface induced changes, in particular the decondensation of the viral genome, are a prerequisite for the subsequent release of the vaccinia DNA into the cytoplasm, which is followed by its cytoplasmic replication. Generally, this is the first study that employs whole cell cryo-ET to address structural details of pathogen-host cell interaction. PMID:17487274

Cyrklaff, Marek; Linaroudis, Alexandros; Boicu, Marius; Chlanda, Petr; Baumeister, Wolfgang; Griffiths, Gareth; Krijnse-Locker, Jacomine

2007-01-01

167

Inhibition of Vaccinia virus entry by a broad spectrum antiviral peptide  

SciTech Connect

Concerns about the possible use of Variola virus, the causative agent of smallpox, as a weapon for bioterrorism have led to renewed efforts to identify new antivirals against orthopoxviruses. We identified a peptide, EB, which inhibited infection by Vaccinia virus with an EC{sub 50} of 15 muM. A control peptide, EBX, identical in composition to EB but differing in sequence, was inactive (EC{sub 50} > 200 muM), indicating sequence specificity. The inhibition was reversed upon removal of the peptide, and EB treatment had no effect on the physical integrity of virus particles as determined by electron microscopy. Viral adsorption was unaffected by the presence of EB, and the addition of EB post-entry had no effect on viral titers or on early gene expression. The addition of EB post-adsorption resulted in the inhibition of beta-galactosidase expression from an early viral promoter with an EC{sub 50} of 45 muM. A significant reduction in virus entry was detected in the presence of the peptide when the number of viral cores released into the cytoplasm was quantified. Electron microscopy indicated that 88% of the virions remained on the surface of cells in the presence of EB, compared to 37% in the control (p < 0.001). EB also blocked fusion-from-within, suggesting that virus infection is inhibited at the fusion step. Analysis of EB derivatives suggested that peptide length may be important for the activity of EB. The EB peptide is, to our knowledge, the first known small molecule inhibitor of Vaccinia virus entry.

Altmann, S.E.; Jones, J.C. [Microbiology Doctoral Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706 (United States); Schultz-Cherry, S. [Microbiology Doctoral Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706 (United States); Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706 (United States); Brandt, C.R., E-mail: crbrandt@wisc.ed [Microbiology Doctoral Training Program, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706 (United States); Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706 (United States); Department of Medical Microbiology and Immunology, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706 (United States)

2009-06-05

168

CD40 ligand and tdTomato-armed vaccinia virus for induction of antitumor immune response and tumor imaging.  

PubMed

Oncolytic vaccinia virus is an attractive platform for immunotherapy. Oncolysis releases tumor antigens and provides co-stimulatory danger signals. However, arming the virus can improve efficacy further. CD40 ligand (CD40L, CD154) can induce apoptosis of tumor cells and it also triggers several immune mechanisms. One of these is a T-helper type 1 (Th1) response that leads to activation of cytotoxic T-cells and reduction of immune suppression. Therefore, we constructed an oncolytic vaccinia virus expressing hCD40L (vvdd-hCD40L-tdTomato), which in addition features a cDNA expressing the tdTomato fluorochrome for detection of virus, potentially important for biosafety evaluation. We show effective expression of functional CD40L both in vitro and in vivo. In a xenograft model of bladder carcinoma sensitive to CD40L treatment, we show that growth of tumors was significantly inhibited by the oncolysis and apoptosis following both intravenous and intratumoral administration. In a CD40-negative model, CD40L expression did not add potency to vaccinia oncolysis. Tumors treated with vvdd-mCD40L-tdtomato showed enhanced efficacy in a syngenic mouse model and induced recruitment of antigen-presenting cells and lymphocytes at the tumor site. In summary, oncolytic vaccinia virus coding for CD40L mediates multiple antitumor effects including oncolysis, apoptosis and induction of Th1 type T-cell responses. PMID:24305418

Parviainen, S; Ahonen, M; Diaconu, I; Hirvinen, M; Karttunen, Ĺ; Vähä-Koskela, M; Hemminki, A; Cerullo, V

2014-02-01

169

Structural and Biochemical Characterization of the Vaccinia Virus Envelope Protein D8 and Its Recognition by the Antibody LA5  

PubMed Central

Smallpox vaccine is considered a gold standard of vaccines, as it is the only one that has led to the complete eradication of an infectious disease from the human population. B cell responses are critical for the protective immunity induced by the vaccine, yet their targeted epitopes recognized in humans remain poorly described. Here we describe the biochemical and structural characterization of one of the immunodominant vaccinia virus (VACV) antigens, D8, and its binding to the monoclonal antibody LA5, which is capable of neutralizing VACV in the presence of complement. The full-length D8 ectodomain was found to form a tetramer. We determined the crystal structure of the LA5 Fab-monomeric D8 complex at a resolution of 2.1 Ĺ, as well as the unliganded structures of D8 and LA5-Fab at resolutions of 1.42 Ĺ and 1.6 Ĺ, respectively. D8 features a carbonic anhydrase (CAH) fold that has evolved to bind to the glycosaminoglycan (GAG) chondroitin sulfate (CS) on host cells. The central positively charged crevice of D8 was predicted to be the CS binding site by automated docking experiments. Furthermore, sequence alignment of various poxvirus D8 orthologs revealed that this crevice is structurally conserved. The D8 epitope is formed by 23 discontinuous residues that are spread across 80% of the D8 protein sequence. Interestingly, LA5 binds with a high-affinity lock-and-key mechanism above this crevice with an unusually large antibody-antigen interface, burying 2,434 Ĺ2 of protein surface. PMID:22623786

Matho, Michael H.; Maybeno, Matt; Benhnia, Mohammed Rafii-El-Idrissi; Becker, Danielle; Meng, Xiangzhi; Xiang, Yan; Crotty, Shane; Peters, Bjoern

2012-01-01

170

Transmission of vaccinia virus, possibly through sexual contact, to a woman at high risk for adverse complications.  

PubMed

Severe adverse events, including eczema vaccinatum (EV), can result after smallpox vaccination. Persons at risk for EV include those with underlying dermatologic conditions, such as atopic dermatitis. We investigated a case of vaccinia infection, possibly acquired during sexual contact with a recently vaccinated military service member, in a female Maryland resident with atopic dermatitis. The U.S. Department of Defense's Vaccine Healthcare Centers Network (VHCN) and the Centers for Disease Control and Prevention (CDC) worked in conjunction with the patient's physician and the Maryland Department of Health and Mental Hygiene (DHMH) to confirm the diagnosis, ensure treatment, and prevent further transmission. Specimens collected from the patient were tested at the DHMH laboratories and were positive by real-time polymerase chain reaction for nonvariola orthopoxvirus. Testing at the CDC verified the presence of vaccinia-specific DNA signatures. Continuing spread of the patient's lesions led to the administration of vaccinia immune globulin and strict infection control measures to prevent tertiary transmission to vulnerable family members, also with atopic dermatitis. VHCN contacted the service member to reinforce vaccination site care and hygiene. This case underscores the importance of prevaccination education for those receiving the smallpox vaccine to protect contacts at risk for developing severe adverse reactions. PMID:24306023

Said, Maria A; Haile, Charles; Palabindala, Venkataraman; Barker, Naomi; Myers, Robert; Thompson, Ruth; Wilson, Lucy; Allan-Martinez, Frances; Montgomery, Jay; Monroe, Benjamin; Tack, Danielle; Reynolds, Mary; Damon, Inger; Blythe, David

2013-12-01

171

Molecular genetic analysis of a vaccinia virus gene with an essential role in DNA replication  

SciTech Connect

The poxvirus, vaccinia, is large DNA virus which replicates in the cytoplasma of the host cell. The virus is believed to encode most or all of the functions required for the temporally regulated transcription and replication of its 186 kilobase genome. Physical and genetic autonomy from the host make vaccinia a useful eukaryotic organism in which to study replication genes and proteins, using a combination of biochemical and genetic techniques. Essential viral functions for replication are identified by conditional lethal mutants that fail to synthesize DNA at the non-permissive temperatures. One such group contains the non-complementing alleles ts17, ts24, ts69 (WR strain). Studies were undertaken to define the phenotype of ts mutants, and to identify and characterize the affected gene and protein. Mutant infection was essentially normal at 32{degree}C, but at 39{degree}C the mutants did not incorporate {sup 3}H-thymidine into nascent viral DNA or synthesize late viral proteins. If mutant cultures were shifted to non-permissive conditions at the height of replication, DNA synthesis was halted rapidly, implying that the mutants are defective in DNA elongation. The gene affected in the WR mutants and in ts6389, a DNA-minus mutant of the IHD strain, was mapped by marker rescue and corresponds to open reading frame 5 (orfD5) of the viral HindIII D fragment.

Evans, E.V.A.

1989-01-01

172

Respiratory syncytial virus vaccine development  

PubMed Central

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral disease in infants and young children. Presently, there are no explicit recommendations for RSV treatment apart from supportive care. The virus is therefore responsible for an estimated 160,000 deaths per year worldwide. Despite half a century of dedicated research, there remains no licensed vaccine product. Herein are described past and current efforts to harness innate and adaptive immune potentials to combat RSV. A plethora of candidate vaccine products and strategies are reviewed. The development of a successful RSV vaccine may ultimately stem from attention to historical lessons, in concert with an integral partnering of immunology and virology research fields. PMID:21988307

Hurwitz, Julia L

2011-01-01

173

Protective efficacy of several vaccines against highly pathogenic H5N1 avian influenza virus under experimental conditions.  

PubMed

Although several vaccines have been developed to protect against highly pathogenic avian influenza of subtype H5N1 'Asia' their efficiency has primarily been assessed individually. Thus, a direct comparison of their performance is still lacking. The following study was conducted to compare the protective efficacy of three commercially available inactivated vaccines based on influenza virus strains of subtypes H5N2 (vaccine A), H5N9 (vaccine B), and H5N3 (vaccine C), as well as two hemagglutinin expressing experimental vector vaccines (modified vaccinia virus Ankara-H5 and Newcastle disease virus-H5) against a lethal dose of highly pathogenic H5N1 avian influenza virus in chickens. To assess their potential as emergency vaccines, a single immunisation was performed for all vaccines, despite the recommendation of a double-vaccination schedule for commercial vaccines B and C. Overall, all vaccines induced clinical protection against challenge infection 3 weeks after immunisation. No mortality was observed in chickens immunised with vaccine A and viral shedding could not be detected. Immunisation with NDV-H5, vaccine C and MVA-H5 conferred also protection against lethal challenge. However, viral RNA was detected by real-time RT-PCR in swabs of 10%, 20% and 50% of animals, and 0%, 10% and 30% of animals, respectively, shed infectious virus. Immunisation with vaccine B was less protective since 50% of the vaccinated animals shed infectious virus after challenge and 20% of the chickens succumbed to disease. These results indicate that the NDV-H5 vectored vaccine is similarly effective as the best inactivated vaccine. Considering the advantage of live NDV which can be administered via spray or drinking water as well as the potential use of this H5 expressing vector vaccine for an easy DIVA (differentiating infected from vaccinated animals) strategy, NDV-H5 could represent an alternative for extensive vaccination against avian influenza in chickens. PMID:18291561

Veits, Jutta; Römer-Oberdörfer, Angela; Helferich, Dorothee; Durban, Markus; Suezer, Yasemin; Sutter, Gerd; Mettenleiter, Thomas C

2008-03-20

174

Highly attenuated modified vaccinia virus Ankara replicates in baby hamster kidney cells, a potential host for virus propagation, but not in various human transformed and primary cells  

Microsoft Academic Search

Although desirable for safety reasons, the host range restrictions of modified vaccinia virus Ankara (MVA) make it less applicable for general use. Propagation in primary chicken embryo fibroblasts (CEF) requires particular cell culture experience and has no pre-established record of tissue culture reproducibility. We investigated a variety of estab- lished cell lines for productive virus growth and recombinant gene expression.

Ingo Drexler; Karl Heller; Britta Wahren; Volker Erfle; Gerd Sutter

175

Expression of the highly conserved vaccinia virus E6 protein is required for virion morphogenesis  

SciTech Connect

The vaccinia virus E6R gene (VACVWR062) is conserved in all members of the poxvirus family and encodes a protein associated with the mature virion. We confirmed this association and provided evidence for an internal location. An inducible mutant that conditionally expresses E6 was constructed. In the absence of inducer, plaque formation and virus production were severely inhibited in several cell lines, whereas some replication occurred in others. This difference could be due to variation in the stringency of repression, since we could not isolate a stable deletion mutant even in the more 'permissive' cells. Under non-permissive conditions, viral late proteins were synthesized but processing of core proteins was inefficient, indicative of an assembly block. Transmission electron microscopy of sections of cells infected with the mutant in the absence of inducer revealed morphogenetic defects with crescents and empty immature virions adjacent to dense inclusions of viroplasm. Mature virions were infrequent and cores appeared to have lucent centers.

Resch, Wolfgang; Weisberg, Andrea S. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3210 (United States); Moss, Bernard, E-mail: bmoss@nih.go [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3210 (United States)

2009-04-10

176

The E6 protein from vaccinia virus is required for the formation of immature virions  

SciTech Connect

An IPTG-inducible mutant in the E6R gene of vaccinia virus was used to study the role of the E6 virion core protein in viral replication. In the absence of the inducer, the mutant exhibited a normal pattern DNA replication, concatemer resolution and late gene expression, but it showed an inhibition of virion structural protein processing it failed to produce infectious particles. Electron microscopic analysis showed that in the absence of IPTG viral morphogenesis was arrested before IV formation: crescents, aberrant or empty IV-like structures, and large aggregated virosomes were observed throughout the cytoplasm. The addition of IPTG to release a 12-h block showed that virus infectious particles could be formed in the absence of de novo DNA synthesis. Our observations show that in the absence of E6 the association of viroplasm with viral membrane crescents is impaired.

Boyd, Olga; Turner, Peter C.; Moyer, Richard W.; Condit, Richard C. [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States); Moussatche, Nissin, E-mail: nissin@ufl.ed [Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610 (United States)

2010-04-10

177

PERSPECTIVES E Evaluation in Nonhuman Primates of Vaccines against Ebola Virus  

E-print Network

Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90 % of cases in both humans and nonhuman primates. No vaccines or treatments are available for human use. We evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal EBOV infection. The following immunogens were used: RNA replicon particles derived from an attenuated strain of Venezuelan equine encephalitis virus (VEEV) expressing EBOV glycoprotein and nucleoprotein; recombinant Vaccinia virus expressing EBOV glycoprotein; liposomes containing lipid A and inactivated EBOV; and a concentrated, inactivated whole-virion preparation. None of these strategies successfully protected nonhuman primates from robust challenge with EBOV. The disease observed in primates differed from that in rodents, suggesting that rodent models of EBOV may not predict the efficacy of candidate vaccines in primates and that protection of primates may require different mechanisms.

Thomas W. Geisbert; Peter Pushko; Kevin Anderson; Jonathan Smith; Kelly J. Davis; Peter B. Jahrling

178

Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.  

National Technical Information Service (NTIS)

The dengue-l candidate vaccine (TP 56, nonmutagenized) and it parent virus were compared for their ability to infect orally Aedes aegypti and Aedes albopictus mosquitoes. The vaccine virus was as infective orally as the parent virus for both mosquito spec...

B. J. Beaty

1983-01-01

179

Comparative Analysis of Poxvirus Orthologues of the Vaccinia Virus E3 Protein: Modulation of Protein Kinase R Activity, Cytokine Responses, and Virus Pathogenicity?  

PubMed Central

Poxviruses are important human and animal pathogens that have evolved elaborate strategies for antagonizing host innate and adaptive immunity. The E3 protein of vaccinia virus, the prototypic member of the orthopoxviruses, functions as an inhibitor of innate immune signaling and is essential for vaccinia virus replication in vivo and in many human cell culture systems. However, the function of orthologues of E3 expressed by poxviruses of other genera with different host specificity remains largely unknown. In the present study, we characterized the E3 orthologues from sheeppox virus, yaba monkey tumor virus, swinepox virus, and myxoma virus for their ability to modulate protein kinase R (PKR) function, cytokine responses and virus pathogenicity. We found that the E3 orthologues of myxoma virus and swinepox virus could suppress PKR activation and interferon (IFN)-induced antiviral activities and restore the host range function of E3 in HeLa cells. In contrast, the E3 orthologues from sheeppox virus and yaba monkey tumor virus were unable to inhibit PKR activation. While the sheeppox orthologue was unable to restore the host range function of E3, the yaba monkey tumor virus orthologue partially restored E3-deficient vaccinia virus replication in HeLa cells, correlated with its ability to suppress IFN-induced antiviral activities. Moreover, poxvirus E3 orthologues show varying ability to inhibit the induction of antiviral and proinflammatory cytokines. Despite these in vitro results, none of the E3 orthologues tested was capable of restoring pathogenicity to E3-deficient vaccinia virus in vivo. PMID:21917954

Myskiw, Chad; Arsenio, Janilyn; Hammett, Craig; van Bruggen, Rebekah; Deschambault, Yvon; Beausoleil, Nicole; Babiuk, Shawn; Cao, Jingxin

2011-01-01

180

Comparison of host cell gene expression in cowpox, monkeypox or vaccinia virus-infected cells reveals virus-specific regulation of immune response genes  

PubMed Central

Background Animal-borne orthopoxviruses, like monkeypox, vaccinia and the closely related cowpox virus, are all capable of causing zoonotic infections in humans, representing a potential threat to human health. The disease caused by each virus differs in terms of symptoms and severity, but little is yet know about the reasons for these varying phenotypes. They may be explained by the unique repertoire of immune and host cell modulating factors encoded by each virus. In this study, we analysed the specific modulation of the host cell’s gene expression profile by cowpox, monkeypox and vaccinia virus infection. We aimed to identify mechanisms that are either common to orthopoxvirus infection or specific to certain orthopoxvirus species, allowing a more detailed description of differences in virus-host cell interactions between individual orthopoxviruses. To this end, we analysed changes in host cell gene expression of HeLa cells in response to infection with cowpox, monkeypox and vaccinia virus, using whole-genome gene expression microarrays, and compared these to each other and to non-infected cells. Results Despite a dominating non-responsiveness of cellular transcription towards orthopoxvirus infection, we could identify several clusters of infection-modulated genes. These clusters are either commonly regulated by orthopoxvirus infection or are uniquely regulated by infection with a specific orthopoxvirus, with major differences being observed in immune response genes. Most noticeable was an induction of genes involved in leukocyte migration and activation in cowpox and monkeypox virus-infected cells, which was not observed following vaccinia virus infection. Conclusion Despite their close genetic relationship, the expression profiles induced by infection with different orthopoxviruses vary significantly. It may be speculated that these differences at the cellular level contribute to the individual characteristics of cowpox, monkeypox and vaccinia virus infections in certain host species. PMID:23425254

2013-01-01

181

Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer.  

PubMed

We reported earlier the delivery of antiangiogenic single chain antibodies by using oncolytic vaccinia virus strains to enhance their therapeutic efficacy. Here, we provide evidence that gene-evoked production of melanin can be used as a therapeutic and diagnostic mediator, as exemplified by insertion of only one or two genes into the genome of an oncolytic vaccinia virus strain. We found that produced melanin is an excellent reporter for optical imaging without addition of substrate. Melanin production also facilitated deep tissue optoacoustic imaging as well as MRI. In addition, melanin was shown to be a suitable target for laser-induced thermotherapy and enhanced oncolytic viral therapy. In conclusion, melanin as a mediator for thermotherapy and reporter for different imaging modalities may soon become a versatile alternative to replace fluorescent proteins also in other biological systems. After ongoing extensive preclinical studies, melanin overproducing oncolytic virus strains might be used in clinical trials in patients with cancer. PMID:23401518

Stritzker, Jochen; Kirscher, Lorenz; Scadeng, Miriam; Deliolanis, Nikolaos C; Morscher, Stefan; Symvoulidis, Panagiotis; Schaefer, Karin; Zhang, Qian; Buckel, Lisa; Hess, Michael; Donat, Ulrike; Bradley, William G; Ntziachristos, Vasilis; Szalay, Aladar A

2013-02-26

182

Vaccinia virus-mediated melanin production allows MR and optoacoustic deep tissue imaging and laser-induced thermotherapy of cancer  

PubMed Central

We reported earlier the delivery of antiangiogenic single chain antibodies by using oncolytic vaccinia virus strains to enhance their therapeutic efficacy. Here, we provide evidence that gene-evoked production of melanin can be used as a therapeutic and diagnostic mediator, as exemplified by insertion of only one or two genes into the genome of an oncolytic vaccinia virus strain. We found that produced melanin is an excellent reporter for optical imaging without addition of substrate. Melanin production also facilitated deep tissue optoacoustic imaging as well as MRI. In addition, melanin was shown to be a suitable target for laser-induced thermotherapy and enhanced oncolytic viral therapy. In conclusion, melanin as a mediator for thermotherapy and reporter for different imaging modalities may soon become a versatile alternative to replace fluorescent proteins also in other biological systems. After ongoing extensive preclinical studies, melanin overproducing oncolytic virus strains might be used in clinical trials in patients with cancer. PMID:23401518

Stritzker, Jochen; Kirscher, Lorenz; Scadeng, Miriam; Deliolanis, Nikolaos C.; Morscher, Stefan; Symvoulidis, Panagiotis; Schaefer, Karin; Zhang, Qian; Buckel, Lisa; Hess, Michael; Donat, Ulrike; Bradley, William G.; Ntziachristos, Vasilis; Szalay, Aladar A.

2013-01-01

183

Significant Growth Inhibition of Canine Mammary Carcinoma Xenografts following Treatment with Oncolytic Vaccinia Virus GLV-1h68  

PubMed Central

Canine mammary carcinoma is a highly metastatic tumor that is poorly responsive to available treatment. Therefore, there is an urgent need to identify novel agents for therapy of this disease. Recently, we reported that the oncolytic vaccinia virus GLV-1h68 could be a useful tool for therapy of canine mammary adenoma in vivo. In this study we analyzed the therapeutic effect of GLV-1h68 against canine mammary carcinoma. Cell culture data demonstrated that GLV-1h68 efficiently infected and destroyed cells of the mammary carcinoma cell line MTH52c. Furthermore, after systemic administration, this attenuated vaccinia virus strain primarily replicated in canine tumor xenografts in nude mice. Finally, infection with GLV-1h68 led to strong inflammatory and oncolytic effects resulting in significant growth inhibition of the tumors. In summary, the data showed that the GLV-1h68 virus strain has promising potential for effective treatment of canine mammary carcinoma. PMID:20631910

Gentschev, Ivaylo; Ehrig, Klaas; Donat, Ulrike; Hess, Michael; Rudolph, Stephan; Chen, Nanhai; Yu, Yong A.; Zhang, Qian; Bullerdiek, Jörn; Nolte, Ingo; Stritzker, Jochen; Szalay, Aladar A.

2010-01-01

184

Silver nanoparticles inhibit vaccinia virus infection by preventing viral entry through a macropinocytosis-dependent mechanism.  

PubMed

Silver nanoparticles have been shown to inhibit viruses. However, very little is known about the mechanism of antiviral activity. This study tested the hypothesis that 25-nm silver nanoparticles inhibited Vaccinia virus replication by preventing viral entry. Plaque reduction, confocal microscopy, and beta-galactosidase reporter gene assays were used to examine viral attachment and entry in the presence and absence of silver nanoparticles. To explore the mechanism of inhibition, viral entry experiments were conducted with silver nanoparticles and small interfering RNAs designed to silence the gene coding for p21-activated kinase 1, a key mediator of macropinocytosis. The silver nanoparticles caused a 4- to 5-log reduction in viral titer at concentrations that were not toxic to cells. Virus was capable of adsorbing to cells but could not enter cells in the presence of silver nanoparticles. Virus particles that had adsorbed to cells in the presence of silver nanoparticles were found to be infectious upon removal from the cells, indicating lack of direct virucidal effect. The half maximal inhibitory concentration for viral entry in the presence of silver nanoparticles was 27.4+/-3.3 microg/ml. When macropinocytosis was blocked, this inhibition was significantly reduced. Thus, macropinocytosis was required for the full antiviral effect. For the first time, this study points to the novel result that a cellular process involved in viral entry is responsible for the antiviral effects of silver nanoparticles. PMID:23980510

Trefry, John C; Wooley, Dawn P

2013-09-01

185

Mutational analysis of vaccinia virus nucleoside triphosphate phosphohydrolase II, a DExH box RNA helicase.  

PubMed Central

Vaccinia virus nucleoside triphosphate phosphohydrolase II (NPH-II), a 3'-to-5' RNA helicase, displays sequence similarity to members of the DExH family of nucleic acid-dependent nucleoside triphosphatases (NTPases). The contributions of the conserved GxGKT and DExH motifs to enzyme activity were assessed by alanine scanning mutagenesis. Histidine-tagged versions of NPH-II were expressed in vaccinia virus-infected BSC40 cells and purified by nickel affinity and conventional fractionation steps. Wild-type His-NPH-II was indistinguishable from native NPH-II with respect to RNA helicase, RNA binding, and nucleic acid-stimulated NTPase activities. The K-191-->A (K191A), D296A, and E297A mutant proteins bound RNA as well as wild-type His-NPH-II did, but they were severely defective in NTPase and helicase functions. The H299A mutant was active in RNA binding and NTP hydrolysis but was defective in duplex unwinding. Whereas the NTPase of wild-type NPH-II was stimulated > 10-fold by polynucleotide cofactors, the NTPase of the H299A mutant was nucleic acid independent. Because the specific NTPase activity of the H299A mutant in the absence of nucleic acid was near that of wild-type enzyme in the presence of DNA or RNA and because the Km for ATP was unaltered by the H299A substitution, we regard this mutation as a "gain-of-function" mutation and suggest that the histidine residue in the DExH box is required to couple the NTPase and helicase activities. PMID:7609038

Gross, C H; Shuman, S

1995-01-01

186

Oncolytic Viruses as Anticancer Vaccines  

PubMed Central

Oncolytic virotherapy has shown impressive results in preclinical studies and first promising therapeutic outcomes in clinical trials as well. Since viruses are known for a long time as excellent vaccination agents, oncolytic viruses are now designed as novel anticancer agents combining the aspect of lysis-dependent cytoreductive activity with concomitant induction of antitumoral immune responses. Antitumoral immune activation by oncolytic virus infection of tumor tissue comprises both, immediate effects of innate immunity and also adaptive responses for long lasting antitumoral activity, which is regarded as the most prominent challenge in clinical oncology. To date, the complex effects of a viral tumor infection on the tumor microenvironment and the consequences for the tumor-infiltrating immune cell compartment are poorly understood. However, there is more and more evidence that a tumor infection by an oncolytic virus opens up a number of options for further immunomodulating interventions such as systemic chemotherapy, generic immunostimulating strategies, dendritic cell-based vaccines, and antigenic libraries to further support clinical efficacy of oncolytic virotherapy. PMID:25101244

Woller, Norman; Gurlevik, Engin; Ureche, Cristina-Ileana; Schumacher, Anja; Kuhnel, Florian

2014-01-01

187

Replication-defective viruses as vaccines and vaccine vectors Tim Dudek a,b  

E-print Network

, such as human immunodeficiency virus or herpes simplex virus. Therefore, new types of vaccines are needed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233 Herpes simplex virus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 Herpes simplex virus

Knipe, David M.

188

Multiserotype Protection Elicited by a Combinatorial Prime-Boost Vaccination Strategy against Bluetongue Virus  

PubMed Central

Bluetongue virus (BTV) belongs to the genus Orbivirus within the family Reoviridae. The development of vector-based vaccines expressing conserved protective antigens results in increased immune activation and could reduce the number of multiserotype vaccinations required, therefore providing a cost-effective product. Recent recombinant DNA technology has allowed the development of novel strategies to develop marker and safe vaccines against BTV. We have now engineered naked DNAs and recombinant modified vaccinia virus Ankara (rMVA) expressing VP2, VP7 and NS1 proteins from BTV-4. IFNAR(?/?) mice inoculated with DNA/rMVA-VP2,-VP7-NS1 in an heterologous prime boost vaccination strategy generated significant levels of antibodies specific of VP2, VP7, and NS1, including those with neutralizing activity against BTV-4. In addition, vaccination stimulated specific CD8+ T cell responses against these three BTV proteins. Importantly, the vaccine combination expressing NS1, VP2 and VP7 proteins of BTV-4, elicited sterile protection against a lethal dose of homologous BTV-4 infection. Remarkably, the vaccine induced cross-protection against lethal doses of heterologous BTV-8 and BTV-1 suggesting that the DNA/rMVA-VP2,-VP7,-NS1 marker vaccine is a promising multiserotype vaccine against BTV. PMID:22514660

Calvo-Pinilla, Eva; Navasa, Nicolas; Anguita, Juan; Ortego, Javier

2012-01-01

189

Cryo X-ray nano-tomography of vaccinia virus infected cells.  

PubMed

We have performed full-field cryo X-ray microscopy in the water window photon energy range on vaccinia virus (VACV) infected cells to produce tomographic reconstructions. PtK2 cells were infected with a GFP-expressing VACV strain and frozen by plunge fast freezing. The infected cells were selected by light fluorescence microscopy of the GFP marker and subsequently imaged in the X-ray microscope under cryogenic conditions. Tomographic tilt series of X-ray images were used to yield three-dimensional reconstructions showing different cell organelles (nuclei, mitochondria, filaments), together with other structures derived from the virus infection. Among them, it was possible to detect viral factories and two types of viral particles related to different maturation steps of VACV (immature and mature particles), which were compared to images obtained by standard electron microscopy of the same type of cells. In addition, the effect of radiation damage during X-ray tomographic acquisition was analyzed. Thin sections studied by electron microscopy revealed that the morphological features of the cells do not present noticeable changes after irradiation. Our findings show that cryo X-ray nano-tomography is a powerful tool for collecting three-dimensional structural information from frozen, unfixed, unstained whole cells with sufficient resolution to detect different virus particles exhibiting distinct maturation levels. PMID:22178221

Chichón, Francisco Javier; Rodríguez, Maria Josefa; Pereiro, Eva; Chiappi, Michele; Perdiguero, Beatriz; Guttmann, Peter; Werner, Stephan; Rehbein, Stefan; Schneider, Gerd; Esteban, Mariano; Carrascosa, José L

2012-02-01

190

Cap-Independent Translation of mRNA Conferred by Encephalomyocarditis Virus 5' Sequence Improves the Performance of the Vaccinia Virus\\/Bacteriophage T7 Hybrid Expression System  

Microsoft Academic Search

A recombinant vaccinia virus that directs the synthesis of bacteriophage T7 RNA polymerase provides the basis for the expression of genes that are regulated by T7 promoters in mammalian cells. The T7 transcripts, which account for as much as 30% of the total cytoplasmic RNA at 24 hr after infection, are largely uncapped. To improve the translatability of the uncapped

Orna Elroy-Stein; Thomas R. Fuerst; Bernard Moss

1989-01-01

191

Nonsegmented Negative-Strand Viruses as Vaccine Vectors  

Microsoft Academic Search

The live-virus vector era began in 1983, when Smith, Mack- ett, and Moss constructed a recombinant vaccinia virus ex- pressing hepatitis B surface antigen and demonstrated the in- duction of hepatitis B-specific antibodies in rabbits immunized with the recombinant virus (113). Subsequently, live-virus vec- tors were developed with other DNA viruses, such as adeno- viruses and herpesviruses, and with positive-strand

Alexander Bukreyev; Mario H. Skiadopoulos; Brian R. Murphy; Peter L. Collins

2010-01-01

192

Studies on the synthesis of betahCG hormone in vero cells by recombinant vaccinia virus.  

PubMed

Synthesis of the beta-subunit of human chorionic gonado-tropin (betahCG) in Vero cells by the recombinant vaccinia virus has been studied. The yield of betahCG was a function of the multiplicity of infection (MOI), and was highest at 25 MOI. The kinetics of synthesis and initial secretion of betahCG, deduced from the pulse-chase experiments were "zero order." At 30 h postinfection, the relative values of net synthesis and secretion rates were 4.0 AU. mm(2) betahCG/10(6) cells. h and 1.55 AU. mm(2) betahCG/10(6) cells. h, respectively. The time required to secrete 50% of intracellular betahCG was 210 min. Pulse-chase data also showed that 24% of betahCG was degraded intracelluiarly within 10 h, of which 17% was detected in the autoradiogram. Along with 30 kD betahCG, a satellite band of 28 kD was evident among the peptide synthesized in Vero cells. The molecular weight of vaccinia-derived betahCG was 13 kD more that its nonglycosylated form, indicating extensive glycosylation in Vero cells. The mRNA levels in infected Vero cells at different postinfection times were quantified by excess DNA dot-blot hybridization. It appears that the Vero cell possesses some host cell-associated factor(s), which prevented the transcription of early betahCG-mRNA promoted by the early signal of the vaccinia P 7.5 promoter. The half-life of betahCG-mRNA, as determined by follow-up of decay after blocking transcription initiation, was found to be 6.4 h. The synthesized betahCG was immunoreactive as it reacted with monoclonal and polyclonal monospecific antibodies. The subunit was also biologically active, as it combined with native betahCG to form heterodimer betahCG, which competed with (125)I-hCG for radioreceptors and stimulated testosterone synthesis in Leydig cells. (c) 1995 John Wiley & Sons, Inc. PMID:18623472

Mukhopadhyay, A; Mukhopadhyay, S N; Talwar, G P

1995-10-20

193

Highly attenuated smallpox vaccine protects rabbits and mice against pathogenic orthopoxvirus challenge  

Microsoft Academic Search

The possible reemergence of smallpox through bioterrorism requires the preparation of adequate stockpiles of vaccine. Dryvax, the only US-licensed vaccinia virus smallpox vaccine, has an unacceptable safety profile in the pre-event setting. LC16m8 is a Japanese-licensed attenuated vaccinia virus strain that has been safely used in over 50,000 persons. Until now, efficacy of this vaccine was unproven. Using two animal

Cyril Empig; Julie R. Kenner; Marcel Perret-Gentil; Bryan E. Youree; Edward Bell; Allen Chen; Marc Gurwith; Keith Higgins; Michael Lock; Amanda D. Rice; Jill Schriewer; Faruk Sinangil; Elizabeth White; R. Mark Buller; Terence S. Dermody; Stuart N. Isaacs; Richard W. Moyer

2006-01-01

194

Novel vaccine strategies against emerging viruses  

PubMed Central

One of the main public health concerns of emerging viruses is their potential introduction into and sustained circulation among populations of immunologically naďve, susceptible hosts. The induction of protective immunity through vaccination can be a powerful tool to prevent this concern by conferring protection to the population at risk. Conventional approaches to develop vaccines against emerging pathogens have significant limitations: lack of experimental tools for several emerging viruses of concern, poor immunogenicity, safety issues, or lack of cross-protection against antigenic variants. The unpredictability of the emergence of future virus threats demands the capability to rapidly develop safe, effective vaccines. We describe some recent advances in new vaccine strategies that are being explored as alternatives to classical attenuated and inactivated vaccines, and provide examples of potential novel vaccines for emerging viruses. These approaches might be applied to the control of many other emerging pathogens. PMID:23477832

Garcia-Sastre, Adolfo; Mena, Ignacio

2013-01-01

195

Nucleotide sequence of 42 kbp of vaccinia virus strain WR from near the right inverted terminal repeat  

Microsoft Academic Search

The nucleotide sequence of 42 090 bp of vaccinia virus strain WR is presented. The sequence includes the SalI L, F, G and I fragments and starts near the centre of the HindIII A fragment and extends rightwards towards the genomic terminus, finishing approximately 0-5 kb internal of the inverted terminal repeat (ITR). Trans- lation of this region has identified

Geoffrey L. Smith; Y. Sang Chan; Susan T. Howard

1991-01-01

196

Extracts from rabbit skin inflamed by the vaccinia virus attenuate bupivacaine-induced spinal neurotoxicity in pregnant rats?  

PubMed Central

Extracts from rabbit skin inflamed by the vaccinia virus can relieve pain and promote repair of nerve injury. The present study intraperitoneally injected extracts from rabbit skin inflamed by the vaccinia virus for 3 and 4 days prior to and following intrathecal injection of bupivacaine into pregnant rats. The pain threshold test after bupivacaine injection showed that the maximum possible effect of tail-flick latency peaked 1 day after intrathecal injection of bupivacaine in the extract-pretreatment group, and gradually decreased, while the maximum possible effect in the bupivacaine group continued to increase after intrathecal injection of bupivacaine. Histological observation showed that after 4 days of intrathecal injection of bupivacaine, the number of shrunken, vacuolated, apoptotic and caspase-9-positive cells in the dorsal root ganglion in the extract-pretreatment group was significantly reduced compared with the bupivacaine group. These findings indicate that extracts from rabbit skin inflamed by the vaccinia virus can attenuate neurotoxicity induced by intrathecal injection of bupivacaine in pregnant rats, possibly by inhibiting caspase-9 protein expression and suppressing nerve cell apoptosis.

Cui, Rui; Xu, Shiyuan; Wang, Liang; Lei, Hongyi; Cai, Qingxiang; Zhang, Hongfei; Wang, Dongmei

2013-01-01

197

Development of heat-stable recombinant rinderpest vaccine  

Microsoft Academic Search

Summary Recombinant vaccinia virus (RVV) containing the full-length cDNA of rinderpest virus (RV)-haemagglutinin (H) gene was constructed. The H gene was inserted into the attenuated vaccine strain of vaccinia virus (VV), Lc 16 m0, with two different promoters, namely cowpox virus A-type inclusion body (ATI) promoter or VV 7.5 kilodalton (P7.5) promoter. These RVVs produced the same sized fully glycosylated

K. Tsukiyama; Y. Yoshikawa; H. Kamata; K. Imaoka; K. Asano; S. Funahashi; T. Maruyama; H. Shida; M. Sugimoto; K. Yamanouchi

1989-01-01

198

Modified vaccinia virus Ankara triggers type I IFN production in murine conventional dendritic cells via a cGAS/STING-mediated cytosolic DNA-sensing pathway.  

PubMed

Modified vaccinia virus Ankara (MVA) is an attenuated poxvirus that has been engineered as a vaccine against infectious agents and cancers. Our goal is to understand how MVA modulates innate immunity in dendritic cells (DCs), which can provide insights to vaccine design. In this study, using murine bone marrow-derived dendritic cells, we assessed type I interferon (IFN) gene induction and protein secretion in response to MVA infection. We report that MVA infection elicits the production of type I IFN in murine conventional dendritic cells (cDCs), but not in plasmacytoid dendritic cells (pDCs). Transcription factors IRF3 (IFN regulatory factor 3) and IRF7, and the positive feedback loop mediated by IFNAR1 (IFN alpha/beta receptor 1), are required for the induction. MVA induction of type I IFN is fully dependent on STING (stimulator of IFN genes) and the newly discovered cytosolic DNA sensor cGAS (cyclic guanosine monophosphate-adenosine monophosphate synthase). MVA infection of cDCs triggers phosphorylation of TBK1 (Tank-binding kinase 1) and IRF3, which is abolished in the absence of cGAS and STING. Furthermore, intravenous delivery of MVA induces type I IFN in wild-type mice, but not in mice lacking STING or IRF3. Treatment of cDCs with inhibitors of endosomal and lysosomal acidification or the lysosomal enzyme Cathepsin B attenuated MVA-induced type I IFN production, indicating that lysosomal enzymatic processing of virions is important for MVA sensing. Taken together, our results demonstrate a critical role of the cGAS/STING-mediated cytosolic DNA-sensing pathway for type I IFN induction in cDCs by MVA. We present evidence that vaccinia virulence factors E3 and N1 inhibit the activation of IRF3 and the induction of IFNB gene in MVA-infected cDCs. PMID:24743339

Dai, Peihong; Wang, Weiyi; Cao, Hua; Avogadri, Francesca; Dai, Lianpan; Drexler, Ingo; Joyce, Johanna A; Li, Xiao-Dong; Chen, Zhijian; Merghoub, Taha; Shuman, Stewart; Deng, Liang

2014-04-01

199

Cryo-X-ray tomography of vaccinia virus membranes and inner compartments.  

PubMed

Vitrified unstained purified vaccinia virus particles have been used as a test sample to evaluate the capabilities of cryo-X-ray tomography. Embedded in a thick layer of vitreous ice, the viral particles representing the mature form of the virus (MV) were visualized using full-field transmission X-ray tomography. The tomographic reconstructions reveal the viral brick-shaped characteristic structures with a size of 250x270x360nm(3). The X-ray tomograms show the presence of a clearly defined external envelope, together with an inner core surrounded by an internal envelope, including areas with clear differential density, which correlate well with those features previously described for these viral particles using electron microscopy analyses. A quantitative assessment of the resolution attained in X-ray and electron tomograms of the viral particles prepared under the same conditions yields values of 25.7 and 6.7nm half-pitch, respectively. Although the resolution of the X-ray microscope is well above the dimensions of the membranous compartments, the strong differential contrast exhibited makes it possible to precisely reveal them without any contrasting reagent within this small and complex biological sample. PMID:19616103

Carrascosa, José L; Chichón, Francisco Javier; Pereiro, Eva; Rodríguez, María Josefa; Fernández, Jose Jesús; Esteban, Mariano; Heim, Stefan; Guttmann, Peter; Schneider, Gerd

2009-11-01

200

Vaccinia virus virulence factor N1 can be ubiquitylated on multiple lysine residues  

PubMed Central

Ubiquitylation is a covalent post-translational modification that regulates protein stability and is involved in many biological functions. Proteins may be modified with mono-ubiquitin or ubiquitin chains. Viruses have evolved multiple mechanisms to perturb the cell ubiquitin system and manipulate it to their own benefit. Here, we report ubiquitylation of vaccinia virus (VACV) protein N1. N1 is an inhibitor of the nuclear factor NF-?B and apoptosis that contributes to virulence, has a Bcl-2-like fold, and is highly conserved amongst orthopoxviruses. The interaction between N1 and ubiquitin occurs at endogenous protein levels during VACV infection and following ectopic expression of N1. Biochemical analysis demonstrated that N1 is covalently ubiquitylated, and heterodimers of ubiquitylated and non-ubiquitylated N1 monomers were identified, suggesting that ubiquitylation does not inhibit N1 dimerization. Studies with other VACV Bcl-2 proteins, such as C6 or B14, revealed that although these proteins also interact with ubiquitin, these interactions are non-covalent. Finally, mutagenesis of N1 showed that ubiquitylation occurs in a conventional lysine-dependent manner at multiple acceptor sites because only an N1 allele devoid of lysine residues remained unmodified. Taken together, we described a previously uncharacterized modification of the VACV protein N1 that provided a new layer of complexity to the biology of this virulence factor, and provided another example of the intricate interplay between poxviruses and the host ubiquitin system. PMID:24914067

Maluquer de Motes, Carlos; Schiffner, Torben; Sumner, Rebecca P.

2014-01-01

201

Vaccinia virus l1 protein is required for cell entry and membrane fusion.  

PubMed

Genetic and biochemical studies have provided evidence for an entry/fusion complex (EFC) comprised of at least eight viral proteins (A16, A21, A28, G3, G9, H2, J5, and L5) that together with an associated protein (F9) participates in entry of vaccinia virus (VACV) into cells. The genes encoding these proteins are conserved in all poxviruses, are expressed late in infection, and are components of the mature virion membrane but are not required for viral morphogenesis. In addition, all but one component has intramolecular disulfides that are formed by the poxvirus cytoplasmic redox system. The L1 protein has each of the characteristics enumerated above except that it has been reported to be essential for virus assembly. To further investigate the role of L1, we constructed a recombinant VACV (vL1Ri) that inducibly expresses L1. In the absence of inducer, L1 synthesis was repressed and vL1Ri was unable to form plaques or produce infectious progeny. Unexpectedly, assembly and morphogenesis appeared normal and the noninfectious virus particles were indistinguishable from wild-type VACV as determined by transmission electron microscopy and analysis of the component polypeptides. Notably, the L1-deficient virions were able to attach to cells but the cores failed to penetrate into the cytoplasm. In addition, cells infected with vL1Ri in the absence of inducer did not form syncytia following brief low-pH treatment even though extracellular virus was produced. Coimmunoprecipitation experiments demonstrated that L1 interacted with the EFC and indirectly with F9, suggesting that L1 is an additional component of the viral entry apparatus. PMID:18596103

Bisht, Himani; Weisberg, Andrea S; Moss, Bernard

2008-09-01

202

The C11R gene, which encodes the vaccinia virus growth factor, is partially responsible for MVA-induced NF-?B and ERK2 activation.  

PubMed

MVA is an attenuated strain of vaccinia virus (VACV) that is a popular vaccine vector. MVA infection activates NF-?B. For 293T cells, it is known that MVA early gene expression activates extracellular signal-regulated kinase 2 (ERK2), resulting in NF-?B activation. However, other viral and cellular mechanisms responsible for this event are ill defined. The data presented here show that the epidermal growth factor receptor (EGFR) is at least one apical trigger in this pathway: ERK2 and NF-?B activation was diminished when MVA infections occurred in cells devoid of the EGFR (CHO K1 cells) or in the presence of a drug that inhibits EGFR activation (AG1478) in 293T cells. The expression of dominant negative Ras or Raf proteins still permitted NF-?B activation, suggesting that a nonclassical EGFR-based signal transduction pathway triggered ERK2-NF-?B activation. C11R is an early gene present in MVA and other orthopoxviruses. It encodes the soluble, secreted vaccinia virus growth factor (VGF), a protein that binds to and stimulates the EGFR. Here it was observed that NF-?B was activated in 293T cells transfected with a plasmid encoding the C11R gene. Silencing by small interfering RNA (siRNA) or deletion of the C11R gene (MVA?C11R) reduced both MVA-induced ERK2 and NF-?B activation in 293T cells or the keratinocyte line Hacat, suggesting that this mechanism of MVA-induced NF-?B activation may be common for several cell types. PMID:22740414

Martin, Stefani; Harris, Daniel T; Shisler, Joanna

2012-09-01

203

9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Bovine Virus Diarrhea Vaccine. 113.311 Section...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.311 Bovine...

2013-01-01

204

9 CFR 113.206 - Wart Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 false Wart Vaccine, Killed Virus. 113.206 Section 113.206 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart...

2010-01-01

205

9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.  

Code of Federal Regulations, 2013 CFR

... false Pseudorabies Vaccine, Killed Virus. 113.213 Section 113.213 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.213...

2013-01-01

206

9 CFR 113.206 - Wart Vaccine, Killed Virus.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 false Wart Vaccine, Killed Virus. 113.206 Section 113.206 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart...

2012-01-01

207

9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.  

... Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.210 Feline...

2014-01-01

208

9 CFR 113.206 - Wart Vaccine, Killed Virus.  

...2014-01-01 false Wart Vaccine, Killed Virus. 113.206 Section 113.206 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart...

2014-01-01

209

9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.  

... false Pseudorabies Vaccine, Killed Virus. 113.213 Section 113.213 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.213...

2014-01-01

210

9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 false Bovine Virus Diarrhea Vaccine. 113.311 Section...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.311 Bovine...

2012-01-01

211

9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.  

Code of Federal Regulations, 2012 CFR

... Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.210 Feline...

2012-01-01

212

9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.  

Code of Federal Regulations, 2011 CFR

...Avian Encephalomyelitis Vaccine, Killed Virus. 113.208 Section 113.208 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian...

2011-01-01

213

9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).  

... false Parvovirus Vaccine, Killed Virus (Canine). 113.214 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus...

2014-01-01

214

9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.  

Code of Federal Regulations, 2012 CFR

...Avian Encephalomyelitis Vaccine, Killed Virus. 113.208 Section 113.208 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian...

2012-01-01

215

9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).  

Code of Federal Regulations, 2011 CFR

... false Parvovirus Vaccine, Killed Virus (Canine). 113.214 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus...

2011-01-01

216

9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 2011-01-01 false Bovine Virus Diarrhea Vaccine. 113.311 Section...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.311 Bovine...

2011-01-01

217

9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.  

...2014-01-01 2014-01-01 false Bovine Virus Diarrhea Vaccine. 113.311 Section...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.311 Bovine...

2014-01-01

218

9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).  

Code of Federal Regulations, 2013 CFR

... false Parvovirus Vaccine, Killed Virus (Canine). 113.214 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus...

2013-01-01

219

9 CFR 113.206 - Wart Vaccine, Killed Virus.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 false Wart Vaccine, Killed Virus. 113.206 Section 113.206 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart...

2011-01-01

220

9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.  

Code of Federal Regulations, 2011 CFR

... Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.210 Feline...

2011-01-01

221

9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.  

...Avian Encephalomyelitis Vaccine, Killed Virus. 113.208 Section 113.208 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian...

2014-01-01

222

9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.  

Code of Federal Regulations, 2011 CFR

... false Pseudorabies Vaccine, Killed Virus. 113.213 Section 113.213 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.213...

2011-01-01

223

9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

...Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.211 Feline...

2010-01-01

224

9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.  

Code of Federal Regulations, 2013 CFR

...Avian Encephalomyelitis Vaccine, Killed Virus. 113.208 Section 113.208 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian...

2013-01-01

225

9 CFR 113.214 - Parvovirus Vaccine, Killed Virus (Canine).  

Code of Federal Regulations, 2012 CFR

... false Parvovirus Vaccine, Killed Virus (Canine). 113.214 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.214 Parvovirus...

2012-01-01

226

9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.  

Code of Federal Regulations, 2012 CFR

...Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.211 Feline...

2012-01-01

227

9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

... Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.210 Feline...

2010-01-01

228

9 CFR 113.210 - Feline Calicivirus Vaccine, Killed Virus.  

Code of Federal Regulations, 2013 CFR

... Feline Calicivirus Vaccine, Killed Virus. 113.210 Section 113.210 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.210 Feline...

2013-01-01

229

9 CFR 113.208 - Avian Encephalomyelitis Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

...Avian Encephalomyelitis Vaccine, Killed Virus. 113.208 Section 113.208 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.208 Avian...

2010-01-01

230

9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.  

Code of Federal Regulations, 2011 CFR

...Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.211 Feline...

2011-01-01

231

9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.  

Code of Federal Regulations, 2013 CFR

...Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.211 Feline...

2013-01-01

232

9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.  

Code of Federal Regulations, 2012 CFR

... false Pseudorabies Vaccine, Killed Virus. 113.213 Section 113.213 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.213...

2012-01-01

233

9 CFR 113.206 - Wart Vaccine, Killed Virus.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 false Wart Vaccine, Killed Virus. 113.206 Section 113.206 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.206 Wart...

2013-01-01

234

9 CFR 113.311 - Bovine Virus Diarrhea Vaccine.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Bovine Virus Diarrhea Vaccine. 113.311 Section...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.311 Bovine...

2010-01-01

235

9 CFR 113.211 - Feline Rhinotracheitis Vaccine, Killed Virus.  

...Feline Rhinotracheitis Vaccine, Killed Virus. 113.211 Section 113.211 Animals...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.211 Feline...

2014-01-01

236

Products and substrate/template usage of vaccinia virus DNA primase  

SciTech Connect

Vaccinia virus encodes a 90-kDa protein conserved in all poxviruses, with DNA primase and nucleoside triphosphatase activities. DNA primase products, synthesized with a single stranded {phi}X174 DNA template, were resolved as dinucleotides and long RNAs on denaturing polyacrylamide and agarose gels. Following phosphatase treatment, the dinucleotides GpC and ApC in a 4:1 ratio were identified by nearest neighbor analysis in which {sup 32}P was transferred from [{alpha}-{sup 32}P]CTP to initiating purine nucleotides. Differences in the nucleotide binding sites for initiation and elongation were suggested by the absence of CpC and UpC dinucleotides as well as the inability of deoxynucleotides to mediate primer synthesis despite their incorporation into mixed RNA/DNA primers. Strong primase activity was detected with an oligo(dC) template. However, there was only weak activity with an oligo(dT) template and none with oligo(dA) or oligo(dG). The absence of stringent template specificity is consistent with a role for the enzyme in priming DNA synthesis at the replication fork.

De Silva, Frank S.; Paran, Nir [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0445 (United States); Moss, Bernard [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0445 (United States)], E-mail: bmoss@nih.gov

2009-01-05

237

Study of Vaccinia and Cowpox viruses' replication in Rac1-N17 dominant-negative cells  

PubMed Central

Interfering with cellular signal transduction pathways is a common strategy used by many viruses to create a propitious intracellular environment for an efficient replication. Our group has been studying cellular signalling pathways activated by the orthopoxviruses Vaccinia (VACV) and Cowpox (CPXV) and their significance to viral replication. In the present study our aim was to investigate whether the GTPase Rac1 was an upstream signal that led to the activation of MEK/ERK1/2, JNK1/2 or Akt pathways upon VACV or CPXV' infections. Therefore, we generated stable murine fibroblasts exhibiting negative dominance to Rac1-N17 to evaluate viral growth and the phosphorylation status of ERK1/2, JNK1/2 and Akt. Our results demonstrated that VACV replication, but not CPXV, was affected in dominant-negative (DN) Rac1-N17 cell lines in which viral yield was reduced in about 10-fold. Viral late gene expression, but not early, was also reduced. Furthermore, our data showed that Akt phosphorylation was diminished upon VACV infection in DN Rac1-N17 cells, suggesting that Rac1 participates in the phosphoinositide-3 kinase pathway leading to the activation of Akt. In conclusion, our results indicate that while Rac1 indeed plays a role in VACV biology, perhaps another GTPase may be involved in CPXV replication. PMID:23903969

Salgado, Ana Paula Carneiro; Soares-Martins, Jamaria Adriana Pinheiro; Andrade, Luciana Garcia; Albarnaz, Jonas Dutra; Ferreira, Paulo Cesar Peregrino; Kroon, Erna Geessien; Bonjardim, Claudio Antonio

2013-01-01

238

Mechanism of Antiviral Drug Resistance of Vaccinia Virus: Identification of Residues in the Viral DNA Polymerase Conferring Differential Resistance to Antipoxvirus Drugs  

Microsoft Academic Search

The acyclic nucleoside phosphonate (ANP) family of drugs shows promise as therapeutics for treating poxvirus infections. However, it has been questioned whether the utility of these compounds could be com- promised through the intentional genetic modification of viral sequences by bioterrorists or the selection of drug resistance viruses during the course of antiviral therapy. To address these concerns, vaccinia virus

Don B. Gammon; Robert Snoeck; Pierre Fiten; M. Krecmerova; Antonín Holy ´; E. De Clercq; G. Opdenakker; D. H. Evans; G. Andrei

2008-01-01

239

Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B'\\/C Candidate Vaccine  

Microsoft Academic Search

Background: We conducted a Phase I dose-escalation trial of ADMVA, a Clade-B'\\/C-based HIV-1 candidate vaccine expressing env, gag, pol, nef, and tat in a modified vaccinia Ankara viral vector. Sequences were derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in

Sandhya Vasan; Sarah J. Schlesinger; Zhiwei Chen; Arlene Hurley; Angela Lombardo; Soe Than; Phumla Adesanya; Catherine Bunce; Mark Boaz; Rosanne Boyle; Eddy Sayeed; Lorna Clark; Daniel Dugin; Mar Boente-Carrera; Claudia Schmidt; Qing Fang; Lei; Yaoxing Huang; Gerasimos J. Zaharatos; David F. Gardiner; Marina Caskey; Laura Seamons; Martin Ho; Len Dally; Carol Smith; Josephine Cox; Dilbinder Gill; Jill Gilmour; Michael C. Keefer; Patricia Fast; David D. Ho

2010-01-01

240

Phase 1 Safety and Immunogenicity Evaluation of ADMVA, a Multigenic, Modified Vaccinia Ankara-HIV-1 B'\\/C Candidate Vaccine  

Microsoft Academic Search

BackgroundWe conducted a Phase I dose-escalation trial of ADMVA, a Clade-B'\\/C-based HIV-1 candidate vaccine expressing env, gag, pol, nef, and tat in a modified vaccinia Ankara viral vector. Sequences were derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in human

Sandhya Vasan; Sarah J. Schlesinger; Zhiwei Chen; Arlene Hurley; Angela Lombardo; Soe Than; Phumla Adesanya; Catherine Bunce; Mark Boaz; Rosanne Boyle; Eddy Sayeed; Lorna Clark; Daniel Dugin; Mar Boente-Carrera; Claudia Schmidt; Qing Fang; Ba Lei; Yaoxing Huang; Gerasimos J. Zaharatos; David F. Gardiner; Marina Caskey; Laura Seamons; Martin Ho; Len Dally; Carol Smith; Josephine Cox; Dilbinder Gill; Jill Gilmour; Michael C. Keefer; Patricia Fast; David D. Ho; Sean Emery

2010-01-01

241

Structural Determinants of Caspase-9 Inhibition by the Vaccinia Virus Protein, F1L*  

PubMed Central

In multicellular organisms, apoptosis is a powerful method of host defense against viral infection. Apoptosis is mediated by a cascade of caspase-family proteases that commit infected cells to a form of programmed cell death. Therefore, to replicate within host cells, viruses have developed various strategies to inhibit caspase activation. In the mitochondrial cell-death pathway, release of cytochrome c from mitochondria into the cytosol triggers assembly of the oligomeric apoptosome, resulting in dimerization and activation of the apical caspase-9 (C9), and in turn its downstream effector caspases, leading to apoptosis. We previously showed that the vaccinia virus-encoded Bcl-2-like protein, F1L, which suppresses cytochrome c release by binding Bcl-2 family proteins, is also a C9 inhibitor. Here, we identify a novel motif within the flexible N-terminal region of F1L that is necessary and sufficient for interaction with and inhibition of C9. Based on functional studies and mutagenesis, we developed an atomic model of the complex in which F1L inhibits C9 by engaging the active site in the reverse orientation with respect to substrate peptides, in a manner analogous to that of XIAP-mediated inhibition of caspases-3 and -7. These studies offer new insights into the mechanism of apoptosome inhibition by F1L as well as novel probes to understand the molecular bases of apoptosome regulation and turnover. They also suggest how the two distinct functionalities of F1L (inhibition of C9 and suppression of pro-apoptotic Bcl-2 family proteins) may operate in a cellular setting. PMID:21757755

Yu, Eric; Zhai, Dayong; Jin, Chaofang; Gerlic, Motti; Reed, John C.; Liddington, Robert

2011-01-01

242

Primary Human Leukocyte Subsets Differentially Express Vaccinia Virus Receptors Enriched in Lipid Rafts  

PubMed Central

Poxviruses, including vaccinia virus (VV) and canarypox virus (ALVAC), do not indiscriminately infect all cell types of the primary human leukocytes (PHLs) that they encounter but instead demonstrate an extremely strong bias toward infection of monocytes and monocyte lineage cells. We studied the specific molecular events that determine the VV tropism for major PHL subsets including monocytes, B cells, neutrophils, NK cells, and T cells. We found that VV exhibited an extremely strong bias of cell surface protein-dependent binding to monocytes, B cells, and activated T cells to a similar degree and to neutrophils to a much lesser extent. Resting T cells and resting NK cells exhibited only trace amounts of VV binding. Activated T cells, however, became permissive to VV binding, infection, and replication, while activated NK cells still resisted VV binding. VV binding strongly colocalized with lipid rafts on the surfaces of all VV binding-susceptible PHL subsets, even when lipid rafts were relocated to cell uropods upon cell polarization. Immunosera raised against detergent-resistant membranes (DRMs) from monocytes or activated T cells, but not resting T cells, effectively cross-blocked VV binding to and infection of PHL subsets. CD29 and CD98, two lipid raft-associated membrane proteins that had been found to be important for VV entry into HeLa cells, had no effect on VV binding to and infection of primary activated T cells. Our data indicate that PHL subsets express VV protein receptors enriched in lipid rafts and that receptors are cross-presented on all susceptible PHLs. PMID:23785200

Byrd, Daniel; Amet, Tohti; Hu, Ningjie; Lan, Jie; Hu, Sishun

2013-01-01

243

Vaccinia Virus Morphogenesis: A13 Phosphoprotein Is Required for Assembly of Mature Virions  

PubMed Central

The 70-amino-acid A13L protein is a component of the vaccinia virus membrane. We demonstrate here that the protein is expressed at late times of infection, undergoes phosphorylation at a serine residue(s), and becomes encapsidated in a monomeric form. Phosphorylation is dependent on Ser40, which lies within the proline-rich motif SPPP. Because phosphorylation of the A13 protein is only minimally affected by disruption of the viral F10 kinase or H1 phosphatase, a cellular kinase is likely to be involved. We generated an inducible recombinant in which A13 protein expression is dependent upon the inclusion of tetracycline in the culture medium. Repression of the A13L protein spares the biochemical progression of the viral life cycle but arrests virion morphogenesis. Virion assembly progresses through the formation of immature virions (IVs); however, these virions do not acquire nucleoids, and DNA crystalloids accumulate in the cytoplasm. Further development into intracellular mature virions is blocked, causing a 1,000-fold decrease in the infectious virus yield relative to that obtained in the presence of the inducer. We also determined that the temperature-sensitive phenotype of the viral mutant Cts40 is due to a nucleotide transition within the A13L gene that causes a Thr48?Ile substitution. This substitution disrupts the function of the A13 protein but does not cause thermolability of the protein; at the nonpermissive temperature, virion morphogenesis arrests at the stage of IV formation. The A13L protein, therefore, is part of a newly recognized group of membrane proteins that are dispensable for the early biogenesis of the virion membrane but are essential for virion maturation. PMID:15280497

Unger, Bethany; Traktman, Paula

2004-01-01

244

Attacking Postoperative Metastases using Perioperative Oncolytic Viruses and Viral Vaccines  

PubMed Central

Surgical resection of solid primary malignancies is a mainstay of therapy for cancer patients. Despite being the most effective treatment for these tumors, cancer surgery has been associated with impaired metastatic clearance due to immunosuppression. In preclinical surgery models and human cancer patients, we and others have demonstrated a profound suppression of both natural killer (NK) and T cell function in the postoperative period and this plays a major role in the enhanced development of metastases following surgery. Oncolytic viruses (OV) were originally designed to selectively infect and replicate in tumors, with the primary objective of directly lysing cancer cells. It is becoming increasingly clear, however, that OV infection results in a profound inflammatory reaction within the tumor, initiating innate and adaptive immune responses against it that is critical for its therapeutic benefit. This anti-tumor immunity appears to be mediated predominantly by NK and cytotoxic T cells. In preclinical models, we found that preoperative OV prevents postoperative NK cell dysfunction and attenuates tumor dissemination. Due to theoretical safety concerns of administering live virus prior to surgery in cancer patients, we characterized safe, attenuated versions of OV, and viral vaccines that could stimulate NK cells and reduce metastases when administered in the perioperative period. In cancer patients, we observed that in vivo infusion with oncolytic vaccinia virus and ex vivo stimulation with viral vaccines promote NK cell activation. These preclinical studies provide a novel and clinically relevant setting for OV therapy. Our challenge is to identify safe and promising OV therapies that will activate NK and T cells in the perioperative period preventing the establishment of micrometastatic disease in cancer patients. PMID:25161958

Tai, Lee-Hwa; Auer, Rebecca

2014-01-01

245

Protective Effect of Surfactant Protein D in Pulmonary Vaccinia Virus Infection: Implication of A27 Viral Protein  

PubMed Central

Vaccinia virus (VACV) was used as a surrogate of variola virus (VARV) (genus Orthopoxvirus), the causative agent of smallpox, to study Orthopoxvirus infection. VARV is principally transmitted between humans by aerosol droplets. Once inhaled, VARV first infects the respiratory tract where it could encounter surfactant components, such as soluble pattern recognition receptors. Surfactant protein D (SP-D), constitutively present in the lining fluids of the respiratory tract, plays important roles in innate host defense against virus infection. We investigated the role of SP-D in VACV infection and studied the A27 viral protein involvement in the interaction with SP-D. Interaction between SP-D and VACV caused viral inhibition in a lung cell model. Interaction of SP-D with VACV was mediated by the A27 viral protein. Binding required Ca2+ and interactions were blocked in the presence of excess of SP-D saccharide ligands. A27, which lacks glycosylation, directly interacted with SP-D. The interaction between SP-D and the viral particle was also observed using electron microscopy. Infection of mice lacking SP-D (SP-D-/-) resulted in increased mortality compared to SP-D+/+ mice. Altogether, our data show that SP-D participates in host defense against the vaccinia virus infection and that the interaction occurs with the viral surface protein A27. PMID:23518578

Julien, Perino; Thielens, Nicole M.; Crouch, Erika; Spehner, Daniele; Crance, Jean-Marc; Favier, Anne-Laure

2013-01-01

246

Vaccines in development against West Nile virus.  

PubMed

West Nile encephalitis emerged in 1999 in the United States, then rapidly spread through the North American continent causing severe disease in human and horses. Since then, outbreaks appeared in Europe, and in 2012, the United States experienced a new severe outbreak reporting a total of 5,387 cases of West Nile virus (WNV) disease in humans, including 243 deaths. So far, no human vaccine is available to control new WNV outbreaks and to avoid worldwide spreading. In this review, we discuss the state-of-the-art of West Nile vaccine development and the potential of a novel safe and effective approach based on recombinant live attenuated measles virus (MV) vaccine. MV vaccine is a live attenuated negative-stranded RNA virus proven as one of the safest, most stable and effective human vaccines. We previously described a vector derived from the Schwarz MV vaccine strain that stably expresses antigens from emerging arboviruses, such as dengue, West Nile or chikungunya viruses, and is strongly immunogenic in animal models, even in the presence of MV pre-existing immunity. A single administration of a recombinant MV vaccine expressing the secreted form of WNV envelope glycoprotein elicited protective immunity in mice and non-human primates as early as two weeks after immunization, indicating its potential as a human vaccine. PMID:24084235

Brandler, Samantha; Tangy, Frederic

2013-10-01

247

Immunization with influenza A NP-expressing vaccinia virus recombinant protects mice against experimental infection with human and avian influenza viruses  

Microsoft Academic Search

Summary.  Two-fold immunization of Balb\\/c mice with a vaccinia virus recombinant expressing the NP protein of influenza A\\/PR8\\/34 (H1N1)\\u000a virus under the control of a strong synthetic promoter induced specific antibodies and protected animals against low-dose\\u000a challenge by mouse-adapted heterosubtypic variants of human A\\/Aichi2\\/68 (H3N2) and avian A\\/Mallard\\/Pennsylvania\\/10218\\/84 (H5N2)\\u000a influenza virus strains. The surviving immunized animals had lower anti-hemagglutinin antibody titers

A. D. Altstein; A. K. Gitelman; Y. A. Smirnov; L. M. Piskareva; L. G. Zakharova; G. V. Pashvykina; M. M. Shmarov; O. P. Zhirnov; N. P. Varich; P. O. Ilyinskii; A. M. Shneider

2006-01-01

248

ORIGINAL ARTICLE CD40 ligand and tdTomato-armed vaccinia virus for induction  

E-print Network

effective expression of functional CD40L both in vitro and in vivo. In a xenograft model of bladder within an infected host. In the current work, we have used a Western Reserve double-deleted vaccinia

Hemminki, Akseli

249

GMCSF-armed vaccinia virus induces an antitumor immune Suvi Parviainen1  

E-print Network

growth factor (VGF) genes.5�7 These genes are necessary for replication in normal cells but not in cancer: thymidine kinase; VGF: vaccinia growth factor Additional Supporting Information may be found in the online

Hemminki, Akseli

250

Virotherapy of Canine Tumors with Oncolytic Vaccinia Virus GLV-1h109 Expressing an Anti-VEGF Single-Chain Antibody  

PubMed Central

Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor) single-chain antibody (scAb) GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 and the oncolytic and immunological effects of the GLV-1h109 vaccinia virus strain against canine soft tissue sarcoma and canine prostate carcinoma in xenograft models. Cell culture data demonstrated that the GLV-1h109 virus efficiently infect, replicate in and destroy both tested canine cancer cell lines. In addition, successful expression of GLAF-1 was demonstrated in virus-infected canine cancer cells and the antibody specifically recognized canine VEGF. In two different xenograft models, the systemic administration of the GLV-1h109 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice. Furthermore, tumor-specific virus infection led to a continued production of functional scAb GLAF-1, resulting in inhibition of angiogenesis. Overall, the GLV-1h109-mediated cancer therapy and production of immunotherapeutic anti-VEGF scAb may open the way for combination therapy concept i.e. vaccinia virus mediated oncolysis and intratumoral production of therapeutic drugs in canine cancer patients. PMID:23091626

Adelfinger, Marion; Donat, Ulrike; Hess, Michael; Weibel, Stephanie; Nolte, Ingo; Frentzen, Alexa; Szalay, Aladar A.

2012-01-01

251

Virotherapy of canine tumors with oncolytic vaccinia virus GLV-1h109 expressing an anti-VEGF single-chain antibody.  

PubMed

Virotherapy using oncolytic vaccinia virus (VACV) strains is one promising new strategy for cancer therapy. We have previously reported that oncolytic vaccinia virus strains expressing an anti-VEGF (Vascular Endothelial Growth Factor) single-chain antibody (scAb) GLAF-1 exhibited significant therapeutic efficacy for treatment of human tumor xenografts. Here, we describe the use of oncolytic vaccinia virus GLV-1h109 encoding GLAF-1 for canine cancer therapy. In this study we analyzed the virus-mediated delivery and production of scAb GLAF-1 and the oncolytic and immunological effects of the GLV-1h109 vaccinia virus strain against canine soft tissue sarcoma and canine prostate carcinoma in xenograft models. Cell culture data demonstrated that the GLV-1h109 virus efficiently infect, replicate in and destroy both tested canine cancer cell lines. In addition, successful expression of GLAF-1 was demonstrated in virus-infected canine cancer cells and the antibody specifically recognized canine VEGF. In two different xenograft models, the systemic administration of the GLV-1h109 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice. Furthermore, tumor-specific virus infection led to a continued production of functional scAb GLAF-1, resulting in inhibition of angiogenesis. Overall, the GLV-1h109-mediated cancer therapy and production of immunotherapeutic anti-VEGF scAb may open the way for combination therapy concept i.e. vaccinia virus mediated oncolysis and intratumoral production of therapeutic drugs in canine cancer patients. PMID:23091626

Patil, Sandeep S; Gentschev, Ivaylo; Adelfinger, Marion; Donat, Ulrike; Hess, Michael; Weibel, Stephanie; Nolte, Ingo; Frentzen, Alexa; Szalay, Aladar A

2012-01-01

252

Formation and intracellular localization of hepatitis C virus envelope glycoprotein complexes expressed by recombinant vaccinia and Sindbis viruses.  

PubMed Central

Hepatitis C virus (HCV) encodes two putative virion glycoproteins (E1 and E2) which are released from the polyprotein by signal peptidase cleavage. In this report, we have characterized the complexes formed between E1 and E2 (called E1E2) for two different HCV strains (H and BK) and studied their intracellular localization. Vaccinia virus and Sindbis virus vectors were used to express the HCV structural proteins in three different cell lines (HepG2, BHK-21, and PK-15). The kinetics of association between E1 and E2, as studied by pulse-chase analysis and coprecipitation of E2 with an anti-E1 monoclonal antibody, indicated that formation of stable E1E2 complexes is slow. The times required for half-maximal association between E1 and E2 were 60 to 85 min for the H strain and more than 165 min for the BK strain. In the presence of nonionic detergents, two forms of E1E2 complexes were detected. The predominant form was a heterodimer of E1 and E2 stabilized by noncovalent interactions. A minor fraction consisted of heterogeneous disulfide-linked aggregates, which most likely represent misfolded complexes. Posttranslational processing and localization of the HCV glycoproteins were examined by acquisition of endoglycosidase H resistance, subcellular fractionation, immunofluorescence, cell surface immunostaining, and immunoelectron microscopy. HCV glycoproteins containing complex N-linked glycans were not observed, and the proteins were not detected at the cell surface. Rather, the proteins localized predominantly to the endoplasmic reticular network, suggesting that some mechanism exists for their retention in this compartment. Images PMID:8083956

Dubuisson, J; Hsu, H H; Cheung, R C; Greenberg, H B; Russell, D G; Rice, C M

1994-01-01

253

Gold nanorod vaccine for respiratory syncytial virus  

PubMed Central

Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, confocal microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine-induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response. PMID:23799651

Stone, John W.; Thornburg, Natalie J.; Blum, David L.; Kuhn, Sam J.; Wright, David W.; Crowe, James E.

2013-01-01

254

Gold nanorod vaccine for respiratory syncytial virus  

NASA Astrophysics Data System (ADS)

Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, electron microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response.

Stone, John W.; Thornburg, Natalie J.; Blum, David L.; Kuhn, Sam J.; Wright, David W.; Crowe, James E., Jr.

2013-07-01

255

Emerging Respiratory Viruses: Challenges and Vaccine Strategies  

PubMed Central

The current threat of avian influenza to the human population, the potential for the reemergence of severe acute respiratory syndrome (SARS)-associated coronavirus, and the identification of multiple novel respiratory viruses underline the necessity for the development of therapeutic and preventive strategies to combat viral infection. Vaccine development is a key component in the prevention of widespread viral infection and in the reduction of morbidity and mortality associated with many viral infections. In this review we describe the different approaches currently being evaluated in the development of vaccines against SARS-associated coronavirus and avian influenza viruses and also highlight the many obstacles encountered in the development of these vaccines. Lessons learned from current vaccine studies, coupled with our increasing knowledge of the host and viral factors involved in viral pathogenesis, will help to increase the speed with which efficacious vaccines targeting newly emerging viral pathogens can be developed. PMID:17041137

Gillim-Ross, Laura; Subbarao, Kanta

2006-01-01

256

West Nile virus seroconversion in penguins after vaccination with a killed virus vaccine or a DNA vaccine.  

PubMed

To investigate the serologic response of penguins to West Nile virus (WNV) vaccines, four species of exclusively indoor-housed penguins, negative for WNV by serology, were evaluated: Humboldt (Spheniscus humboldti), Magellanic (Spheniscus magellanicus), Gentoo (Pygoscelis papua), and Rockhopper (Eudyptes chrysoscome) penguins. Birds were inoculated with either a killed virus vaccine or a plasmid-mediated DNA WNV vaccine, and postinoculation serology was evaluated. Both vaccines induced seroconversion in all four species, and no adverse reactions were noted. Postvaccination serology results varied across species and vaccine types. However, in all four species, the killed virus vaccine resulted in a greater seroconversion rate than the DNA vaccine and in a significantly shorter time period. Additionally, the duration of the seropositive titer was significantly longer in those birds vaccinated with the killed virus vaccine compared with those vaccinated with the DNA vaccine. A subset of unvaccinated penguins serving as negative controls remained negative throughout the duration of the study despite the presence of WNV in the geographic locations of the study, suggesting that indoor housing may minimize exposure to the virus and may be an additional means of preventing WNV infection in penguins. PMID:19110700

Davis, Michelle R; Langan, Jennifer N; Johnson, Yvette J; Ritchie, Branson W; Van Bonn, William

2008-12-01

257

Loss of Protein Kinase PKR Expression in Human HeLa Cells Complements the Vaccinia Virus E3L Deletion Mutant Phenotype by Restoration of Viral Protein Synthesis  

Microsoft Academic Search

The E3L proteins encoded by vaccinia virus bind double-stranded RNA and mediate interferon resistance, promote virus growth, and impair virus-mediated apoptosis. Among the cellular proteins implicated as targets of E3L is the protein kinase regulated by RNA (PKR). To test in human cells the role of PKR in conferring the E3L mutant phenotype, HeLa cells stably deficient in PKR generated

Ping Zhang; Bertram L. Jacobs; Charles E. Samuel

2008-01-01

258

De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection  

PubMed Central

The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and ?-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial ?-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their ?-oxidation drives robust ATP production. PMID:24651651

Greseth, Matthew D.; Traktman, Paula

2014-01-01

259

Altered CD8+ T cell immunodominance after vaccinia virus infection and the na?ve repertoire in inbred and F1 mice1  

PubMed Central

Previous studies of CD8+ T cell immunodominance after primary virus infection of F1 mice compared with their inbred parents have generally concluded that no dramatic changes occur. Here we re-visit this issue using vaccinia virus (VACV), which has a large genome, a recently defined immunodominance hierarchy in mice and is a candidate vector for vaccines. We found that immunogenicity of VACV peptides defined using inbred mice was highly variable in F1 progeny: some peptides were equally immunogenic in F1 and inbred, while others elicited responses that were reduced by more than 90% in F1 mice. Further, the dominance of a peptide in the relevant inbred parent did not predict whether or not it would be poorly immunogenic in F1 mice. This result held using F1 hybrids of MHC-congenic mice, suggesting that MHC differences alone were responsible. It was also extended to foreign epitopes expressed by a recombinant VACV vaccine. F1 mice were less able to mount responses to the poorly immunogenic peptides when used as a sole immunogen, ruling out immunodomination. In addition, conserved TCR V? usage between inbred and F1 mice did not always correlate with strong responses in F1 mice. However direct estimation of naďve precursor numbers showed that these were reduced in F1 compared with inbred mice for specificities that were poorly immunogenic in the hybrids. These data have implications for our understanding of the extent to which MHC diversity alters the range of epitopes that are immunogenic in outbred populations. PMID:19949110

Flesch, Inge E.A.; Woo, Wai-Ping; Wang, Yang; Panchanathan, Vijay; Wong, Yik-Chun; La Gruta, Nicole L.; Cukalac, Tania; Tscharke, David C.

2010-01-01

260

Mutations conferring resistance to viral DNA polymerase inhibitors in camelpox virus give different drug-susceptibility profiles in vaccinia virus.  

PubMed

Cidofovir or (S)-HPMPC is one of the three antiviral drugs that might be used for the treatment of orthopoxvirus infections. (S)-HPMPC and its 2,6-diaminopurine counterpart, (S)-HPMPDAP, have been described to select, in vitro, for drug resistance mutations in the viral DNA polymerase (E9L) gene of vaccinia virus (VACV). Here, to extend our knowledge of drug resistance development among orthopoxviruses, we selected, in vitro, camelpox viruses (CMLV) resistant to (S)-HPMPDAP and identified a single amino acid change, T831I, and a double mutation, A314V+A684V, within E9L. The production of recombinant CMLV and VACV carrying these amino acid substitutions (T831I, A314V, or A314V+A684V) demonstrated clearly their involvement in conferring reduced sensitivity to viral DNA polymerase inhibitors, including (S)-HPMPDAP. Both CMLV and VACV harboring the A314V change showed comparable drug-susceptibility profiles to various antivirals and similar impairments in viral growth. In contrast, the single change T831I and the double change A314V+A684V in VACV were responsible for increased levels of drug resistance and for cross-resistance to viral DNA polymerase antivirals that were not observed with their CMLV counterparts. Each amino acid change accounted for an attenuated phenotype of VACV in vivo. Modeling of E9L suggested that the T?I change at position 831 might abolish hydrogen bonds between E9L and the DNA backbone and have a direct impact on the incorporation of the acyclic nucleoside phosphonates. Our findings demonstrate that drug-resistance development in two related orthopoxvirus species may impact drug-susceptibility profiles and viral fitness differently. PMID:22532673

Duraffour, Sophie; Andrei, Graciela; Topalis, Dimitri; Kre?merová, Marcela; Crance, Jean-Marc; Garin, Daniel; Snoeck, Robert

2012-07-01

261

Mutations Conferring Resistance to Viral DNA Polymerase Inhibitors in Camelpox Virus Give Different Drug-Susceptibility Profiles in Vaccinia Virus  

PubMed Central

Cidofovir or (S)-HPMPC is one of the three antiviral drugs that might be used for the treatment of orthopoxvirus infections. (S)-HPMPC and its 2,6-diaminopurine counterpart, (S)-HPMPDAP, have been described to select, in vitro, for drug resistance mutations in the viral DNA polymerase (E9L) gene of vaccinia virus (VACV). Here, to extend our knowledge of drug resistance development among orthopoxviruses, we selected, in vitro, camelpox viruses (CMLV) resistant to (S)-HPMPDAP and identified a single amino acid change, T831I, and a double mutation, A314V+A684V, within E9L. The production of recombinant CMLV and VACV carrying these amino acid substitutions (T831I, A314V, or A314V+A684V) demonstrated clearly their involvement in conferring reduced sensitivity to viral DNA polymerase inhibitors, including (S)-HPMPDAP. Both CMLV and VACV harboring the A314V change showed comparable drug-susceptibility profiles to various antivirals and similar impairments in viral growth. In contrast, the single change T831I and the double change A314V+A684V in VACV were responsible for increased levels of drug resistance and for cross-resistance to viral DNA polymerase antivirals that were not observed with their CMLV counterparts. Each amino acid change accounted for an attenuated phenotype of VACV in vivo. Modeling of E9L suggested that the T?I change at position 831 might abolish hydrogen bonds between E9L and the DNA backbone and have a direct impact on the incorporation of the acyclic nucleoside phosphonates. Our findings demonstrate that drug-resistance development in two related orthopoxvirus species may impact drug-susceptibility profiles and viral fitness differently. PMID:22532673

Andrei, Graciela; Topalis, Dimitri; Krecmerova, Marcela; Crance, Jean-Marc; Garin, Daniel; Snoeck, Robert

2012-01-01

262

Mutations in the E9L Polymerase Gene of Cidofovir-Resistant Vaccinia Virus Strain WR Are Associated with the Drug Resistance Phenotype?  

PubMed Central

Cidofovir (CDV) is an effective drug against viruses of the Orthopoxviridae family and is active in vitro against variola virus, the cause of smallpox. However, CDV-resistant poxviruses can be generated by repeated in vitro passage in the presence of suboptimal concentrations of CDV. To determine if mutations in the E9L polymerase gene could confer resistance to this nucleoside analog, this gene was sequenced from CDV-resistant vaccinia virus and found to encode five amino acid changes, centered on an N-terminal region associated with 3??5? exonuclease activity. Transfer of this mutant E9L gene into wild-type vaccinia virus by marker rescue sufficed to confer the resistance phenotype. E9L polymerase mutations occurred sequentially during passage in CDV, and an H296Y/S338F double mutant that conferred an intermediate CDV resistance phenotype was identified. In vitro, the marker-rescued CDV-resistant vaccinia virus containing all five mutations grew nearly as well as wild-type vaccinia virus. However, the virulence of this virus for mice was reduced, as 10- to 30-fold more CDV-resistant virus than wild-type virus was required for lethality following intranasal challenge. Cidofovir and hexadecyloxypropyl-cidofovir gave partial protection to mice infected with the virus when used at 50 and 100 mg/kg of body weight given as single treatments 24 h after virus exposure, whereas 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (compound S2242) was completely protective at 25, 50, and 100 mg/kg/day when given daily for 5 days. These findings suggest that drug therapy for poxviruses may be complicated by drug resistance but that treatment of the infection with currently known compounds is possible. PMID:16982794

Kornbluth, Richard S.; Smee, Donald F.; Sidwell, Robert W.; Snarsky, Victoria; Evans, David H.; Hostetler, Karl Y.

2006-01-01

263

SMAC-armed vaccinia virus induces both apoptosis and necroptosis and synergizes the efficiency of vinblastine in HCC.  

PubMed

Hepatocellular carcinoma (HCC) has particularly high incidence rate in Asia and its resistance to the chemotherapeutic drugs and cell death make it intractable. Vaccinia virus (VV) is a potential vehicle and has been widely used in cancer therapy. SMAC/DIABLO is a critical factor in activating caspases and eliminating inhibition of IAPs when the programmed cell death is promoted. In this study, we constructed a tumor-targeted vaccinia virus carrying SMAC/DIABLO gene that was knocked in the region of viral thymidine kinase gene (VV-SMAC). Our results showed that VV-SMAC efficiently infected and destroyed HCC cells via triggering both caspase-dependent apoptosis and necroptosis with depletion of IAPs. Furthermore, ripoptosome, a prerequisite complex of necroptosis, was assembled and induced by VV-SMAC. In addition, the combination of VV-SMAC and vinblastine represented a synergistic effect on HCC cells. In summary, our data suggest that VV-SMAC is a potential candidate and combination of VV-SMAC and vinblastine may provide a new avenue in treatment of HCC. PMID:24771354

Pan, Qiang; Huang, Yuanyong; Chen, Lieyang; Gu, JinFa; Zhou, Xiumei

2014-10-01

264

Vaccinia virus entry/fusion complex subunit A28 is a target of neutralizing and protective antibodies  

SciTech Connect

The vaccinia virus entry/fusion complex (EFC) is comprised of at least eight transmembrane proteins that are conserved in all poxviruses. However, neither the physical structure of the EFC nor the immunogenicity of the individual components has been determined. We prepared soluble forms of two EFC components, A28 and H2, by replacing the transmembrane domain with a signal peptide and adding a polyhistidine tail. The proteins were expressed by baculoviruses, secreted from insect cells, purified by affinity chromatography and used to raise antibodies in rabbits. The antibodies recognized the viral proteins but only the antibody to recombinant A28 bound intact virions and neutralized infectivity. Analyses with a set of overlapping peptides revealed a neutralizing epitope between residues 73 and 92 of A28. Passive immunization of mice with IgG purified from the anti-A28 serum provided partial protection against a vaccinia virus intranasal challenge, whereas IgG from the anti-H2 serum did not.

Nelson, Gretchen E.; Sisler, Jerry R.; Chandran, Dev [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3210 (United States); Moss, Bernard [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-3210 (United States)], E-mail: bmoss@nih.gov

2008-10-25

265

Structure of vaccinia virus A46, an inhibitor of TLR4 signaling pathway, shows the conformation of VIPER motif.  

PubMed

Vaccinia virus (VACV) encodes many proteins that interfere with the host immune system. Vaccinia virus A46 protein specifically targets the BB-loop motif of TIR-domain-containing proteins to disrupt receptor:adaptor (e.g., TLR4:MAL and TLR4:TRAM) interactions of the toll-like receptor signaling. The crystal structure of A46 (75-227) determined at 2.58 Ĺ resolution showed that A46 formed a homodimer and adopted a Bcl-2-like fold similar to other VACV proteins such as A52, B14, and K7. Our structure also revealed that VIPER (viral inhibitory peptide of TLR4) motif resides in the ?1-helix and six residues of the VIPER region were exposed to surface for binding to target proteins. In vitro binding assays between wild type and six mutants A46 (75-227) and full-length MAL identified critical residues in the VIPER motif. Computational modeling of the A46:MAL complex structure showed that the VIPER region of A46 and AB loop of MAL protein formed a major binding interface. In summary, A46 is a homodimer with a Bcl-2-like fold and VIPER motif is believed to be involved in the interaction with MAL protein based on our binding assays. PMID:24723367

Kim, Yongwoon; Lee, Hasup; Heo, Lim; Seok, Chaok; Choe, Jungwoo

2014-07-01

266

9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.  

Code of Federal Regulations, 2013 CFR

...Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus...Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed...

2013-01-01

267

9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.  

...Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus...Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed...

2014-01-01

268

9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.  

Code of Federal Regulations, 2011 CFR

...Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus...Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed...

2011-01-01

269

9 CFR 113.207 - Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus.  

Code of Federal Regulations, 2012 CFR

...Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus...Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed Virus. Encephalomyelitis Vaccine, Eastern, Western, and Venezuelan, Killed...

2012-01-01

270

Biochem. J. (2009) 420, 2735 (Printed in Great Britain) doi:10.1042/BJ20082296 27 Characterization of the vaccinia virus D10 decapping enzyme provides  

E-print Network

of the vaccinia virus D10 decapping enzyme provides evidence for a two-metal-ion mechanism Marie F. SOULI Decapping enzymes are required for the removal of the 5 -end cap of mRNAs. These enzymes exhibit a specific m7 GDP and monophosphorylated RNA products. Decapping enzymes have been found in humans, plants

Perreault, Jean-Pierre

271

Protection of IFNAR (-/-) Mice against Bluetongue Virus Serotype 8, by Heterologous (DNA/rMVA) and Homologous (rMVA/rMVA) Vaccination, Expressing Outer-Capsid Protein VP2  

PubMed Central

The protective efficacy of recombinant vaccines expressing serotype 8 bluetongue virus (BTV-8) capsid proteins was tested in a mouse model. The recombinant vaccines comprised plasmid DNA or Modified Vaccinia Ankara viruses encoding BTV VP2, VP5 or VP7 proteins. These constructs were administered alone or in combination using either a homologous prime boost vaccination regime (rMVA/rMVA) or a heterologous vaccination regime (DNA/rMVA). The DNA/rMVA or rMVA/rMVA prime-boost were administered at a three week interval and all of the animals that received VP2 generated neutralising antibodies. The vaccinated and non-vaccinated-control mice were subsequently challenged with a lethal dose of BTV-8. Mice vaccinated with VP7 alone were not protected. However, mice vaccinated with DNA/rMVA or rMVA/rMVA expressing VP2, VP5 and VP7 or VP2 alone were all protected. PMID:23593251

Jabbar, Tamara Kusay; Calvo-Pinilla, Eva; Mateos, Francisco; Gubbins, Simon; Bin-Tarif, Abdelghani; Bachanek-Bankowska, Katarzyna; Alpar, Oya; Ortego, Javier; Takamatsu, Haru-Hisa; Mertens, Peter Paul Clement; Castillo-Olivares, Javier

2013-01-01

272

Expert Rev Vaccines . Author manuscript Development of hepatitis C virus vaccines: challenges and progress  

E-print Network

Expert Rev Vaccines . Author manuscript Page /1 14 Development of hepatitis C virus vaccines of an effective vaccine against hepatitis C virus (HCV) has long been defined as a difficult challenge due infection. Studies investigating prophylactic vaccine approaches in chimpanzees have confirmed

Paris-Sud XI, Université de

273

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy  

PubMed Central

Background Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. PMID:22236378

2012-01-01

274

An etoposide-induced block in vaccinia virus telomere resolution is dependent on the virus-encoded DNA ligase.  

PubMed Central

Etoposide, an inhibitor of the breakage-reunion reaction associated with cellular type II DNA topoisomerases, was shown to inhibit plaque formation of vaccinia virus. This drug had a major effect on the segregation of newly replicated DNA concatemers. Gene expression and the initiation and elongation phases of viral DNA replication were essentially unaffected. Pulsed-field gel electrophoresis of viral DNA replicated in the presence of etoposide revealed two major classes of DNA: the mature monomeric linear genome and DNA that failed to enter the gel (the relative proportions depending on the concentrations of drug). Restriction enzyme analysis showed a severe defect in telomere resolution. In addition, slowly migrating restriction fragments were suggestive of a general recombination defect. We have isolated several etoposide-resistant mutants and used marker rescue and DNA sequencing to localize the resistance-causing mutation to the amino terminus of the viral DNA ligase gene. Inactivation of the DNA ligase also resulted in an etoposide-resistant phenotype, but to a lesser extent. The telomere resolution and segregation defects were corrected both in the drug-resistant mutants and in the DNA ligase knockout mutants. Reinsertion of wild-type or mutant DNA ligase in the viral thymidine kinase locus confirmed the role of the viral DNA ligase in conferring sensitivity not only to etoposide but also to another topoisomerase II inhibitor, 4'-(9-acridinylamino) methanesulphon-m-anisidide (mAMSA). The data suggest that the nonessential DNA ligase is involved in telomere resolution, possibly as part of a general recombinase. PMID:7884854

DeLange, A M; Carpenter, M S; Choy, J; Newsway, V E

1995-01-01

275

Local control of repeated-dose rectal challenges in DNA/MVA-vaccinated macaques protected against a first series of simian immunodeficiency virus challenges.  

PubMed

Here, we report the results of a late boost and three additional series of simian immunodeficiency virus (SIV) challenges in seven DNA/modified vaccinia virus Ankara (MVA)-vaccinated rhesus macaques who resisted a first series of rectal challenges. During 29 additional challenges delivered over 2.3 years, all animals became infected. However, 13 blips of virus in six macaques and anamnestic Env-specific rectal IgA responses in three of the six suggested that local control of infections was occurring during the serial challenge. PMID:24574408

Kannanganant, Sunil; Gangadhara, Salaija; Lai, Lilin; Lawson, Benton; Kozlowski, Pamela A; Robinson, Harriet L; Amara, Rama Rao

2014-05-01

276

Induction of Multifunctional Human Immunodeficiency Virus Type 1 (HIV1)Specific T Cells Capable of Proliferation in Healthy Subjects by Using a Prime-Boost Regimen of DNA and Modified Vaccinia Virus Ankara-Vectored Vaccines Expressing HIV1 Gag Coupled to CD8+ T-Cell Epitopes  

Microsoft Academic Search

vaccination in both ex vivo gamma interferon (IFN-) ELISPOT (group mean, 210 spot-forming cells\\/106 cells) and proliferation (group mean stimulation index, 37), with assays detecting positive responses in four out of eight and five out of eight subjects, respectively. No HIV-1-specific T-cell responses were detected in either assay in the 2 MVA.HIVA group or subjects receiving placebo. Using a highly

Nilu Goonetilleke; Stephen Moore; Len Dally; Nicola Winstone; Inese Cebere; Abdul Mahmoud; Susana Pinheiro; Geraldine Gillespie; Denise Brown; Vanessa Loach; Joanna Roberts; Ana Guimaraes-Walker; Peter Hayes; Kelley Loughran; Carole Smith; Jan De Bont; Carl Verlinde; Danii Vooijs; Claudia Schmidt; Mark Boaz; Jill Gilmour; Pat Fast; Lucy Dorrell; Tomas Hanke; Andrew J. McMichael

2006-01-01

277

Yellow fever vector live-virus vaccines: West Nile virus vaccine development  

Microsoft Academic Search

By combining molecular-biological techniques with our increased understanding of the effect of gene sequence modification on viral function, yellow fever 17D, a positive-strand RNA virus vaccine, has been manipulated to induce a protective immune response against viruses of the same family (e.g. Japanese encephalitis and dengue viruses). Triggered by the emergence of West Nile virus infections in the New World

Juan Arroyo; Charles A Miller; John Catalan; Thomas P Monath

2001-01-01

278

Ebola Virus: Immune Mechanisms of Protection and Vaccine Development  

Microsoft Academic Search

Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has

Adeline M. Nyamathi; John L. Fahey; Heather Sands; Adrian M. Casillas

2003-01-01

279

Type I interferon mimetics bypass vaccinia virus decoy receptor virulence factor for protection of mice against lethal infection.  

PubMed

The canonical model of interferon (IFN) signaling focuses solely on the activation of STAT transcription factors which, according to the model, are initiated by the singular event of cross-linkage of the receptor extracellular domain by the IFN. The IFN has no further function beyond this. The model thus provides no approach to circumventing poxviruses decoy receptors that compete with the IFN receptors for IFNs. This simple event has allowed smallpox virus to decimate human populations throughout the ages. We have developed a noncanonical model of IFN signaling that has resulted in the development of small peptide mimetics to both types I and II IFNs. In this report, we focus on a type I IFN mimetic at positions 152 to 189, IFN-?1(152-189), which corresponds to the C terminus of human IFN-?1. This mimetic functions intracellularly and is thus not recognized by the B18R vaccinia virus decoy receptor. Mimetic synthesized with an attached palmitate (lipo-) for cell penetration protects mice from a lethal dose of vaccinia virus, while the parent IFN-?1 is ineffective. Unlike IFN-?1, the mimetic does not bind to the B18R decoy receptor. It further differs from the parent IFN in that it lacks the toxicity of weight loss and bone marrow suppression in mice while at the same time possessing a strong adjuvant effect on the immune system. The mimetic is thus an innate and adaptive immune regulator that is evidence of the dynamic nature of the noncanonical model of IFN signaling, in stark contrast to the canonical or classical model of signaling. PMID:24964806

Ahmed, Chulbul M; Johnson, Howard M

2014-08-01

280

Inhibition of the Ubiquitin-Proteasome System Prevents Vaccinia Virus DNA Replication and Expression of Intermediate and Late Genes?  

PubMed Central

The ubiquitin-proteasome system has a central role in the degradation of intracellular proteins and regulates a variety of functions. Viruses belonging to several different families utilize or modulate the system for their advantage. Here we showed that the proteasome inhibitors MG132 and epoxomicin blocked a postentry step in vaccinia virus (VACV) replication. When proteasome inhibitors were added after virus attachment, early gene expression was prolonged and the expression of intermediate and late genes was almost undetectable. By varying the time of the removal and addition of MG132, the adverse effect of the proteasome inhibitors was narrowly focused on events occurring 2 to 4 h after infection, the time of the onset of viral DNA synthesis. Further analyses confirmed that genome replication was inhibited by both MG132 and epoxomicin, which would account for the effect on intermediate and late gene expression. The virus-induced replication of a transfected plasmid was also inhibited, indicating that the block was not at the step of viral DNA uncoating. UBEI-41, an inhibitor of the ubiquitin-activating enzyme E1, also prevented late gene expression, supporting the role of the ubiquitin-proteasome system in VACV replication. Neither the overexpression of ubiquitin nor the addition of an autophagy inhibitor was able to counter the inhibitory effects of MG132. Further studies of the role of the ubiquitin-proteasome system for VACV replication may provide new insights into virus-host interactions and suggest potential antipoxviral drugs. PMID:19129442

Satheshkumar, P. S.; Anton, Luis C.; Sanz, Patrick; Moss, Bernard

2009-01-01

281

Ebola virus: from discovery to vaccine  

Microsoft Academic Search

Ebola virus, being highly pathogenic for humans and non-human primates and the subject of former weapons programmes, is now one of the most feared pathogens worldwide. In addition, the lack of pre- and post-exposure interventions makes the development of rapid diagnostics, new antiviral agents and protective vaccines a priority for many nations. Further insight into the ecology, immunology and pathogenesis

Steven Jones; Hans-Dieter Klenk; Hans-Joachim Schnittler; Heinz Feldmann

2003-01-01

282

Kinetics and intracellular location of intramolecular disulfide bond formation mediated by the cytoplasmic redox system encoded by vaccinia virus  

SciTech Connect

Poxviruses encode a redox system for intramolecular disulfide bond formation in cytoplasmic domains of viral proteins. Our objectives were to determine the kinetics and intracellular location of disulfide bond formation. The vaccinia virus L1 myristoylated membrane protein, used as an example, has three intramolecular disulfide bonds. Reduced and disulfide-bonded forms of L1 were distinguished by electrophoretic mobility and reactivity with monoclonal and polyclonal antibodies. Because disulfide bonds formed during 5 min pulse labeling with radioactive amino acids, a protocol was devised in which dithiothreitol was present at this step. Disulfide bond formation was detected by 2 min after removal of reducing agent and was nearly complete in 10 min. When the penultimate glycine residue was mutated to prevent myristoylation, L1 was mistargeted to the endoplasmic reticulum and disulfide bond formation failed to occur. These data suggested that viral membrane association was required for oxidation of L1, providing specificity for the process.

Bisht, Himani; Brown, Erica [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20894 (United States); Moss, Bernard, E-mail: bmoss@nih.go [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20894 (United States)

2010-03-15

283

Nasal DNA-MVA SIV vaccination provides more significant protection from progression to AIDS than a similar intramuscular vaccination  

Microsoft Academic Search

Preventive human immunodeficiency virus (HIV) vaccination may require induction of virus-specific immune responses at mucosal sites to contain viral infection locally after exposure, as most HIV infections occur through mucosal surfaces. We compared the efficacy of an intranasal or intramuscular Simian immunodeficiency virus (SIV)+ interleukin (IL)-2+IL-15 DNA\\/SIV–MVA (modified vaccinia virus Ankara) vaccination in preventing disease progression in SIVmac251 intrarectally challenged

M Manrique; PA Kozlowski; S-W Wang; RL Wilson; E Micewicz; DC Montefiori; KG Mansfield; A Carville; A Aldovini

2009-01-01

284

Human Immunodeficiency Virus Vaccine Trials  

PubMed Central

More than 2 million AIDS-related deaths occurred globally in 2008, and more than 33 million people are living with HIV/AIDS. Despite promising advances in prevention, an estimated 2.7 million new HIV infections occurred in that year, so that for every two patients placed on combination antiretroviral treatment, five people became infected. The pandemic poses a formidable challenge to the development, progress, and stability of global society 30 years after it was recognized. Experimental preventive HIV-1 vaccines have been administered to more than 44,000 human volunteers in more than 187 separate trials since 1987. Only five candidate vaccine strategies have been advanced to efficacy testing. The recombinant glycoprotein (rgp)120 subunit vaccines, AIDSVAX B/B and AIDSVAX B/E, and the Merck Adenovirus serotype (Ad)5 viral-vector expressing HIV-1 Gag, Pol, and Nef failed to show a reduction in infection rate or lowering of postinfection viral set point. Most recently, a phase III trial that tested a heterologous prime-boost vaccine combination of ALVAC-HIV vCP1521 and bivalent rgp120 (AIDSVAX B/E) showed 31% efficacy in protection from infection among community-risk Thai participants. A fifth efficacy trial testing a DNA/recombinant(r) Ad5 prime-boost combination is currently under way. We review the clinical trials of HIV vaccines that have provided insight into human immunogenicity or efficacy in preventing HIV-1 infection. PMID:23209178

O’Connell, Robert J.; Kim, Jerome H.; Corey, Lawrence; Michael, Nelson L.

2012-01-01

285

Analysis of bovine herpesvirus 1 glycoprotein gIV truncations and deletions expressed by recombinant vaccinia viruses.  

PubMed Central

Glycoprotein gIV is an envelope component of bovine herpesvirus type 1 and appears to be involved in attachment, penetration, and cell fusion. Four antigenic domains which include both continuous and discontinuous epitopes have been previously defined by competition binding assays using gIV-specific monoclonal antibodies (MAbs). Here we describe the construction of C-terminal truncations and internal deletions in the gIV-encoding gene and analyses of the effects of these mutations on the synthesis, processing, transport, and antigenicity of glycoprotein gIV as expressed by recombinant vaccinia viruses. Wild-type gIV expressed by recombinant vaccinia virus STgIV was indistinguishable from authentic gIV produced in bovine herpesvirus 1-infected cells with respect to molecular weight, processing, transport, and antigenicity. Analysis of the mutant proteins showed that the binding sites for MAbs 9D6 and 3D9S, which recognize linear epitopes, lie between amino acids 164 and 216 and amino acids 320 and 355, respectively. Discontinuous epitopes recognized by MAbs 3E7, 4C1, 2C8, and 3C1 were located between amino acids 19 and 320, whereas amino acids 320 to 355 were critical for binding of MAb 136. All mutant proteins containing amino acids 245 to 320 were processed, possess endo-beta-N-acetylglucosaminidase H-resistant oligosaccharides, and were transported to the cell surface or secreted into the medium. In contrast, mutant proteins missing amino acids 245 to 320 were retained in the rough endoplasmic reticulum. These findings suggest that residues 245 to 320 are important for proper processing and transport of gIV to the cell surface. Images PMID:8383232

Tikoo, S K; Zamb, T J; Babiuk, L A

1993-01-01

286

Genetically Engineered Mengo Virus Vaccination of Multiple Captive Wildlife Species  

Microsoft Academic Search

Encephalomyocarditis virus (EMCV), has caused the deaths of many species of animals in zoological parks and research institutions. The Audubon Park Zoo, (New Orleans, Louisiana, USA) attempted vaccination of several species with a killed EMCV vaccine with mixed results. This paper reports an attempt at vaccination against EMCV using a genetically engineered, live attenuated Mengo virus (vMC0) at the Au-

Kay A. Backues; Marchel Hill; Ann C. Palmenberg; Christine Miller; Kenneth F. Soike

287

The Amino Terminus of the Vaccinia Virus E3 Protein Is Necessary To Inhibit the Interferon Response  

PubMed Central

Vaccinia virus (VACV) encodes a multifunctional protein, E3L, that is necessary for interferon (IFN) resistance in cells in culture. Interferon resistance has been mapped to the well-characterized carboxy terminus of E3L, which contains a conserved double-stranded RNA binding domain. The amino terminus of E3L has a Z-form nucleic acid binding domain, which has been shown to be dispensable for replication and IFN resistance in HeLa and RK13 cells; however, a virus expressing E3L deleted of the amino terminus has reduced pathogenicity in an animal model. In this study, we demonstrate that the pathogenicity of a virus expressing E3L deleted of the amino terminus was fully rescued in type I IFN receptor knockout (IFN-?/?R?/?) mice. Furthermore, this virus was IFN sensitive in primary mouse embryo fibroblasts (MEFs). This virus induced the phosphorylation of the ? subunit of eukaryotic initiation factor 2 (eIF2?) in MEFs in an IFN-dependent manner. The depletion of double-stranded RNA-dependent protein kinase (PKR) from these MEFs restored the IFN resistance of this virus. Furthermore, the virus expressing E3L deleted of the amino terminus was also IFN resistant in PKR?/? MEFs. Thus, our data demonstrate that the amino terminus of E3L is necessary to inhibit the type I IFN response both in mice and in MEFs and that in MEFs, the amino terminus of E3L functions to inhibit the PKR pathway. PMID:22419806

White, Stacy D.

2012-01-01

288

Progress towards a hepatitis C virus vaccine  

PubMed Central

New drugs to treat hepatitis C are expected to be approved over the next few years which promise to cure nearly all patients. However, due to issues of expected drug resistance, suboptimal activity against diverse hepatitis C virus (HCV) genotypes and especially because of their extremely high cost, it is unlikely that these HCV drugs will substantially reduce the world's HCV carrier population of around 170 million in the near future or the estimated global incidence of millions of new HCV infections. For these reasons, there is an urgent need to develop a prophylactic HCV vaccine and also to determine if therapeutic vaccines can aid in the treatment of chronically infected patients. After much early pessimism on the prospects for an effective prophylactic HCV vaccine, our recent knowledge of immune correlates of protection combined with the demonstrated immunogenicity and protective animal efficacies of various HCV vaccine candidates now allows for realistic optimism. This review summarizes the current rationale and status of clinical and experimental HCV vaccine candidates based on the elicitation of cross-neutralizing antibodies and broad cellular immune responses to this highly diverse virus.

Man John Law, Lok; Landi, Abdolamir; Magee, Wendy C; Lorne Tyrrell, D; Houghton, Michael

2013-01-01

289

Vaccinia virus-mediated intra-tumoral expression of matrix metalloproteinase 9 enhances oncolysis of PC-3 xenograft tumors  

PubMed Central

Background Oncolytic viruses, including vaccinia virus (VACV), are a promising alternative to classical mono-cancer treatment methods such as surgery, chemo- or radiotherapy. However, combined therapeutic modalities may be more effective than mono-therapies. In this study, we enhanced the effectiveness of oncolytic virotherapy by matrix metalloproteinase (MMP-9)-mediated degradation of proteins of the tumoral extracellular matrix (ECM), leading to increased viral distribution within the tumors. Methods For this study, the oncolytic vaccinia virus GLV-1h255, containing the mmp-9 gene, was constructed and used to treat PC-3 tumor-bearing mice, achieving an intra-tumoral over-expression of MMP-9. The intra-tumoral MMP-9 content was quantified by immunohistochemistry in tumor sections. Therapeutic efficacy of GLV-1h255 was evaluated by monitoring tumor growth kinetics and intra-tumoral virus titers. Microenvironmental changes mediated by the intra-tumoral MMP-9 over-expression were investigated by microscopic quantification of the collagen IV content, the blood vessel density (BVD) and the analysis of lymph node metastasis formation. Results GLV-1h255-treatment of PC-3 tumors led to a significant over-expression of intra-tumoral MMP-9, accompanied by a marked decrease in collagen IV content in infected tumor areas, when compared to GLV-1h68-infected tumor areas. This led to considerably elevated virus titers in GLV-1h255 infected tumors, and to enhanced tumor regression. The analysis of the BVD, as well as the lumbar and renal lymph node volumes, revealed lower BVD and significantly smaller lymph nodes in both GLV-1h68- and GLV-1h255- injected mice compared to those injected with PBS, indicating that MMP-9 over-expression does not alter the metastasis-reducing effect of oncolytic VACV. Conclusions Taken together, these results indicate that a GLV-1h255-mediated intra-tumoral over-expression of MMP-9 leads to a degradation of collagen IV, facilitating intra-tumoral viral dissemination, and resulting in accelerated tumor regression. We propose that approaches which enhance the oncolytic effect by increasing the intra-tumoral viral load, may be an effective way to improve therapeutic outcome. PMID:22917220

2012-01-01

290

Structure Function Studies of Vaccinia Virus Host Range Protein K1 Reveal a Novel Functional Surface for Ankyrin Repeat Proteins  

SciTech Connect

Poxvirus host tropism at the cellular level is regulated by virus-encoded host range proteins acting downstream of virus entry. The functioning mechanisms of most host range proteins are unclear, but many contain multiple ankyrin (ANK) repeats, a motif that is known for ligand interaction through a concave surface. We report here the crystal structure of one of the ANK repeat-containing host range proteins, the vaccinia virus K1 protein. The structure, at a resolution of 2.3 {angstrom}, showed that K1 consists entirely of ANK repeats, including seven complete ones and two incomplete ones, one each at the N and C terminus. Interestingly, Phe82 and Ser83, which were previously shown to be critical for K1's function, are solvent exposed and located on a convex surface, opposite the consensus ANK interaction surface. The importance of this convex surface was further supported by our additional mutagenesis studies. We found that K1's host range function was negatively affected by substitution of either Asn51 or Cys47 and completely abolished by substitution of both residues. Cys47 and Asn51 are also exposed on the convex surface, spatially adjacent to Phe82 and Ser83. Altogether, our data showed that K1 residues on a continuous convex ANK repeat surface are critical for the host range function, suggesting that K1 functions through ligand interaction and does so with a novel ANK interaction surface.

Li, Yongchao; Meng, Xiangzhi; Xiang, Yan; Deng, Junpeng (Texas-HSC); (OKLU)

2010-06-15

291

Vaccination of Macaques against Pathogenic Simian Immunodeficiency Virus with Venezuelan Equine Encephalitis Virus Replicon Particles  

Microsoft Academic Search

Vaccine vectors derived from Venezuelan equine encephalitis virus (VEE) that expressed simian immuno- deficiency virus (SIV) immunogens were tested in rhesus macaques as part of the effort to design a safe and effective vaccine for human immunodeficiency virus. Immunization with VEE replicon particles induced both humoral and cellular immune responses. Four of four vaccinated animals were protected against disease for

NANCY L. DAVIS; IAN J. CALEY; KEVIN W. BROWN; MICHAEL R. BETTS; DAVID M. IRLBECK; KATHRYN M. MCGRATH; MARY J. CONNELL; DAVID C. MONTEFIORI; JEFFREY A. FRELINGER; RONALD SWANSTROM; PHILIP R. JOHNSON; ROBERT E. JOHNSTON

2000-01-01

292

9 CFR 113.213 - Pseudorabies Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

... (i) Ten pseudorabies susceptible pigs (five vaccinates and five controls...300 TCID50 of virus shall be used. Pigs shall be considered susceptible if there...Service may be used. (iii) The five pigs used as vaccinates shall be...

2010-01-01

293

Antivirally Protective Cytotoxic T Cell Memory to Lymphocytic Choriomeningitis Virus Is Governed by  

Microsoft Academic Search

Summary The basis of antiviral protection by memory cytotoxic T lymphocytes (CTL) was investigated in vivo and in vitro using lymphocytic choriomeningitis virus (LCMV) and recombinant vaccinia viruses expressing the LCMVglycoprotein (vacc-GP) or -nucleoprotein (vacc-NP) . The widely replicating LCMV with a tendency to persist induced solid long-term protective memory. The poorly replicating vaccinia recombinant viruses revealed in the vaccinated

Stephan Oehen; Hanspeter Waldner; Thomas M. Kundig; Hans Hengartner; Rolf M. Zinkernagel

294

Interaction between the J3R Subunit of Vaccinia Virus Poly(A) Polymerase and the H4L Subunit of the Viral RNA Polymerase  

Microsoft Academic Search

J3R, the 39-kDa subunit of vaccinia virus poly(A) polymerase, is a multifunctional protein that catalyzes (nucleoside-2?-O-)-methyltransferase activity, serves as a poly(A) polymerase stimulatory factor, and acts as a postreplicative positive transcription elongation factor. Prior results support an association between poly(A) polymerase and the virion RNA polymerase. A possible direct interaction between J3R and H4L subunit of virion RNA polymerase was

Mohamed Ragaa Mohamed; Donald R. Latner; Richard C. Condit; Edward G. Niles

2001-01-01

295

Effect of serum type and concentration on the expression of ? -galactosidase in recombinant vaccinia virus infected HeLa S3 cells  

Microsoft Academic Search

The effect of serum type and concentration on recombinant protein expression in vaccinia virus infected HeLa S3 cells was studied in both static and suspension culture. A model heterologous protein,ß-galactosidase (ß-gal), was used. Calf and horse sera in the range of 0.5–10%(v\\/v) were investigated. In static culture, the calf serum concentration did not show any significant influence on the ß-gal

Seung Chul Jun; Gyun Min Lee; Su Hwan Chang; Jung Hoe Kim

1995-01-01

296

A recombinant vaccinia virus encoding human papillomavirus types 16 and 18, E6 and E7 proteins as immunotherapy for cervical cancer  

Microsoft Academic Search

SummaryBackground Human papillomavirus (HPV) infection, especially with type 16 or 18, is associated with cervical cancer. Two HPV proteins, E6 and E7, are consistently expressed in tumour cells. The objectives of the study were to examine the clinical and environmental safety and immunogenicity in the first clinical trial of a live recombinant vaccinia virus expressing the E6 and E7 proteins

L. K Borysiewicz; A Fiander; M Nimako; S Man; G. W. G Wilkinson; D Westmoreland; A. S Evans; M Adams; S. N Stacey; M. E. G Boursnell; E Rutherford; J. K Hickling; S. C Inglis

1996-01-01

297

Molecular Smallpox Vaccine Delivered by Alphavirus Replicons Elicits Protective Immunity in Mice and Non-human Primates  

PubMed Central

Naturally occurring smallpox was eradicated as a result of successful vaccination campaigns during the 1960s and 70s. Because of its highly contagious nature and high mortality rate, smallpox has significant potential as a biological weapon. Unfortunately, the current vaccine for orthopoxviruses is contraindicated for large portions of the population. Thus, there is a need for new, safe, and effective orthopoxvirus vaccines. Alphavirus replicon vectors, derived from strains of Venezuelan equine encephalitis virus, are being used to develop alternatives to the current smallpox vaccine. Here, we demonstrated that virus-like replicon particles (VRP) expressing the vaccinia virus A33R, B5R, A27L, and L1R genes elicited protective immunity in mice comparable to vaccination with live-vaccinia virus. Furthermore, cynomolgus macaques vaccinated with a combination of the four poxvirus VRPs (4pox-VRP) developed antibody responses to each antigen. These antibody responses were able to neutralize and inhibit the spread of both vaccinia virus and monkeypox virus. Macaques vaccinated with 4pox-VRP, flu HA VRP (negative control), or live-vaccinia virus (positive control) were challenged intravenously with 5 × 106 PFU of monkeypox virus 1 month after the second VRP vaccination. Four of the six negative control animals succumbed to monkeypox and the remaining two animals demonstrated either severe or grave disease. Importantly, all 10 macaques vaccinated with the 4pox-VRP vaccine survived without developing severe disease. These findings revealed that a single-boost VRP smallpox vaccine shows promise as a safe alternative to the currently licensed live-vaccinia virus smallpox vaccine. PMID:19833247

Hooper, Jay W.; Ferro, Anthony M.; Golden, Joseph W.; Silvera, Peter; Dudek, Jeanne; Alterson, Kim; Custer, Max; Rivers, Bryan; Morris, John; Owens, Gary; Smith, Jonathan F.; Kamrud, Kurt I.

2009-01-01

298

Vaccination of rhesus macaques with a vif-deleted simian immunodeficiency virus proviral DNA vaccine  

PubMed Central

Studies in non-human primates, with simian immunodeficiency virus (SIV) and simian/human immunodeficiency virus (SHIV) have demonstrated that live-attenuated viral vaccines are highly effective; however these vaccine viruses maintain a low level of pathogenicity. Lentivirus attenuation associated with deletion of the viral vif gene carries a significantly reduced risk for pathogencity, while retaining the potential for virus replication of low magnitude in the host. This report describes a vif-deleted simian immunodeficiency virus (SIV)mac239 provirus that was tested as an attenuated proviral DNA vaccine by inoculation of female rhesus macaques. SIV-specific interferon-? enzyme-linked immunospot responses of low magnitude were observed after immunization with plasmid containing the vif-deleted SIV provirus. However, vaccinated animals displayed strong sustained virus-specific T cell proliferative responses and increasing antiviral antibody titers. These immune responses suggested either persistent vaccine plasmid expression or low level replication of vif-deleted SIV in the host. Immunized and unvaccinated macaques received a single high dose vaginal challenge with pathogenic SIVmac251. A transient suppression of challenge virus load and a greater median survival time was observed for vaccinated animals. However, virus loads for vaccinated and unvaccinated macaques were comparable by 20 weeks after challenge and overall survival curves for the two groups were not significantly different. Thus, a vif-deleted SIVmac239 proviral DNA vaccine is immunogenic and capable of inducing a transient suppression of pathogenic challenge virus, despite severe attenuation of the vaccine virus. PMID:18261756

Sparger, Ellen E.; Dubie, Robert A.; Shacklett, Barbara L.; Cole, Kelly S.; Chang, W. L. William; Luciw, Paul A.

2008-01-01

299

Experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses  

PubMed Central

Influenza A viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. While the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. Thus, there is need of improved influenza vaccines and vaccination strategies. This review discusses advances in alternative influenza vaccines, touching briefly on licensed vaccines and vaccine antigens; then reviewing recombinant subunit vaccines, virus-like particle vaccines and DNA vaccines, with the main focus on virus-vectored vaccine approaches. PMID:23440999

Mooney, Alaina J; Tompkins, S Mark

2013-01-01

300

ORAL VACCINATION OF RACCOONS (PROCYON LOTOR) WITH AN ATTENUATED (SAD-B19) RABIES VIRUS VACCINE  

Microsoft Academic Search

Unlike previous reports to the contrary, raccoons (Proc yon lotor) were successfully vaccinated against rabies with a liquid SAD-B19 attenuated virus vaccine administered per os and given in vaccine-laden baits. There was neither evidence of vaccine-induced rabies in raccoons nior mia limited safety trial with opossums (Dideiphis virginiana) given SAD-B19. Protection from lethal street rabies virus infection was not absolute:

C. E. Rupprecht; B. Dietzschold; J. H. Cox; L. G. Schneider

301

Efficacy and safety/toxicity study of recombinant vaccinia virus JX-594 in two immunocompetent animal models of glioma.  

PubMed

The purpose of this study was to investigate the oncolytic potential of the recombinant, granulocyte macrophage colony-stimulating factor (GM-CSF)-expressing vaccinia virus (VV) JX-594 in experimental malignant glioma (MGs) in vitro and in immunocompetent rodent models. We have found that JX-594 killed all MG cell lines tested in vitro. Intratumoral (i.t.) administration of JX-594 significantly inhibited tumor growth and prolonged survival in rats-bearing RG2 intracranial (i.c.) tumors and mice-bearing GL261 brain tumors. Combination therapy with JX-594 and rapamycin significantly increased viral replication and further prolonged survival in both immunocompetent i.c. MG models with several animals considered "cured" (three out of seven rats >120 days, terminated experiment). JX-594 infected and killed brain tumor-initiating cells (BTICs) from patient samples grown ex vivo, and did so more efficiently than other oncolytic viruses MYXV, Reovirus type-3, and VSV(?M51). Additional safety/toxicity studies in nontumor-bearing rodents treated with a supratherapeutic dose of JX-594 demonstrated GM-CSF-dependent inflammation and necrosis. These results suggest that i.c. administered JX-594 triggers a predictable GM-CSF-mediated inflammation in murine models. Before proceeding to clinical trials, JX-594 should be evaluated in the brains of nonhuman primates and optimized for the viral doses, delivery routes as well as the combination agents (e.g., mTOR inhibitors). PMID:20808290

Lun, XueQing; Chan, Jennifer; Zhou, Hongyuan; Sun, Beichen; Kelly, John J P; Stechishin, Owen Owen; Bell, John C; Parato, Kelley; Hu, Kang; Vaillant, Dominique; Wang, Jiahu; Liu, Ta-Chiang; Breitbach, Caroline; Kirn, David; Senger, Donna L; Forsyth, Peter A

2010-11-01

302

Characterization and evaluation of a new oncolytic Vaccinia Virus strain LIVP6.1.1 for canine cancer therapy  

PubMed Central

Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is one novel approach for canine cancer therapy. In this study we described for the first time the characterization and the use of new VACV strain LIVP6.1.1 as an oncolytic agent against canine cancer in a panel of four canine cancer cell lines including: soft tissue sarcoma (STSA-1), melanoma (CHAS), osteosarcoma (D-17) and prostate carcinoma (DT08/40). Cell culture data demonstrated that LIVP6.1.1 efficiently infected and destroyed all four tested canine cancer cell lines. In two different xenograft models on the basis of the canine soft tissue sarcoma STSA-1 and the prostate carcinoma DT08/40 cell lines, a systemic administration of the LIVP6.1.1 virus was found to be safe and led to anti-tumor and immunological effects resulting in the significant reduction of tumor growth in comparison to untreated control mice.   In summary, the pre-clinical evaluation has demonstrated the efficacy of LIVP6.1.1 for canine cancer therapy. Furthermore, a clinical trial with canine cancer patients has already been started. PMID:23093804

Gentschev, Ivaylo; Patil, Sandeep S.; Adelfinger, Marion; Weibel, Stephanie; Geissinger, Ulrike; Frentzen, Alexa; Chen, Nanhai G.; Yu, Yong A.; Zhang, Qian; Ogilvie, Gregory; Szalay, Aladar A.

2013-01-01

303

Regression of Established Human Papillomavirus Type 16 (HPV-16) Immortalized Tumors In Vivo by Vaccinia Viruses Expressing Different Forms of HPV-16 E7 Correlates with Enhanced CD8+ T-Cell Responses That Home to the Tumor Site  

PubMed Central

Using vaccinia virus as a live vector, we show that the expression of human papillomavirus type 16 (HPV-16) E7 fused to a nonhemolytic portion of the Listeria monocytogenes virulence factor, listeriolysin O (LLO), induces an immune response that causes the regression of established HPV-16 immortalized tumors in C57BL/6 mice. The vaccinia virus construct expressing LLO fused to E7 (VacLLOE7) was compared with two previously described vaccinia virus constructs: one that expresses unmodified E7 (VacE7) and another that expresses E7 in a form designed to direct it to intracellular lysosomal compartments and improve major histocompatibility complex class II-restricted responses (VacSigE7LAMP-1). C57BL/6 mice bearing established HPV-16 immortalized tumors of 5 or 8 mm were treated with each of these vaccines. Fifty percent of the mice treated with VacLLOE7 remained tumor free 2 months after tumor inoculation, whereas 12 to 25% of the mice were tumor free after treatment with VacSigE7LAMP-1 (depending on the size of the tumor). No mice were tumor free in the group given VacE7. Compared to VacE7, VacSigE7LAMP-1 and VacLLOE7 resulted in increased numbers of H2-Db-specific tetramer-positive CD8+ T cells in mouse spleens that produced gamma interferon and tumor necrosis factor alpha upon stimulation with RAHYNIVTF peptide. In addition, the highest frequency of tetramer-positive T cells was seen in the tumor sites of mice treated with VacLLOE7. An increased efficiency of E7-specific lysis by splenocytes from mice immunized with VacLLOE7 was also observed. These results indicate that the fusion of E7 with LLO not only enhances antitumor therapy by improving the tumoricidal function of E7-specific CD8+ T cells but may also increase the number of antigen-specific CD8+ T cells in the tumor, the principle site of antigen expression. PMID:11559797

Lamikanra, Abigail; Pan, Zhen-Kun; Isaacs, Stuart N.; Wu, Tzyy-Choou; Paterson, Yvonne

2001-01-01

304

New smallpox vaccines for an ancient scourge.  

PubMed

The potential use of variola virus, a Class A agent of bioterrorism, remains a concern. In an effort to prepare for a possible smallpox outbreak due to an intentional release of variola, the U.S. government and industry have been evaluating vaccines stored in the National Strategic Stockpile including cell culture grown ACAM2000 and modified vaccinia Ankara, IMVAMUNE, in clinical studies. This paper discusses smallpox vaccines studies conducted at the Saint Louis University Center for Vaccine Development. PMID:25211864

Frey, Sharon E

2014-01-01

305

Vaccine Shows Promise Against Mosquito-Borne Virus  

MedlinePLUS

... enable JavaScript. Vaccine Shows Promise Against Mosquito-Borne Virus Volunteers developed antibodies to chikungunya in first human ... to protect people from the mosquito-borne chikungunya virus has shown promise in its first human trial. " ...

306

Vaccinia virus N1L protein resembles a B cell lymphoma-2 (Bcl-2) family protein  

PubMed Central

Poxviruses encode immuno-modulatory proteins capable of subverting host defenses. The poxvirus vaccinia expresses a small 14-kDa protein, N1L, that is critical for virulence. We report the crystal structure of N1L, which reveals an unexpected but striking resemblance to host apoptotic regulators of the B cell lymphoma-2 (Bcl-2) family. Although N1L lacks detectable Bcl-2 homology (BH) motifs at the sequence level, we show that N1L binds with high affinity to the BH3 peptides of pro-apoptotic Bcl-2 family proteins in vitro, consistent with a role for N1L in modulating host antiviral defenses. PMID:17123957

Aoyagi, Mika; Zhai, Dayong; Jin, Chaofang; Aleshin, Alexander E.; Stec, Boguslaw; Reed, John C.; Liddington, Robert C.

2007-01-01

307

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.  

Code of Federal Regulations, 2013 CFR

...2013-01-01 2013-01-01 false Bovine Virus Diarrhea Vaccine, Killed Virus. 113.215 Section 113.215 Animals and...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS;...

2013-01-01

308

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Bovine Virus Diarrhea Vaccine, Killed Virus. 113.215 Section 113.215 Animals and...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS;...

2010-01-01

309

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.  

Code of Federal Regulations, 2011 CFR

...2011-01-01 2011-01-01 false Bovine Virus Diarrhea Vaccine, Killed Virus. 113.215 Section 113.215 Animals and...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS;...

2011-01-01

310

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.  

Code of Federal Regulations, 2012 CFR

...2012-01-01 2012-01-01 false Bovine Virus Diarrhea Vaccine, Killed Virus. 113.215 Section 113.215 Animals and...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS;...

2012-01-01

311

9 CFR 113.215 - Bovine Virus Diarrhea Vaccine, Killed Virus.  

...2014-01-01 2014-01-01 false Bovine Virus Diarrhea Vaccine, Killed Virus. 113.215 Section 113.215 Animals and...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS;...

2014-01-01

312

Attenuated Influenza Virus Vaccines with Modified NS1 Proteins  

Microsoft Academic Search

\\u000a The development of reverse genetics techniques allowing the rescue of influenza virus from plasmid DNA has opened up the possibility\\u000a of inserting mutations into the genome of this virus for the generation of novel live attenuated influenza virus vaccines.\\u000a Modifications introduced into the viral NS1 gene via reverse genetics have resulted in attenuated influenza viruses with promising\\u000a vaccine potential. One

Jüergen A. Richt; Adolfo García-Sastre

313

Polyadenylated RNA sequences from vaccinia virus-infected cells selectively inhibit translation in a cell-free system: structural properties and mechanism of inhibition.  

PubMed

The mechanism of vaccinia virus-induced selective inhibition of host cell protein synthesis was studied in a nonpermissive (Chinese hamster ovary, CHO) and in a permissive mouse cell line ( L cells). Small polyadenylated RNAs obtained from uninfected and infected cells were fractionated into six size classes by polyacrylamide gel electrophoresis. The RNAs from the first two largest fractions (greater than 500 nucleotide, nt) were translated into some low-molecular-weight polypeptides, whereas, the RNAs from the remaining fractions (400-500, 300-400, 200-300, and 100-200 nt) had no translational activity in reticulocyte lysates. When these nontranslating polyadenylated short sequences (POLADS) were added to the cell-free system together with HeLa cell mRNAs, translation was inhibited from 70%, by the 400- to 500-nt fraction, to about 20%, by the 100- to 200-nt fraction. The degree of inhibition of protein synthesis was clearly dependent on the size of POLADS. The translation of vaccinia virus mRNAs in the cell-free system was inhibited by about 25% with the 400- to 500-nt fraction, by 5% with the 300- to 400-nt fraction, while the smaller size POLADS had no inhibitory effect. The inhibition of HeLa cell and vaccinia virus mRNA translation by POLADS was reversed by the simultaneous addition of oligo(dT) to the cell-free system. POLADS were also obtained from uninfected cells, but they inhibited the translation of HeLa cell and vaccinia virus mRNAs to a much lesser extent. The removal of the poly(A) moiety from POLADS by treatment with ribonuclease H and oligo(dT) abolished their inhibitory effect on HeLa cell mRNA translation. The average length of the poly(A) tails of POLADS obtained from infected cells was longer than that of POLADS from normal cells. Inhibition of HeLa cell mRNA translation mediated by POLADS in the cell-free system was reversed (approximately 70%) by addition of crude initiation factors (ribosomal salt wash, RSW). Significantly, inhibition of translation of POLADS was reversed (greater than 90%) by addition of purified poly(A) binding protein (PAB). Purified initiation factor 4A (eIF-4A) also reversed this inhibition, but to a lesser extent than RSW and PAB. Our results show that the translation of vaccinia virus mRNAs is resistant to POLADS, suggesting that POLADS, by virtue of their long poly(A) tails, may sequester PAB and thus, play a role in selective inhibition. PMID:1700540

Su, M J; Bablanian, R

1990-12-01

314

Imaging Characteristics, Tissue Distribution, and Spread of a Novel Oncolytic Vaccinia Virus Carrying the Human Sodium Iodide Symporter  

PubMed Central

Introduction Oncolytic viruses show promise for treating cancer. However, to assess therapy and potential toxicity, a noninvasive imaging modality is needed. This study aims to determine the in vivo biodistribution, and imaging and timing characteristics of a vaccinia virus, GLV-1h153, encoding the human sodium iodide symporter (hNIS. Methods GLV-1h153 was modified from GLV-1h68 to encode the hNIS gene. Timing of cellular uptake of radioiodide 131I in human pancreatic carcinoma cells PANC-1 was assessed using radiouptake assays. Viral biodistribution was determined in nude mice bearing PANC-1 xenografts, and infection in tumors confirmed histologically and optically via Green Fluorescent Protein (GFP) and bioluminescence. Timing characteristics of enhanced radiouptake in xenografts were assessed via 124I-positron emission tomography (PET). Detection of systemic administration of virus was investigated with both 124I-PET and 99m-technecium gamma-scintigraphy. Results GLV-1h153 successfully facilitated time-dependent intracellular uptake of 131I in PANC-1 cells with a maximum uptake at 24 hours postinfection (P<0.05). In vivo, biodistribution profiles revealed persistence of virus in tumors 5 weeks postinjection at 109 plaque-forming unit (PFU)/gm tissue, with the virus mainly cleared from all other major organs. Tumor infection by GLV-1h153 was confirmed via optical imaging and histology. GLV-1h153 facilitated imaging virus replication in tumors via PET even at 8 hours post radiotracer injection, with a mean %ID/gm of 3.82±0.46 (P<0.05) 2 days after intratumoral administration of virus, confirmed via tissue radiouptake assays. One week post systemic administration, GLV-1h153-infected tumors were detected via 124I-PET and 99m-technecium-scintigraphy. Conclusion GLV-1h153 is a promising oncolytic agent against pancreatic cancer with a promising biosafety profile. GLV-1h153 facilitated time-dependent hNIS-specific radiouptake in pancreatic cancer cells, facilitating detection by PET with both intratumoral and systemic administration. Therefore, GLV-1h153 is a promising candidate for the noninvasive imaging of virotherapy and warrants further study into longterm monitoring of virotherapy and potential radiocombination therapies with this treatment and imaging modality. PMID:22912675

Haddad, Dana; Chen, Chun-Hao; Carlin, Sean; Silberhumer, Gerd; Chen, Nanhai G.; Zhang, Qian; Longo, Valerie; Carpenter, Susanne G.; Mittra, Arjun; Carson, Joshua; Au, Joyce; Gonen, Mithat; Zanzonico, Pat B.; Szalay, Aladar A.; Fong, Yuman

2012-01-01

315

Pathogenesis of Newcastle disease in vaccinated chickens: pathogenicity of isolated virus and vaccine effect on challenge of its virus.  

PubMed

The pathogenicity of Newcastle disease (ND) virus, isolated from ND outbreak in vaccinated chickens, was evaluated through experiments. The pathogenicity indexes (mean death time (MDT); 58 hr, intracerebral pathogenicity index (ICPI); 1.7 and intravenous pathogenicity index (IVPI); 2.51) indicated that the ND virus was velogenic. The ND virus caused lymphocytic necrosis in the spleen with fibrinous exudation and proliferation of macrophages, sinusoidal fibrin exudation in the liver, proliferation of macrophages in the lung, lymphocytic necrosis and depletion in the bursa of Fabricius, cecal tonsils and thymus, necrosis of bone marrow, tracheitis, conjunctivitis and necrosis of feather epithelial cells in specific-pathogen-free chickens. Immunohistochemically, ND virus antigens were seen in the lesions mentioned above. The ND virus could not induce the encephalitis and pancreatitis that were observed in the natural case of ND in vaccinated chickens. There was no clinical disease in vaccinated chickens after the challenge of the ND virus. In diluted ND vaccine experiments, chickens vaccinated with a high dilution of vaccine and then challenged with the ND virus showed clinical sign and mortality with pancreatic focal necrosis. Vaccine diluted with fresh tap water had no effect on protection against the challenge of the ND virus. This study suggests that improper vaccination may be involved in outbreaks of ND in vaccinated chickens. PMID:23966012

Nakamura, Kikuyasu; Ito, Mitsuru; Nakamura, Toshiki; Yamamoto, Yu; Yamada, Manabu; Mase, Masaji; Imai, Kunitoshi

2014-01-01

316

Chikungunya virus vaccine prepared by Tween-ether extraction.  

PubMed

Chikungunya virus vaccines prepared by Tween 80 and ether inactivation of virus grown in green monkey kidney cell cultures were shown to be as immunogenic as comparable Formalin-inactivated vaccines. Both types of vaccine stimulated hemagglutination-inhibiting, complement-fixing, and neutralizing antibody and afforded protection to mice against a live virus challenge. It was shown after Tween-ether treatment of chikungunya virus that the infectivity of the virus was lost and the hemagglutinin titer was increased. By characterization of the resultant hemagglutinin by sucrose and cesium chloride density gradient centrifugation, it was found that the extracted particle was smaller in size and greater in density than the parent virus particle. Removal of lipid may account for the alterations in the physical characteristics of the infectious virus particle. Conditions for treatment of chikungunya virus with Tween and ether were found that preserved high titers of hemagglutinin as well as the immunogenicity of the virus preparations. PMID:4985431

Eckels, K H; Harrison, V R; Hetrick, F M

1970-02-01

317

Although most vaccines against influenza virus are administered  

E-print Network

) muCOSAL vACCINES NKT cells help fight flu ReseaRch highlights NATuRe RevIewS | immunology vOLuMe 8Although most vaccines against influenza virus are administered parenterally, emerging evidence suggests that vaccination through the nasal route is more effective in providing protection against mul

Cai, Long

318

Vaccination against Moroccan strains of Newcastle disease virus  

Microsoft Academic Search

Different vaccination programmes commonly used in Moroccan poultry farms were tested for their capacity to protect chickens against two representative Moroccan strains of velogenic viscerotropic Newcastle disease virus under controlled conditions. All vaccination programmes protected the chickens against mortality and the inactivated vaccine gave the highest antibody titres and the best protection against respiratory symptoms.

J. G. Bell; M. Mouahid

1987-01-01

319

Adherence to Hepatitis B Virus Vaccination At Syringe Exchange Sites  

Microsoft Academic Search

Injection drug users (IDUs) are at high risk for hepatitis B virus (HBV); however, they often do not receive preventive vaccination. IDUs who use mobile health care services linked to a syringe exchange program in New Haven were rou- tinely screened for HBV, hepatitis C virus, and syphilis. Individuals without prior exposure to HBV were offered three-part vaccination series. Of

Frederick L. Altice; Robert D. Bruce; Mary R. Walton; Marta I. Buitrago

2005-01-01

320

Control of Influenza and Poliomyelitis with Killed Virus Vaccines  

ERIC Educational Resources Information Center

Discusses control of poliomyelitis and influenza by live and killed virus vaccines. Considered are the etiological agents, pathogenic mechanisms and epidemiology of each disease. Reviews recent scientific studies of the diseases. Recommends use of killed virus vaccines in controlling both diseases. (CS)

Salk, Jonas; Salk, Darrell

1977-01-01

321

Evolution of equine influenza virus in vaccinated horses.  

PubMed

Influenza A viruses are characterized by their ability to evade host immunity, even in vaccinated individuals. To determine how prior immunity shapes viral diversity in vivo, we studied the intra- and interhost evolution of equine influenza virus in vaccinated horses. Although the level and structure of genetic diversity were similar to those in naďve horses, intrahost bottlenecks may be more stringent in vaccinated animals, and mutations shared among horses often fall close to putative antigenic sites. PMID:23388708

Murcia, Pablo R; Baillie, Gregory J; Stack, J Conrad; Jervis, Carley; Elton, Debra; Mumford, Jennifer A; Daly, Janet; Kellam, Paul; Grenfell, Bryan T; Holmes, Edward C; Wood, James L N

2013-04-01

322

Recombinant vesicular stomatitis virus as an HIV1 vaccine vector  

Microsoft Academic Search

Recombinant vesicular stomatitis virus (rVSV) is currently under evaluation as a human immunodeficiency virus (HIV)-1 vaccine vector. The most compelling reasons to develop rVSV as a vaccine vector include a very low seroprevalence in humans, the ability to infect and robustly express foreign antigens in a broad range of cells, and vigorous growth in continuous cell lines used for vaccine

David K. Clarke; David Cooper; Michael A. Egan; R. Michael Hendry; Christopher L. Parks; Stephen A. Udem

2006-01-01

323

G: Occ Health/Paperwork/Forms/Seasonal InfluenzaVirusVaccine 9-9-11 Page 1 of 1 Seasonal Influenza Virus Vaccine 2011-2012 (INACTIVATED)  

E-print Network

G: Occ Health/Paperwork/Forms/Seasonal InfluenzaVirusVaccine 9-9-11 Page 1 of 1 Seasonal Influenza Virus Vaccine 2011-2012 (INACTIVATED) This vaccine contains no preservative Please print or type Last/dd/yy) Vaccination at No Charge Vaccination for $26.00 Charge Active University Faculty/Staff Spouse/Domestic Partner

Wechsler, Risa H.

324

Temperature-sensitive mutant in the vaccinia virus E6 protein produce virions that are transcriptionally inactive  

PubMed Central

The vaccinia virus E6R gene encodes a late protein that is packaged into virion cores. A temperature sensitive mutant was used to study the role of this protein in viral replicative cycle. Cts52 has a P226L missense mutation in the E6R gene, shows a two-log reduction in plaque formation, but displays normal patterns of gene expression, late protein processing and DNA replication during infection. Mutant virions produced at 40°C were similar in their morphology to wt virions grown at 40°C. The particle to infectivity ratio was 50 times higher in purified Cts52 grown at 40°C when compared to the mutant grown at permissive temperature. In vitro characterization of Cts-52 particles grown at 40 °C revealed no differences in protein composition or in DNA content and the mutant virions could bind and enter cells. However, core particles prepared from Cts52 grown at 40 °C failed to transcribe in vitro. Our results show that E6 in the virion has either a direct or an indirect role in viral transcription. PMID:20116822

Boyd, Olga; Strahl, Audra L.; Rodeffer, Carson; Condit, Richard C.; Moussatche, Nissin

2010-01-01

325

Advances in Virus-Like Particle Vaccines for Filoviruses  

PubMed Central

Ebola virus (EBOV) and Marburg virus (MARV) are among the deadliest human pathogens, with no vaccines or therapeutics available. Multiple vaccine platforms have been tested for efficacy as prophylactic pretreatments or therapeutics for prevention of filovirus hemorrhagic fever. Most successful vaccines are based on a virus-vectored approach expressing the protective glycoprotein (GP); protein-based subunit and DNA vaccines have been tested with moderate success. Virus-like particle (VLP) vaccines have realized promising results when tested in both rodents and nonhuman primates. VLPs rely on the natural properties of the viral matrix protein (VP) 40 to drive budding of filamentous particles that can also incorporate ?1 other filovirus protein, including GP, VP24, and nucleoprotein (NP). Filovirus VLP vaccines have used particles containing 2 or 3 (GP and VP40, with or without NP) viral proteins generated in either mammalian or insect cells. Early studies successfully demonstrated efficacy of bivalent VLP vaccines in rodents; more recent studies have shown the ability of the VLP vaccines containing GP, NP, and VP40 to confer complete homologous protection against Ebola virus and Marburg virus in a prophylactic setting against in macaques. This review will discuss published work to date regarding development of the VLP vaccines for prevention of lethal filovirus hemorrhagic fever. PMID:21987741

Aman, M. Javad

2011-01-01

326

Porcine reproductive and respiratory syndrome virus vaccines: current status and strategies to a universal vaccine.  

PubMed

Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of PRRS, the most significant infectious disease currently affecting swine industry worldwide. In the United States alone, the economic losses caused by PRRS amount to more than 560 million US dollars every year. Due to immune evasion strategies and the antigenic heterogeneity of the virus, current commercial PRRSV vaccines (killed-virus and modified-live vaccines) are of unsatisfactory efficacy, especially against heterologous infection. Continuous efforts have been devoted to develop better PRRSV vaccines. Experimental PRRSV vaccines, including live attenuated vaccines, recombinant vectors expressing PRRSV viral proteins, DNA vaccines and plant-made subunit vaccines, have been developed. However, the genetic and antigenic heterogeneity of the virus limits the value of almost all of the PRRSV vaccines tested. Developing a universal vaccine that can provide broad protection against circulating PRRSV strains has become a major challenge for current vaccine development. This paper reviews current status of PRRSV vaccine development and discusses strategies to develop a universal PRRSV vaccine. PMID:23343057

Hu, J; Zhang, C

2014-04-01

327

Sensitivity to ultraviolet radiation of Lassa, vaccinia, and Ebola viruses dried on surfaces  

Microsoft Academic Search

Germicidal UV (also known as UVC) provides a means to decontaminate infected environments as well as a measure of viral sensitivity\\u000a to sunlight. The present study determined UVC inactivation slopes (and derived D37 values) of viruses dried onto nonporous (glass) surfaces. The data obtained indicate that the UV resistance of Lassa virus\\u000a is higher than that of Ebola virus. The

Jose-Luis Sagripanti; C. David Lytle

2011-01-01

328

Probable Congenital Transmission of Reticuloendotheliosis Virus Caused by Vaccination with Contaminated Vaccines  

PubMed Central

Contaminated vaccine is one unexpected and potential origin of virus infection. In order to investigate the most likely cause of disease in a broiler breeder company of Shandong Province, all 17 batches of live-virus vaccines used in the affected flocks and 478 tissue samples were tested by dot-blot hybridization, nested PCR, and IFA. The results suggested the outbreak of disease was most probably due to the vaccination of REV-contaminated MD-CVI988/Rispens vaccines and ND-LaSota+IB-H120 vaccines. Furthermore, the REV was probably transmitted to the commercial chickens through congenital transmission. PMID:22912872

Zhu, Shufen; Guo, Wenlong; Sheng, Pengcheng; Wang, Zunmin; Zhao, Changliang; Zhao, Qingyou; Zhu, Ruiliang

2012-01-01

329

The vaccinia virus O1 protein is required for sustained activation of extracellular signal-regulated kinase 1/2 and promotes viral virulence.  

PubMed

Sustained activation of the Raf/MEK/extracellular signal-regulated kinase (ERK) pathway in infected cells has been shown to be crucial for full replication efficiency of orthopoxviruses in cell culture. In infected cells, this pathway is mainly activated by the vaccinia virus growth factor (VGF), an epidermal growth factor (EGF)-like protein. We show here that chorioallantois vaccinia virus Ankara (CVA), but not modified vaccinia virus Ankara (MVA), induced sustained activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in infected human 293 cells, although both viruses direct secretion of functional VGF. A CVA mutant lacking the O1L gene (CVA-?O1L) demonstrated that the O1 protein was required for sustained upregulation of the ERK1/2 pathway in 293 cells as well as in other mammalian cell lines. The highly conserved orthopoxvirus O1L gene encodes a predicted 78-kDa protein with a hitherto-unknown function. CVA-?O1L showed reduced plaque size and an attenuated cytopathic effect (CPE) in infected cell cultures and reduced virulence and spread from lungs to ovaries in intranasally infected BALB/c mice. Reinsertion of an intact O1L gene into MVA, which in its original form harbors a fragmented O1L open reading frame (ORF), restored ERK1/2 activation in 293 cells but did not increase replication and spread of MVA in human or other mammalian cell lines. Thus, the O1 protein was crucial for sustained ERK1/2 activation in CVA- and MVA-infected human cells, complementing the autocrine function of VGF, and enhanced virulence in vivo. PMID:22171261

Schweneker, Marc; Lukassen, Susanne; Späth, Michaela; Wolferstätter, Michael; Babel, Eveline; Brinkmann, Kay; Wielert, Ursula; Chaplin, Paul; Suter, Mark; Hausmann, Jürgen

2012-02-01

330

Influenza A virus hemagglutinin protein subunit vaccine elicits vaccine-associated enhanced respiratory disease in pigs.  

PubMed

Vaccine-associated enhanced respiratory disease (VAERD) can occur when pigs are challenged with heterologous virus in the presence of non-neutralizing but cross-reactive antibodies elicited by whole inactivated virus (WIV) vaccine. The aim of this study was to compare the effects of heterologous ?1-H1N2 influenza A virus (IAV) challenge of pigs after vaccination with 2009 pandemic H1N1 virus (H1N1pdm09) recombinant hemagglutinin (HA) subunit vaccine (HA-SV) or temperature-sensitive live attenuated influenza virus (LAIV) vaccine, and to assess the role of immunity to HA in the development of VAERD. Both HA-SV and LAIV vaccines induced high neutralizing antibodies to virus with homologous HA (H1N1pdm09), but not heterologous challenge virus (?1-H1N2). LAIV partially protected pigs, resulting in reduced virus shedding and faster viral clearance, as no virus was detected in the lungs by 5 days post infection (dpi). HA-SV vaccinated pigs developed more severe lung and tracheal lesions consistent with VAERD following challenge. These results demonstrate that the immune response against the HA protein alone is sufficient to cause VAERD following heterologous challenge. PMID:25077416

Rajăo, Daniela S; Loving, Crystal L; Gauger, Phillip C; Kitikoon, Pravina; Vincent, Amy L

2014-09-01

331

Feline immunodeficiency virus (FIV) vaccine efficacy and FIV neutralizing antibodies.  

PubMed

A HIV-1 tier system has been developed to categorize the various subtype viruses based on their sensitivity to vaccine-induced neutralizing antibodies (NAbs): tier 1 with greatest sensitivity, tier 2 being moderately sensitive, and tier 3 being the least sensitive to NAbs (Mascola et al., J Virol 2005; 79:10103-7). Here, we define an FIV tier system using two related FIV dual-subtype (A+D) vaccines: the commercially available inactivated infected-cell vaccine (Fel-O-Vax(®) FIV) and its prototype vaccine solely composed of inactivated whole viruses. Both vaccines afforded combined protection rates of 100% against subtype-A tier-1 FIVPet, 89% against subtype-B tier-3 FIVFC1, 61% against recombinant subtype-A/B tier-2 FIVBang, 62% against recombinant subtype-F'/C tier-3 FIVNZ1, and 40% against subtype-A tier-2 FIVUK8 in short-duration (37-41 weeks) studies. In long-duration (76-80 weeks) studies, the commercial vaccine afforded a combined protection rate of at least 46% against the tier-2 and tier-3 viruses. Notably, protection rates observed here are far better than recently reported HIV-1 vaccine trials (Sanou et al., The Open AIDS J 2012; 6:246-60). Prototype vaccine protection against two tier-3 and one tier-2 viruses was more effective than commercial vaccine. Such protection did not correlate with the presence of vaccine-induced NAbs to challenge viruses. This is the first large-scale (228 laboratory cats) study characterizing short- and long-duration efficacies of dual-subtype FIV vaccines against heterologous subtype and recombinant viruses, as well as FIV tiers based on in vitro NAb analysis and in vivo passive-transfer studies. These studies demonstrate that not all vaccine protection is mediated by vaccine-induced NAbs. PMID:23800540

Coleman, James K; Pu, Ruiyu; Martin, Marcus M; Noon-Song, Ezra N; Zwijnenberg, Raphael; Yamamoto, Janet K

2014-02-01

332

Virus-like particles in picornavirus vaccine development.  

PubMed

Virus-like particles (VLP), which are similar to natural virus particles but do not contain viral genes, have brought about significant breakthroughs in many research fields because of their unique advantages. The ordered repeating epitopes of VLP can induce immunity responses similar to those prompted by natural viral infection; thus, VLP vaccines are regarded as candidate alternatives to whole-virus vaccines. As picornavirus has serious impacts on human and animal health, the development of efficient and safe vaccines is a key endeavor in preventing virus infections. The characteristics of picornavirus capsid proteins allow the development of VLP vaccines. This paper investigates research scenarios and progress on picornavirus VLP vaccines with the aim of providing a reference for researchers focusing on virology and vaccinology. PMID:24647496

Dong, Hu; Guo, Hui-Chen; Sun, Shi-Qi

2014-05-01

333

Protection against filovirus infection: virus-like particle vaccines.  

PubMed

Significant progress has been made in vaccine development against infection by Ebola and Marburg viruses, members of the Filoviridae, which cause severe hemorrhagic fevers in humans with no effective treatment and a mortality rate of up to 90%. Several vaccine strategies have been shown to effectively protect immunized animals against filovirus infection. Among these candidate vaccine strategies, virus-like particles represent a promising approach and have been shown to protect small laboratory animals as well as nonhuman primates against lethal challenge by Ebola and/or Marburg viruses. This review briefly summarizes filovirus epidemiology and pathogenesis, and focuses on the discussion of recent advances in filovirus vaccine development and the current understanding of protective immune responses against filovirus infection with an emphasis on the progress and challenge of filovirus virus-like particle vaccine development. PMID:18393603

Yang, Chinglai; Ye, Ling; Compans, Richard W

2008-04-01

334

Varicella-zoster virus vaccine, successes and difficulties.  

PubMed

Despite intensive efforts in recent decades to develop preventive or therapeutic vaccines against diseases caused by herpes simplex virus (HSV), or varicella-zoster virus (VZV), members of the Alpha herpes virinae subfamily of human herpes viruses,a safe and efficient vaccine has been approved for commercial development only against VZV. The VZV vaccine contains a live attenuated strain, OKA. It consists of amixture of at least 13 subpopulations of viruses, all with deletions, insertions or mutations in the genome; the most common mutations are observed in the open reading frame 62 (ORF62). Experience over more than 30 years in Japan, the USA and other countries where VZV vaccination is provided has demonstrated that the vaccine is safe and the effectiveness of two doses compared to unvaccinated children is 98-99%. When administered in a higher dose to stimulate the declining cell-mediated immunity, the same vaccine has been shown to reduce the incidence and severity of herpes zoster in immunocompetent individuals older than 60 years. Vaccination of immuno-compromised subjects with this VZV vaccine is problematic and various strategies need to be explored. Differences in the pathomechanisms of infection, latency and immune evasion of VZV and HSV, together with host genetic factors, may explain the availability of the successful VZV vaccine and the failures of the past HSV vaccine candidates. PMID:24292083

Sarkadi, Julia

2013-12-01

335

Recombinant vesicular stomatitis virus-based vaccines against Ebola and Marburg virus infections.  

PubMed

The filoviruses, Marburg virus and Ebola virus, cause severe hemorrhagic fever with a high mortality rate in humans and nonhuman primates. Among the most-promising filovirus vaccines under development is a system based on recombinant vesicular stomatitis virus (rVSV) that expresses a single filovirus glycoprotein (GP) in place of the VSV glycoprotein (G). Importantly, a single injection of blended rVSV-based filovirus vaccines was shown to completely protect nonhuman primates against Marburg virus and 3 different species of Ebola virus. These rVSV-based vaccines have also shown utility when administered as a postexposure treatment against filovirus infections, and a rVSV-based Ebola virus vaccine was recently used to treat a potential laboratory exposure. Here, we review the history of rVSV-based vaccines and pivotal animal studies showing their utility in combating Ebola and Marburg virus infections. PMID:21987744

Geisbert, Thomas W; Feldmann, Heinz

2011-11-01

336

A plant-derived edible vaccine against hepatitis B virus  

Microsoft Academic Search

The infectious hepatitis B virus repre- sents 42 nm spherical double-shelled particles. How- ever, analysis of blood from hepatitis B virus carriers revealed the presence of smaller 22 nm particles consisting of a viral envelope surface protein. These particles are highly immunogenic and have been used in the design of hepatitis B virus vaccine produced in yeast. Upon expression in

J. KAPUSTA; A. MODELSKA; M. FIGLEROWICZ; T. PNIEWSKI; M. LETELLIER; O. LISOWA; V. YUSIBOV; H. KOPROWSKI; A. PLUCIENNICZAK; A. B. LEGOCKI

337

Chitosan nanoparticle encapsulated hemagglutinin-split influenza virus mucosal vaccine.  

PubMed

Subunit/split influenza vaccines are less reactogenic compared with the whole virus vaccines. However, their immunogenicity is relatively low and thus required proper adjuvant and/or delivery vehicle for immunogenicity enhancement. Influenza vaccines administered intramuscularly induce minimum, if any, mucosal immunity at the respiratory mucosa which is the prime site of the infection. In this study, chitosan (CS) nanoparticles were prepared by ionic cross-linking of the CS with sodium tripolyphosphate (TPP) at the CS/TPP ratio of 1:0.6 using 2 h mixing time. The CS/TPP nanoparticles were used as delivery vehicle of an intranasal influenza vaccine made of hemagglutinin (HA)-split influenza virus product. Innocuousness, immunogenicity, and protective efficacy of the CS/TPP-HA vaccine were tested in influenza mouse model in comparison with the antigen alone vaccine. The CS/TPP-HA nanoparticles had required characteristics including nano-sizes, positive charges, and high antigen encapsulation efficiency. Mice that received two doses of the CS/TPP-HA vaccine intranasally showed no adverse symptoms indicating the vaccine innocuousness. The animals developed higher systemic and mucosal antibody responses than vaccine made of the HA-split influenza virus alone. The CS/TPP-HA vaccine could induce also a cell-mediated immune response shown as high numbers of IFN-?-secreting cells in spleens while the HA vaccine alone could not. Besides, the CS nanoparticle encapsulated HA-split vaccine reduced markedly the influenza morbidity and also conferred 100% protective rate to the vaccinated mice against lethal influenza virus challenge. Overall results indicated that the CS nanoparticles invented in this study is an effective and safe delivery vehicle/adjuvant for the influenza vaccine. PMID:24343789

Sawaengsak, Chompoonuch; Mori, Yasuko; Yamanishi, Koichi; Mitrevej, Ampol; Sinchaipanid, Nuttanan

2014-04-01

338

Norwalk virus-like particles as vaccines  

PubMed Central

Noroviruses (NoV) cause the great majority of epidemic nonbacterial gastroenteritis in humans. Expression of the capsid protein in recombinant systems, including insect and plant cells, yields assembly of virus-like particles (VLPs) that mimic the antigenic structure of authentic virions, and are relatively acid- and heat-stable. Norwalk virus (NV), the prototype NoV, has been studied extensively, and Norwalk virus-like particles (NVLPs) produced in insect cells and plants are immunogenic in mice and humans when delivered orally, stimulating the production of systemic and mucosal anti-NV antibodies. NVLPs are also highly immunogenic when delivered intranasally, provoking antibodies at levels similar to orally delivered VLP at much lower doses. Oral and nasal delivery of NVLPs efficiently produces antibodies at distal mucosal sites, which suggests that NVLPs could be used to deliver heterologous peptide antigens by production of genetic fusion chimeric capsid proteins. Examination of norovirus VLP surface structures and receptor binding motifs facilitates identification of potential sites for insertion of foreign peptides that will minimally affect the efficiency of VLP assembly and receptor binding. Thus, there is strong potential to use norovirus VLPs as vaccine-delivery vehicles. PMID:20218858

Herbst-Kralovetz, Melissa; Mason, Hugh S; Chen, Qiang

2010-01-01

339

9 CFR 113.200 - General requirements for killed virus vaccines.  

Code of Federal Regulations, 2011 CFR

...false General requirements for killed virus vaccines. 113.200 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.200 General...

2011-01-01

340

9 CFR 113.300 - General requirements for live virus vaccines.  

... false General requirements for live virus vaccines. 113.300 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.300 General...

2014-01-01

341

9 CFR 113.300 - General requirements for live virus vaccines.  

Code of Federal Regulations, 2012 CFR

... false General requirements for live virus vaccines. 113.300 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.300 General...

2012-01-01

342

9 CFR 113.200 - General requirements for killed virus vaccines.  

...false General requirements for killed virus vaccines. 113.200 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.200 General...

2014-01-01

343

9 CFR 113.200 - General requirements for killed virus vaccines.  

Code of Federal Regulations, 2013 CFR

...false General requirements for killed virus vaccines. 113.200 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.200 General...

2013-01-01

344

9 CFR 113.200 - General requirements for killed virus vaccines.  

Code of Federal Regulations, 2012 CFR

...false General requirements for killed virus vaccines. 113.200 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.200 General...

2012-01-01

345

9 CFR 113.300 - General requirements for live virus vaccines.  

Code of Federal Regulations, 2013 CFR

... false General requirements for live virus vaccines. 113.300 Section 113...INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS...VECTORS STANDARD REQUIREMENTS Live Virus Vaccines § 113.300 General...

2013-01-01

346

Coinfection by Vaccinia virus and an Orf virus-like parapoxvirus in an outbreak of vesicular disease in dairy cows in midwestern Brazil.  

PubMed

The current report describes an outbreak of vesicular disease affecting dairy cows in midwestern Brazil in which a coinfection with 2 poxviruses-Vaccinia virus (VACV) and a parapoxvirus-was demonstrated. Milking cows presented vesicles, painful reddish or whitish papules, and scabby proliferative lesions in the teats and udder, in a clinical course of approximately 10-21 days. Histologically, multifocal areas of moderate to severe acanthosis, spongiosis, hypergranulosis, and parakeratotic or orthokeratotic hyperkeratosis with adjacent focally extensive ulcers were observed in the epidermis. Rounded eosinophilic inclusion bodies were observed in the cytoplasm of epithelial cells of areas with acanthosis or necrosis. Moderate inflammatory infiltrate of lymphocytes, plasma cells, neutrophils, and macrophages were observed in some dermal areas. Two people milking the affected cows developed lesions on the hands, painful papules which progressed to ulcerative and scabby lesions in 4-7 days. Electron microscopy of scabs from 1 cow revealed the concomitant presence of orthopoxvirus and parapoxvirus particles. Scabs from 2 cows were positive by polymerase chain reaction for the parapoxvirus B2L gene; 1 of the scabs was also positive for the VACV vgf gene. Nucleotide sequencing of the B2L amplicon revealed a similarity of 96-99% with Orf virus (ORFV) and lower identity with Pseudocowpox virus (92-95%) and Bovine papular stomatitis virus (85-86%). Nucleotide sequencing of a region of parapoxvirus DNA polymerase gene revealed a high similarity (98-100%) with ORFV sequences. Thus, an unusual coinfection with VACV and a parapoxvirus, likely ORFV, was demonstrated in the outbreak. PMID:23404478

de Sant'Ana, Fabiano J F; Leal, Fábio A A; Rabelo, Rogério E; Vulcani, Valcinir A S; Moreira, Carlos A; Cargnelutti, Juliana F; Flores, Eduardo F

2013-03-01

347

Distinct Humoral and Cellular Immunity Induced by Alternating Prime-boost Vaccination Using Plasmid DNA and Live Viral Vector Vaccines Expressing the E Protein of Dengue Virus Type 2  

PubMed Central

Background Dengue virus, which belongs to the Flavivirus genus of the Flaviviridae family, causes fatal dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) with infection risk of 2.5 billion people worldwide. However, approved vaccines are still not available. Here, we explored the immune responses induced by alternating prime-boost vaccination using DNA vaccine, adenovirus, and vaccinia virus expressing E protein of dengue virus type 2 (DenV2). Methods Following immunization with DNA vaccine (pDE), adenovirus (rAd-E), and/or vaccinia virus (VV-E) expressing E protein, E protein-specific IgG and its isotypes were determined by conventional ELISA. Intracellular CD154 and cytokine staining was used for enumerating CD4+ T cells specific for E protein. E protein-specific CD8+ T cell responses were evaluated by in vivo CTL killing activity and intracellular IFN-? staining. Results Among three constructs, VV-E induced the most potent IgG responses, Th1-type cytokine production by stimulated CD4+ T cells, and the CD8+ T cell response. Furthermore, when the three constructs were used for alternating prime-boost vaccination, the results revealed a different pattern of CD4+ and CD8+ T cell responses. i) Priming with VV-E induced higher E-specific IgG level but it was decreased rapidly. ii) Strong CD8+ T cell responses specific for E protein were induced when VV-E was used for the priming step, and such CD8+ T cell responses were significantly boosted with pDE. iii) Priming with rAd-E induced stronger CD4+ T cell responses which subsequently boosted with pDE to a greater extent than VV-E and rAd-E. Conclusion These results indicate that priming with live viral vector vaccines could induce different patterns of E protein- specific CD4+ and CD8+ T cell responses which were significantly enhanced by booster vaccination with the DNA vaccine. Therefore, our observation will provide valuable information for the establishment of optimal prime-boost vaccination against DenV. PMID:22194710

George, Junu A.

2011-01-01

348

Antibody response of five bird species after vaccination with a killed West Nile virus vaccine.  

PubMed

West Nile virus has been associated with numerous bird mortalities in the United States since 1999. Five avian species at three zoological parks were selected to assess the antibody response to vaccination for West Nile virus: black-footed penguins (Spheniscus demersus), little blue penguins (Eudyptula minor), American flamingos (Phoenicopterus ruber), Chilean flamingos (Phoenicopterus chilensis), and Attwater's prairie chickens (Tympanuchus cupido attwateri). All birds were vaccinated intramuscularly at least twice with a commercially available inactivated whole virus vaccine (Innovator). Significant differences in antibody titer over time were detected for black-footed penguins and both flamingo species. PMID:17679507

Okeson, Danelle M; Llizo, Shirley Yeo; Miller, Christine L; Glaser, Amy L

2007-06-01

349

The Vaccinia Virus Bifunctional Gene J3 (Nucleoside2?- O-)-methyltransferase and Poly(A) Polymerase Stimulatory Factor Is Implicated as a Positive Transcription Elongation Factor by Two Genetic Approaches  

Microsoft Academic Search

Vaccinia virus genes A18 and G2 affect the elongation and termination of postreplicative viral gene transcription in opposite ways. Viruses with mutations in gene A18 produce abnormally long transcripts, indicating that A18 is a negative transcription elongation factor. Viruses containing mutations in gene G2 produce transcripts that are abnormally short, truncated specifically from their 3? ends, indicating that G2 is

Donald R. Latner; Ying Xiang; Jackie I. Lewis; Jeremy Condit; Richard C. Condit

2000-01-01

350

Ebola virus vaccines: an overview of current approaches.  

PubMed

Ebola hemorrhagic fever is one of the most fatal viral diseases worldwide affecting humans and nonhuman primates. Although infections only occur frequently in Central Africa, the virus has the potential to spread globally and is classified as a category A pathogen that could be misused as a bioterrorism agent. As of today there is no vaccine or treatment licensed to counteract Ebola virus infections. DNA, subunit and several viral vector approaches, replicating and non-replicating, have been tested as potential vaccine platforms and their protective efficacy has been evaluated in nonhuman primate models for Ebola virus infections, which closely resemble disease progression in humans. Though these vaccine platforms seem to confer protection through different mechanisms, several of them are efficacious against lethal disease in nonhuman primates attesting that vaccination against Ebola virus infections is feasible. PMID:24575870

Marzi, Andrea; Feldmann, Heinz

2014-04-01

351

Comparison of the safety and immunogenicity of ACAM1000, ACAM2000 and Dryvax in healthy vaccinia-naive adults.  

PubMed

Currently, more than half of the world's population has no immunity against smallpox variola major virus. This phase I double-blind, randomized trial was conducted to compare the safety and immunogenicity of two clonally derived, cell-culture manufactured vaccinia strains, ACAM1000 and ACAM2000, to the parent vaccine, Dryvax. Thirty vaccinia-naďve subjects were enrolled into each of three groups and vaccines were administered percutaneously using a bifurcated needle at a dose of 1.0x10(8)PFU/mL. All subjects had a primary skin reaction indicating a successful vaccination. The adverse events, 4-fold neutralizing antibody rise and T cell immune responses were similar between the groups. PMID:19071184

Frey, Sharon E; Newman, Frances K; Kennedy, Jeffrey S; Ennis, Francis; Abate, Getahun; Hoft, Daniel F; Monath, Thomas P

2009-03-01

352

Chimpanzee adenovirus vaccine protects against Zaire Ebola virus  

Microsoft Academic Search

This study evaluated the use of a chimpanzee-based adenovirus vaccine in mouse and Guinea pigs models of Zaire Ebola virus (ZEBOV) infection. Vaccine vector expressing the envelope glycoprotein of ZEBOV was created from the molecular clone of chimpanzee adenovirus pan7 (AdC7). AdC7 vaccine stimulated robust T and B cell responses to ZEBOV in naďve mice inducing complete protection to an

Gary P. Kobinger; Heinz Feldmann; Yan Zhi; Gregory Schumer; Guangping Gao; Friederike Feldmann; Steven Jones; James M. Wilson

2006-01-01

353

Interaction between live avian pneumovirus and Newcastle disease virus vaccines in specific pathogen free chickens  

Microsoft Academic Search

One-day-old specific pathogen free White Leghorn chicks were vaccinated with live avian pneumovirus (APV) vaccine, live Newcastle disease virus (NDV) vaccine or both. At intervals up to 28 days after vaccination, distribution of the virus in the tissues was studied, together with humoral and mucosal antibody responses in lachrymal fluid and tracheal washes. APV vaccine was detected for almost twice

K. Ganapathy; P. Cargill; E. Montiel; R. C. Jones

2005-01-01

354

Influenza Virus-Like Particles as Pandemic Vaccines  

Microsoft Academic Search

\\u000a There is an urgent need to develop novel approaches for vaccination against emerging pathogenic avian influenza viruses as\\u000a a priority for pandemic preparedness. Influenza virus-like particles (VLPs) have been suggested and developed as a new generation\\u000a of non-egg-based cell culture-derived vaccine candidates against influenza infection. Influenza VLPs are formed by a self-assembly\\u000a process incorporating structural proteins into budding particles composed

S. M. Kang; P. Pushko; R. A. Bright; G. Smith; R. W. Compans

355

Adherence to hepatitis B virus vaccination at syringe exchange sites  

Microsoft Academic Search

Injection drug users (IDUs) are at high risk for hepatitis B virus (HBV); however, they often do not receive preventive vaccination.\\u000a ‘IDUs who use mobile health care services linked to a syring exchange program in New Haven were routinely screened for HBV,\\u000a hepatitis C virus, and syphilis. Individuals without prior exposure to HBV were offered three-part vaccination series. Of\\u000a the

Frederick L. Altice; Robert D. Bruce; Mary R. Walton; Marta I. Buitrago

2005-01-01

356

Evaluation in Nonhuman Primates of Vaccines against Ebola Virus  

Microsoft Academic Search

Ebola virus (EBOV) causes acute hemorrhagic fever that is fatal in up to 90% of cases in both humans and nonhuman primates. No vaccines or treatments are available for human use. We evaluated the effects in nonhuman primates of vaccine strategies that had protected mice or guinea pigs from lethal EBOV infec- tion. The following immunogens were used: RNA replicon

Thomas W. Geisbert; Peter Pushko; Kevin Anderson; Jonathan Smith; Kelly J. Davis; Peter B. Jahrling

2002-01-01

357

Otitis media: viruses, bacteria, biofilms and vaccines.  

PubMed

Otitis media typically presents as either acute otitis media (AOM), with symptoms including fever, otalgia, otorrhoea or irritability and short duration; or as otitis media with effusion (OME), which is often asymptomatic and characterised by accumulation of fluid in the middle ear. Diagnostic certainty of otitis media is challenging, given the young age of patients and variability of symptoms. Otitis media predominantly occurs as coincident to viral upper respiratory tract infections and/or bacterial infections. Common viruses that cause upper respiratory tract infection are frequently associated with AOM and new-onset OME. These include respiratory syncytial virus, rhinovirus, adenovirus, parainfluenza and coronavirus. Predominant bacteria that cause otitis media are Streptococcus pneumoniae, Moraxella catarrhalis, and non-typeable Haemophilus influenzae. Antibiotic therapy does not significantly benefit most patients with AOM, but long-term prophylactic antibiotic therapy can reduce the risk of otitis media recurrence among children at high risk. In Australia, 84% of AOM is treated with antibiotic therapy, which contributes to development of antibiotic resistance. Vaccine development is a key future direction for reducing the world burden of otitis media, but requires polymicrobial formulation and ongoing monitoring and modification to ensure sustained reduction in disease burden. PMID:19883356

Massa, Helen M; Cripps, Allan W; Lehmann, Deborah

2009-11-01

358

The Orf virus E3L homologue is able to complement deletion of the vaccinia virus E3L gene in vitro but not in vivo.  

PubMed

Orf virus (OV), the prototypic parapoxvirus, is resistant to the effects of interferon (IFN) and this function of OV has been mapped to the OV20.0L gene. The protein product of this gene shares 31% amino acid identity to the E3L-encoded protein of vaccinia virus (VV) that is required for the broad host range and IFN-resistant phenotype of VV in cells in culture and for virulence of the virus in vivo. In this study we investigated whether the distantly related OV E3L homologue could complement the deletion of E3L in VV. The recombinant VV (VV/ORF-E3L) expressing the OV E3L homologue in place of VV E3L was indistinguishable from wt VV in its cell-culture phenotype. But VV/ORF-E3L was over a 1000-fold less pathogenic than wt VV (LD(50) > 5 x 10(6) PFU, compared to LD(50) of wtVV = 4 x 10(3) PFU) following intranasal infection of mice. While wt VV spread to the lungs and brain and replicated to high titers in the brain of infected mice, VV/ORF-E3L could not be detected in the lungs or brain following intranasal infection. VV/ORF-E3L was at least 100,000-fold less pathogenic than wt VV on intracranial injection. Domain swap experiments demonstrate that the difference in pathogenesis maps to the C-terminal domain of these proteins. This domain has been shown to be required for the dsRNA binding function of the VV E3L. PMID:14517083

Vijaysri, Sangeetha; Talasela, Latha; Mercer, Andrew A; Mcinnes, Colin J; Jacobs, Bertram L; Langland, Jeffrey O

2003-09-15

359

[Limbic encephalitis caused by herpes simplex virus infection after vaccination against the influenza virus].  

PubMed

Various causative factors, including viral infection, autoimmunity, and paraneoplasia, are considered to be involved in the pathomechanism of limbic encephalitis. We encountered a patient who developed limbic encephalitis after vaccination against the influenza virus. In Japan, an influenza epidemic occurs every winter, and vaccination against the influenza virus is recommended. However, there have been reports of serious side effects such as the development of Guillain-Barré syndrome and acute disseminated encephalomyelitis after influenza vaccination; these findings indicate the activation of an autoimmune pathomechanism after vaccination. Here, we discuss the relationship between limbic encephalitis and influenza vaccination from the perspective of viral infection and autoimmunity. We considered that limbic encephalitis was caused by the herpes simplex virus, and hypothesized that this clinical condition rarely develops as a sole consequence of influenza vaccination but rather develops because of the activation of an autoimmune pathomechanism after vaccination. PMID:20548122

Utumi, Yushi; Iseki, Eizo; Murayama, Norio; Ichimiya, Yosuke; Arai, Heii

2010-06-01

360

Safety of West Nile Virus vaccines in sandhill crane chicks  

USGS Publications Warehouse

West Nile virus arrived in North America in 1999 and has spread across the continent in the ensuing years. The virus has proven deadly to a variety of native avian species including sandhill cranes (Grus canadensis). In order to provide safe and efficacious protection for captive and released populations of whooping cranes (G. americana), we have conducted a series of four research projects. The last of these was a study of the effects of two different West Nile virus vaccines on young Florida sandhill crane (G. c. pratensis) chicks and subsequent challenge with the virus. We found that vaccinating crane chicks as early as day 7 post-hatch caused no adverse reactions or noticeable morbidity. We tested both a commercial equine vaccine West Nile - Innovator (Fort Dodge Laboratories, Fort Dodge, Iowa) and a new recombinant DNA vaccine (Centers for Disease Control). We had a 33% mortality in control chicks (n =6) from West Nile virus infection, versus 0% mortality in two groups of vaccinated chicks (n = 12), indicating the two vaccines tested were not only safe but effective in preventing West Nile virus.

Olsen, G.H.; Miller, K.J.; Docherty, D.E.; Bochsler, V.S.

2008-01-01

361

Preferential colonization of metastases by oncolytic vaccinia virus strain GLV-1h68 in a human PC-3 prostate cancer model in nude mice.  

PubMed

Recently, we showed that the oncolytic vaccinia virus GLV-1h68 has a significant therapeutic potential in treating lymph node metastases of human PC-3 prostate carcinoma in tumor xenografts. In this study, underlying mechanisms of the virus-mediated metastases reduction were analyzed. Immunohistochemistry demonstrated that virus-treatment resulted in a drastically decrease of blood and lymph vessels, representing essential routes for PC-3 cell migration, in both tumors and metastases. Thus, GLV-1h68 drastically reduced essential routes for the metastatic spread of PC-3 cells. Furthermore, analysis of viral distribution in GLV-1h68-injected tumor-bearing mice by plaque assays, revealed significantly higher virus titers in metastases compared to solid tumors. To elucidate conditions potentially mediating the preferential viral colonization and eradication of metastases, microenvironmental components of uninfected tumors and metastases were compared by microscopic studies. These analyses revealed that PC-3 lymph node metastases showed increased vascular permeability, higher proliferation status of tumor cells as determined by BrdU- and Ki-67 assays and lesser necrosis of PC-3 cells than solid tumors. Moreover, an increased number of immune cells (MHCII(+)/CD68(+) macrophages, MHCII(+)/CD19(+) B lymphocytes) combined with an up-regulated expression of pro-inflammatory cytokines was observed in metastases in comparison to primary PC-3 tumors. We propose that these microenvironmental components mediated the metastatic tropism of GLV-1h68. Therefore, vaccinia virus-based oncolytic virotherapy might offer a novel treatment of metastatic prostate carcinomas in humans. PMID:23049897

Donat, Ulrike; Weibel, Stephanie; Hess, Michael; Stritzker, Jochen; Härtl, Barbara; Sturm, Julia B; Chen, Nanhai G; Gentschev, Ivaylo; Szalay, Aladar A

2012-01-01

362

Preferential Colonization of Metastases by Oncolytic Vaccinia Virus Strain GLV-1h68 in a Human PC-3 Prostate Cancer Model in Nude Mice  

PubMed Central

Recently, we showed that the oncolytic vaccinia virus GLV-1h68 has a significant therapeutic potential in treating lymph node metastases of human PC-3 prostate carcinoma in tumor xenografts. In this study, underlying mechanisms of the virus-mediated metastases reduction were analyzed. Immunohistochemistry demonstrated that virus-treatment resulted in a drastically decrease of blood and lymph vessels, representing essential routes for PC-3 cell migration, in both tumors and metastases. Thus, GLV-1h68 drastically reduced essential routes for the metastatic spread of PC-3 cells. Furthermore, analysis of viral distribution in GLV-1h68-injected tumor-bearing mice by plaque assays, revealed significantly higher virus titers in metastases compared to solid tumors. To elucidate conditions potentially mediating the preferential viral colonization and eradication of metastases, microenvironmental components of uninfected tumors and metastases were compared by microscopic studies. These analyses revealed that PC-3 lymph node metastases showed increased vascular permeability, higher proliferation status of tumor cells as determined by BrdU- and Ki-67 assays and lesser necrosis of PC-3 cells than solid tumors. Moreover, an increased number of immune cells (MHCII+/CD68+ macrophages, MHCII+/CD19+ B lymphocytes) combined with an up-regulated expression of pro-inflammatory cytokines was observed in metastases in comparison to primary PC-3 tumors. We propose that these microenvironmental components mediated the metastatic tropism of GLV-1h68. Therefore, vaccinia virus-based oncolytic virotherapy might offer a novel treatment of metastatic prostate carcinomas in humans. PMID:23049897

Donat, Ulrike; Weibel, Stephanie; Hess, Michael; Stritzker, Jochen; Hartl, Barbara; Sturm, Julia B.; Chen, Nanhai G.; Gentschev, Ivaylo; Szalay, Aladar A.

2012-01-01

363

[Recombinant viruses of poultry as vector vaccines against fowl plague].  

PubMed

To help in the control of fowl plague caused by highly pathogenic avian influenza A viruses of hemagglutinin (HA) subtypes H5 and H7 several vaccines have been developed. A prophylactic immunization of poultry with inactivated influenza viruses in non-endemic situations is questionable, however, due to the impairment of serological identification of field virus-infected animals which hinders elimination of the infectious agent from the population. This problem might be overcome by the use of genetically engineered marker vaccines which contain only the protective influenza virus hemagglutinin. Infected animals could then be unambiguously identified by their serum antibodies against other influenza virus proteins, e.g. neuraminidase or nucleoprotein. For such a use, purified HA or HA-expressing DNA vaccines are conceivable. Economically advantageous and easier to apply are modified live virus vaccines in use against other poultry diseases, which have been modified to express influenza virus HA. So far, recombinant HA-expressing fowlpox virus (FPV) as well as infectious laryngotracheitis and Newcastle disease viruses have been asssessed in animal experiments. An H5-expressing FPV recombinant is already in use in Central America and Southeast Asia but without accompanying marker diagnostics. Advantages and disadvantages of the different viral vectors are discussed. PMID:16573206

Fuchs, Walter; Veits, Jutta; Mettenleiter, Thomas C

2006-01-01

364

Effects of Nasal or Pulmonary Delivered Treatments with an Adenovirus Vectored Interferon (mDEF201) on Respiratory and Systemic Infections in Mice Caused by Cowpox and Vaccinia Viruses  

PubMed Central

An adenovirus 5 vector encoding for mouse interferon alpha, subtype 5 (mDEF201) was evaluated for efficacy against lethal cowpox (Brighton strain) and vaccinia (WR strain) virus respiratory and systemic infections in mice. Two routes of mDEF201 administration were used, nasal sinus (5-µl) and pulmonary (50-µl), to compare differences in efficacy, since the preferred treatment of humans would be in a relatively small volume delivered intranasally. Lower respiratory infections (LRI), upper respiratory infections (URI), and systemic infections were induced by 50-µl intranasal, 10-µl intranasal, and 100-µl intraperitoneal virus challenges, respectively. mDEF201 treatments were given prophylactically either 24 h (short term) or 56d (long-term) prior to virus challenge. Single nasal sinus treatments of 106 and 107 PFU/mouse of mDEF201 protected all mice from vaccinia-induced LRI mortality (comparable to published studies with pulmonary delivered mDEF201). Systemic vaccinia infections responded significantly better to nasal sinus delivered mDEF201 than to pulmonary treatments. Cowpox LRI infections responded to 107 mDEF201 treatments, but a 106 dose was only weakly protective. Cowpox URI infections were equally treatable by nasal sinus and pulmonary delivered mDEF201 at 107 PFU/mouse. Dose-responsive prophylaxis with mDEF201, given one time only 56 d prior to initiating a vaccinia virus LRI infection, was 100% protective from 105 to 107 PFU/mouse. Improvements in lung hemorrhage score and lung weight were evident, as were decreases in liver, lung, and spleen virus titers. Thus, mDEF201 was able to treat different vaccinia and cowpox virus infections using both nasal sinus and pulmonary treatment regimens, supporting its development for humans. PMID:23874722

Smee, Donald F.; Wong, Min-Hui; Hurst, Brett L.; Ennis, Jane; Turner, Jeffrey D.

2013-01-01

365

Biogenesis of Vaccinia: Analysis by Three-Factor Crosses Reveals Mutual Influence on Stability of Drug Resistance and Temperature Sensitivity when Both Markers Occur in Some Recombinant Virus Isolates  

Microsoft Academic Search

Summary Recombination analysis with 5 temperature-sensitive (ts) mutants of vaccinia virus, relegated to the E category phenotype and mimicking closely the effects produced by the antibiotic rifampicin, was undertaken to determine whether the genetic loci determining this phenotype were clustered on the genetic map. Optimum conditions for analysis were established with respect to the MOI and duration of incubation. At

Karim Essani; Samuel Dales

1983-01-01

366

Protection induced by infectious laryngotracheitis virus vaccines alone and combined with Newcastle disease virus and/or infectious bronchitis virus vaccines.  

PubMed

Two types of live attenuated vaccines have been used worldwide for the control of infectious laryngotracheitis virus (ILTV): 1) chicken embryo origin (CEO) vaccines; and 2) tissue culture origin vaccines (TCO). However, the disease persists in spite of extensive use of vaccination, particularly in areas of intense broiler production. Among the factors that may influence the efficiency of ILTV live attenuated vaccines is a possible interference of Newcastle Disease virus (NDV) and infectious bronchitis virus (IBV) vaccines with the protection induced by ILTV vaccines. The protection induced by CEO and TCO vaccines was evaluated when administered at 14 days of age alone or in combination with the B1 type strain of NDV (B1) and/or the Arkansas (ARK) and Massachusetts (MASS) serotypes of IBV vaccines. Two weeks after vaccination (28 days of age), the chickens were challenged with a virulent ILTV field strain (63140 isolate, group V genotype). Protection was evaluated at 5 and 7 days postchallenge by scoring clinical signs and quantifying the challenge virus load in the trachea using real-time PCR (qPCR). In addition, the viral load of the vaccine viruses (ILTV, NDV, and IBV) was quantified 3 and 5 days postvaccination also using qPCR. The results of this study indicate that the NDV (B1) and IBV (ARK) vaccines and a multivalent vaccine constituted by NDV (B1) and IBV (ARK and MASS) did not interfere with the protection induced by the CEO ILTV vaccine. However, the NDV (BI) and the multivalent (B1/MASS/ARK) vaccines interfered with the protection induced by the TCO vaccine (P < 0.05). Either in combination or by themselves, the NDV and IBV vaccines decreased the tracheal replication of the TCO vaccine and the protection induced by this vaccine, since the ILTV-vaccinated and -challenged chickens displayed significantly more severe clinical signs and ILTV load (P < 0.05) than chickens vaccinated with the TCO vaccine alone. Although NDV and IBV challenges were not performed, the antibody responses elicited by NDV and/or the IBV vaccinations were significantly reduced (P < 0.05) when applied in combination with the CEO vaccine. PMID:21313841

Vagnozzi, Ariel; García, Maricarmen; Riblet, Sylva M; Zavala, Guillermo

2010-12-01

367

Challenges and recent advancements in infectious laryngotracheitis virus vaccines.  

PubMed

Over the past 80 years, biosecurity measures and vaccines have been used to prevent the occurrence of outbreaks of infectious laryngotracheitis (ILT). Despite these control strategies, ILT continues to have an impact on intensive poultry industries. Attenuated vaccines, particularly those derived by passage in chicken embryos, have been associated with a number of side effects, including residual virulence, transmission to naďve birds, establishment of latent infections with subsequent reactivation and shedding of virus, and reversion to virulence after in vivo passage. Most recently, recombination between attenuated ILT vaccines in the field has been shown to be responsible for the emergence of new virulent viruses that have caused widespread disease. To address some of these issues, new-generation virally vectored recombinant vaccines have been developed and recently released in some countries. In addition, recombinant deletion mutants of ILT virus have been proposed as vaccine candidates. In this review, recent advances in the understanding of the epidemiology of traditionally attenuated ILT vaccines as well as in the development and use of new generation vaccines are examined. Next-generation vaccines, along with more appropriate immunological screening strategies, are identified as particularly promising options to enhance ILT control in the future. PMID:23718807

Coppo, Mauricio J C; Noormohammadi, Amir H; Browning, Glenn F; Devlin, Joanne M

2013-01-01

368

Antibody landscapes after influenza virus infection or vaccination.  

PubMed

We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals. PMID:25414313

Fonville, J M; Wilks, S H; James, S L; Fox, A; Ventresca, M; Aban, M; Xue, L; Jones, T C; Le, N M H; Pham, Q T; Tran, N D; Wong, Y; Mosterin, A; Katzelnick, L C; Labonte, D; Le, T T; van der Net, G; Skepner, E; Russell, C A; Kaplan, T D; Rimmelzwaan, G F; Masurel, N; de Jong, J C; Palache, A; Beyer, W E P; Le, Q M; Nguyen, T H; Wertheim, H F L; Hurt, A C; Osterhaus, A D M E; Barr, I G; Fouchier, R A M; Horby, P W; Smith, D J

2014-11-21

369

Comparison of individual and combination DNA vaccines for B. anthracis, Ebola virus, Marburg virus and Venezuelan equine encephalitis virus  

Microsoft Academic Search

Multiagent DNA vaccines for highly pathogenic organisms offer an attractive approach for preventing naturally occurring or deliberately introduced diseases. Few animal studies have compared the feasibility of combining unrelated gene vaccines. Here, we demonstrate that DNA vaccines to four dissimilar pathogens that are known biowarfare agents, Bacillus anthracis, Ebola (EBOV), Marburg (MARV), and Venezuelan equine encephalitis virus (VEEV), can elicit

Jenny Riemenschneider; Aura Garrison; Joan Geisbert; Peter Jahrling; Michael Hevey; Diane Negley; Alan Schmaljohn; John Lee; Mary Kate Hart; Lorna Vanderzanden; David Custer; Mike Bray; Albert Ruff; Bruce Ivins; Anthony Bassett; Cynthia Rossi; Connie Schmaljohn

2003-01-01

370

Neurovirulence of varicella and the live attenuated varicella vaccine virus  

PubMed Central

Varicella-zoster virus (VZV) is a neurotropic herpesvirus, which can cause a variety of complications during varicella infections. These range from meningoencephalitis to polyneuritis to retinitis. After primary VZV infection, VZV enters the dorsal root ganglia in a latent state. Reactivation from latency leads to zoster. Zoster ophthalmicus in particular can in turn lead to involvement of the cerebral arteries and subsequent stroke. The velocity of VZV is 13 cm per day, as virus travels from ganglion to skin. The live attenuated varicella vaccine virus is markedly less neurovirulent than the wild type virus. Nevertheless, a few cases of herpes zoster due to the vaccine virus have been documented. Usually, herpes zoster occurs in the same arm as the vaccination, often 3 or more years after vaccination. Thus, herpes zoster in a vaccinee often represents a reactivation of vaccine virus that was carried to the cervical dorsal root ganglia from a site of local replication in the arm. Finally, the role of autophagy during VZV is discussed. Autophagosome formation is a prominent feature in the skin vesicles during both varicella and herpes zoster. Therefore, autophagy is one of the innate immune mechanisms associated with VZV infection in humans. PMID:22889542

Horien, Corey; Grose, Charles

2012-01-01

371

Recent progress in West Nile virus diagnosis and vaccination  

PubMed Central

West Nile virus (WNV) is a positive-stranded RNA virus belonging to the Flaviviridae family, a large family with 3 main genera (flavivirus, hepacivirus and pestivirus). Among these viruses, there are several globally relevant human pathogens including the mosquito-borne dengue virus (DENV), yellow fever virus (YFV), Japanese encephalitis virus (JEV) and West Nile virus (WNV), as well as tick-borne viruses such as tick-borne encephalitis virus (TBEV). Since the mid-1990s, outbreaks of WN fever and encephalitis have occurred throughout the world and WNV is now endemic in Africa, Asia, Australia, the Middle East, Europe and the Unites States. This review describes the molecular virology, epidemiology, pathogenesis, and highlights recent progress regarding diagnosis and vaccination against WNV infections. PMID:22380523

2012-01-01

372

Influenza virus surveillance, vaccine strain selection, and manufacture.  

PubMed

As outlined in other chapters, the influenza virus, existing laboratory diagnostic abilities, and disease epidemiology have several peculiarities that impact on the timing and processes for the annual production of influenza vaccines. The chapter provides an overview on the key biological and other factors that influence vaccine production. They are the reason for an "annual circle race" beginning with global influenza surveillance during the influenza season in a given year to the eventual supply of vaccines 12 months later in time before the next seasonal outbreak and so on. As influenza vaccines are needed for the Northern and Southern Hemisphere outbreaks in fall and spring, respectively, global surveillance and vaccine production has become a year round business. Its highlights are the WHO recommendations on vaccine strains in February and September and the eventual delivery of vaccine doses in time before the coming influenza season. In between continues vaccine strain and epidemiological surveillance, preparation of new high growth reassortments, vaccine seed strain preparation and development of standardizing reagents, vaccine bulk production, fill-finishing and vaccine release, and in some regions, clinical trials for regulatory approval. PMID:22528158

Stöhr, Klaus; Bucher, Doris; Colgate, Tony; Wood, John

2012-01-01

373

Hepatitis C Virus Vaccines Among People Who Inject Drugs  

PubMed Central

Most people who inject drugs (PWID) are infected with hepatitis C virus (HCV), and PWID have the highest risk of HCV infection of any risk group. The incidence of HCV infection is 5%–25% per year, demonstrating continued need for HCV infection prevention in PWID. Existing data in chimpanzees and PWID suggest that protective immunity against persistent HCV infection is achievable. Due to the high incidence of infection, PWID are both the most likely to benefit from a vaccine and a population in which vaccine efficacy could be tested. Challenges to testing a vaccine in PWID are significant. However, the first HCV vaccine trial in at-risk HCV-uninfected PWID was initiated in 2012. The results will likely guide future vaccine development and strategies for vaccination of this and other high-risk populations. PMID:23884065

Cox, Andrea L.; Thomas, David L.

2013-01-01

374

Anaphylaxis from the Influenza Virus Vaccine  

Microsoft Academic Search

Background: Allergic reactions to the influenza vaccine are uncommon and usually associated with sensitivity to egg or gelatin. The aim of this study was to report the case of anaphylaxis to the influenza vaccine. Methods: Allergy percutaneous skin testing, serum specific IgE testing and IgE immunoblotting were performed to the influenza vaccine, egg, and gelatin. Results: Percutaneous skin testing to

Christopher A. Coop; Synya K. Balanon; Kevin M. White; Bonnie A. Whisman; Melinda M. Rathkopf

2008-01-01

375

Clinical and immunologic responses to multiple doses of IMVAMUNE (Modified Vaccinia Ankara) followed by Dryvax challenge.  

PubMed

Smallpox vaccination with replication deficient vaccinia strains such as Modified Vaccinia Ankara (MVA) may induce protective immunity with improved safety and tolerability profiles compared with currently available smallpox vaccines. Ninety subjects were randomized equally to six groups in a partially blinded, randomized, controlled clinical trial. IMVAMUNE (MVA-BN, Bavarian Nordic A/S, Kvistgĺrd, Denmark) vaccine or placebo was administered at Study Days 0 and 28 by subcutaneous or intramuscular injection and five groups were challenged with Dryvax at study Day 112. Vaccination with two doses of IMVAMUNE was safe and well tolerated compared to Dryvax. IMVAMUNE produced comparable cellular and humoral immune responses to one dose of Dryvax and the immunity induced appears robust 90 days post-vaccination by evidence of attenuated primary cutaneous reaction responses following Dryvax. IMVAMUNE vaccination prior to Dryvax reduced virus replication at the Dryvax site, decreased the size of the primary cutaneous lesion, and decreased the time to healing but did not completely ameliorate the immune response. PMID:18036708

Frey, Sharon E; Newman, Frances K; Kennedy, Jeffrey S; Sobek, Vera; Ennis, Francis A; Hill, Heather; Yan, Lihan K; Chaplin, Paul; Vollmar, Jens; Chaitman, Bernard R; Belshe, Robert B

2007-12-12

376

A complex of seven vaccinia virus proteins conserved in all chordopoxviruses is required for the association of membranes and viroplasm to form immature virions  

SciTech Connect

Early events in vaccinia virus (VAC) morphogenesis, particularly the formation of viral membranes and their association with viroplasm, are poorly understood. Recently, we showed that repression of A30 or G7 expression results in the accumulation of normal viral membranes that form empty-looking immature virions (IV), which are separated from large masses of electron-dense viroplasm. In addition, A30 and G7 physically and functionally interact with each other and with the F10 protein kinase. To identify other proteins involved in early morphogenesis, proteins from cells that had been infected with vaccinia virus expressing an epitope-tagged copy of F10 were purified by immunoaffinity chromatography and analyzed by gel electrophoresis. In addition to F10, A30, and G7, viral proteins A15, D2, D3, and J1 were identified by mass spectrometry of tryptic peptides. Further evidence for the complex was obtained by immunopurification of proteins associated with epitope-tagged A15, D2, and D3. The previously unstudied A15, like other proteins in the complex, was expressed late in infection, associated with virus cores, and required for the stability and kinase activity of F10. Biochemical and electron microscopic analyses indicated that mutants in which A15 or D2 expression was regulated by the Escherichia coli lac operator system exhibited phenotypes characterized by the presence of large numbers of empty immature virions, similar to the results obtained with inducible A30 and G7 mutants. Empty immature virions were also seen by electron microscopy of cells infected with temperature-sensitive mutants of D2 or D3, though the numbers of membrane forms were reduced perhaps due to additional effects of high temperature.

Szajner, Patricia [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Jaffe, Howard [Protein/Peptide Sequence Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892 (United States); Weisberg, Andrea S. [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States); Moss, Bernard [Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 (United States)]. E-mail: bmoss@nih.gov

2004-12-20

377

Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.  

PubMed

To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV. PMID:21562115

Thiele, Sonja; Borschewski, Aljona; Küchler, Judit; Bieberbach, Marc; Voigt, Sebastian; Ehlers, Bernhard

2011-07-01

378

Requirements of New Vaccines against Novel Influenza Viruses  

PubMed Central

The currently available influenza vaccines were developed in the 1930s through the 1960s using technologies that were state-of-the art for the times. Decades of advancement in virology and immunology have provided the tools for making better vaccines against influenza virus. Among young children, live attenuated vaccine had significantly better efficacy than inactivated vaccine. An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing. Otherwise, MF59 adjuvanted influenza vaccine, ATIV was well tolerated in healthy young children and elderly after each of 3 doses and induced greater, longer-lasting, and broader immune responses than a nonadjuvanted trivalent inactivated influenza vaccine, TIV. The enhanced immunogenicity of the adjuvanted vaccine was most evident in very young children and for the B vaccine strain. In case of AS03 ATIV, the safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza. A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail. In conclusion, current improved influenza vaccines are; in the problem target groups are children aged 6–24 months and people over 65 years old of age. Only ATIV has shown significantly greater efficacy than TIV, and its safe.

2014-01-01

379

Chimpanzee adenovirus vaccine protects against Zaire Ebola virus.  

PubMed

This study evaluated the use of a chimpanzee-based adenovirus vaccine in mouse and Guinea pigs models of Zaire Ebola virus (ZEBOV) infection. Vaccine vector expressing the envelope glycoprotein of ZEBOV was created from the molecular clone of chimpanzee adenovirus pan7 (AdC7). AdC7 vaccine stimulated robust T and B cell responses to ZEBOV in naďve mice inducing complete protection to an otherwise lethal challenge of ZEBOV. Complete protection to Zaire Ebola virus was also observed in Guinea pigs vaccinated with a relatively low dose of AdC7 (5 x 10(9)/kg). Pre-existing immunity to AdHu5 was generated in mice following pre-exposure to AdHu5 or administration of pooled human immune globulin. Pre-existing immunity to human adenoviruses severely compromised the efficacy of the human AdHu5 vaccine but not the chimpanzee AdC7 vaccine. These results validate further development of Chimpanzee-based vaccine and highlight the impact of pre-existing immunity to the vaccine carrier. PMID:16356525

Kobinger, Gary P; Feldmann, Heinz; Zhi, Yan; Schumer, Gregory; Gao, Guangping; Feldmann, Friederike; Jones, Steven; Wilson, James M

2006-03-15

380

Formulation of Microneedles Coated with Influenza Virus-like Particle Vaccine  

Microsoft Academic Search

Mortality due to seasonal and pandemic influenza could be reduced by increasing the speed of influenza vaccine production\\u000a and distribution. We propose that vaccination can be expedited by (1) immunizing with influenza virus-like particle (VLP)\\u000a vaccines, which are simpler and faster to manufacture than conventional egg-based inactivated virus vaccines, and (2) administering\\u000a vaccines using microneedle patches, which should simplify vaccine

Yeu-Chun Kim; Fu-Shi Quan; Richard W. Compans; Sang-Moo Kang; Mark R. Prausnitz

2010-01-01

381

Return of inactivated whole-virus vaccine for superior efficacy.  

PubMed

The swine, influenza, H1N1 outbreak in 2009 highlighted the inadequacy of the currently used antibody-based vaccine strategies as a preventive measure for combating influenza pandemics. The ultimate goal for successful control of newly arising influenza outbreaks is to design a single-shot vaccine that will provide long-lasting immunity against all strains of influenza A virus. A large amount of data from animal studies has indicated that the cross-reactive cytotoxic T (Tc) cell response against conserved influenza virus epitopes may be the key immune response needed for a universal influenza vaccine. However, decades of research have shown that the development of safe T-cell-based vaccines for influenza is not an easy task. Here, I discuss the overlooked but potentially highly advantageous inactivation method, namely, ?-ray irradiation, as a mean to reach the Holy Grail of influenza vaccinology. PMID:21844883

Furuya, Yoichi

2012-07-01

382

Attenuated vaccines can recombine to form virulent field viruses.  

PubMed

Recombination between herpesviruses has been seen in vitro and in vivo under experimental conditions. This has raised safety concerns about using attenuated herpesvirus vaccines in human and veterinary medicine and adds to other known concerns associated with their use, including reversion to virulence and disease arising from recurrent reactivation of lifelong chronic infection. We used high-throughput sequencing to investigate relationships between emergent field strains and vaccine strains of infectious laryngotracheitis virus (ILTV, gallid herpesvirus 1). We show that independent recombination events between distinct attenuated vaccine strains resulted in virulent recombinant viruses that became the dominant strains responsible for widespread disease in Australian commercial poultry flocks. These findings highlight the risks of using multiple different attenuated herpesvirus vaccines, or vectors, in the same populations. PMID:22798607

Lee, Sang-Won; Markham, Philip F; Coppo, Mauricio J C; Legione, Alistair R; Markham, John F; Noormohammadi, Amir H; Browning, Glenn F; Ficorilli, Nino; Hartley, Carol A; Devlin, Joanne M

2012-07-13

383

Protection and Virus Shedding of Falcons Vaccinated against Highly Pathogenic Avian Influenza A Virus (H5N1)  

PubMed Central

Because fatal infections with highly pathogenic avian influenza A (HPAI) virus subtype H5N1 have been reported in birds of prey, we sought to determine detailed information about the birds’ susceptibility and protection after vaccination. Ten falcons vaccinated with an inactivated influenza virus (H5N2) vaccine seroconverted. We then challenged 5 vaccinated and 5 nonvaccinated falcons with HPAI (H5N1). All vaccinated birds survived; all unvaccinated birds died within 5 days. For the nonvaccinated birds, histopathologic examination showed tissue degeneration and necrosis, immunohistochemical techniques showed influenza virus antigen in affected tissues, and these birds shed high levels of infectious virus from the oropharynx and cloaca. Vaccinated birds showed no influenza virus antigen in tissues and shed virus at lower titers from the oropharynx only. Vaccination could protect these valuable birds and, through reduced virus shedding, reduce risk for transmission to other avian species and humans. PMID:18217549

Hafez, Hafez M.; Klopfleisch, Robert; Luschow, Dorte; Prusas, Christine; Teifke, Jens P.; Rudolf, Miriam; Grund, Christian; Kalthoff, Donata; Mettenleiter, Thomas; Beer, Martin; Harder, Timm

2007-01-01

384

A vaccine candidate of attenuated genotype VII Newcastle disease virus generated by reverse genetics  

Microsoft Academic Search

Genotype VII Newcastle disease virus (NDV) has been documented as the predominant epidemic genotype in China and some other Asian countries since 1990s. Recent work has demonstrated that NDV vaccines phylogenetically closer to epidemic viruses provide better protection than conventional vaccines in terms of reducing virus shedding and transmission. Since there is currently no available vaccine which possesses a close

Shunlin Hu; Huailiang Ma; Yantao Wu; Wenbo Liu; Xiaoquan Wang; Yuliang Liu; Xiufan Liu

2009-01-01

385

Virus-like particles as universal influenza vaccines  

PubMed Central

Current influenza vaccines are primarily targeted to induce immunity to the influenza virus strain-specific hemagglutinin antigen and are not effective in controlling outbreaks of new pandemic viruses. An approach for developing universal vaccines is to present highly conserved antigenic epitopes in an immunogenic conformation such as virus-like particles (VLPs) together with an adjuvant to enhance the vaccine immunogenicity. In this review, the authors focus on conserved antigenic targets and molecular adjuvants that were presented in VLPs. Conserved antigenic targets that include the hemagglutinin stalk domain, the external domain of influenza M2 and neuraminidase are discussed in addition to molecular adjuvants that are engineered to be incorporated into VLPs in a membrane-anchored form. PMID:23002980

Kang, Sang-Moo; Kim, Min-Chul; Compans, Richard W

2012-01-01

386

PURE CULTIVATION IN VIVO OF VACCINE VIRUS FREE FROM BACTERIA  

PubMed Central

Vaccine virus freed from all associated bacteria by means of suitable disinfecting agents can be propagated in a pure state in the testicles of rabbits and bulls. The virus cultivated in this manner is not only devoid of all bacteria, but appears capable of indefinite transfer from one animal to another. Sixty passages in rabbits of a pure strain have been made within one year. Several transfers from testicle to testicle are required to bring about accurate adaptation of the virus to the testicular parenchyma, so that continued propagation in this way can be certainly secured. During the first transfers from testicle to testicle the activity of the virus may be less than the original skin specimen from which the pure strain was derived; but as the transfers proceed the activity rises until, when the adaptation is complete, the activity of the testicular equals that of the skin strain. The multiplication of the virus within the testicle is maximum on the fourth or fifth day after inoculation; the quantity of virus remains about stationary until the eighth day, when diminution begins. At the expiration of five weeks no more virus could be detected in the testicle. The vaccinal processes in the skin, cornea, and testicle of rabbits are practically identical whether the virus employed for the inoculation has been the original skin strain or the pure testicular strain; and the skin lesions produced in the calf with the two strains are also identical. In conformity with the finding mentioned in the last paragraph it has been found that human beings react to the pure testicular strain of vaccine virus in an entirely typical manner. In the case both of original vaccination and revaccination the vaccinal effects cannot be distinguished from those arising from uncomplicated skin virus. Pure strains of testicular virus are readily produced, and once secured they may be propagated in a pure state by the method described in rabbits or bulls without difficulty and with economy. The pure strains thus obtained should supply an ideal form of virus for employment in the vaccination of human beings. PMID:19867889

Noguchi, Hideyo

1915-01-01

387

Delayed vaccine virus replication in chickens vaccinated subcutaneously with an immune complex infectious bursal disease vaccine: quantification of vaccine virus by real-time polymerase chain reaction.  

PubMed

The distribution of the immune complex vaccine virus for infectious bursal disease (IBD) in tissue was examined and the viral loads of the organs were quantitatively compared. One-day-old specific pathogen free (SPF) and maternally immune broiler chickens were injected subcutaneously with the vaccine. Lymphoid and non-lymphoid tissues were collected at various time intervals during the experiment to test for infectious bursal disease virus (IBDV)-RNA by using reverse transcriptase-polymerase chain reaction (RT-PCR). Only the bursa of Fabricius was found to be positive with unusually long viral persistence in the broiler group. The positive bursa samples were further investigated by using real-time PCR coupled with a TaqMan probe. The highest amounts of the virus were detected at its first appearance in the bursa: on day 14 post vaccination (PV) in the SPF chickens and on day 17 and day 21 PV in the maternally immune broiler group. The virus then gradually cleared, most likely due to the arallel appearance of the active immune response indicated by seroconversion. PMID:15971678

Iván, Judit; Velhner, Maja; Ursu, Krisztina; German, Péter; Mató, Tamás; Drén, Csaba Nick; Mészáros, János

2005-04-01

388

Varicella-Zoster Virus Vaccine: Molecular Genetics  

Microsoft Academic Search

\\u000a The genetic differences that potentially account for the attenuation of the Oka vaccine VZV preparation are more clearly defined\\u000a than for perhaps any other vaccine in current use. This is due in large part to the small number of differences between the\\u000a vaccine and the parental strain from which it was derived, and to the high level of genomic conservation

D. Scott Schmid

389

A plant-derived edible vaccine against hepatitis B virus.  

PubMed

The infectious hepatitis B virus represents 42 nm spherical double-shelled particles. However, analysis of blood from hepatitis B virus carriers revealed the presence of smaller 22 nm particles consisting of a viral envelope surface protein. These particles are highly immunogenic and have been used in the design of hepatitis B virus vaccine produced in yeast. Upon expression in yeast, these proteins form virus-like particles that are used for parenteral immunization. Therefore, the DNA fragment encoding hepatitis B virus surface antigen was introduced into Agrobacterium tumerifacience LBA4404 and used to obtain transgenic lupin (Lupinus luteus L.) and lettuce (Lactuca sativa L.) cv. Burpee Bibb expressing envelope surface protein. Mice that were fed the transgenic lupin tissue developed significant levels of hepatitis B virus-specific antibodies. Human volunteers, fed with transgenic lettuce plants expressing hepatitis B virus surface antigen, developed specific serum-IgG response to plant produced protein. PMID:10506582

Kapusta, J; Modelska, A; Figlerowicz, M; Pniewski, T; Letellier, M; Lisowa, O; Yusibov, V; Koprowski, H; Plucienniczak, A; Legocki, A B

1999-10-01

390

A Recombinant Hendra Virus G Glycoprotein Subunit Vaccine Protects Nonhuman Primates against Hendra Virus Challenge  

PubMed Central

ABSTRACT Hendra virus (HeV) is a zoonotic emerging virus belonging to the family Paramyxoviridae. HeV causes severe and often fatal respiratory and/or neurologic disease in both animals and humans. Currently, there are no licensed vaccines or antiviral drugs approved for human use. A number of animal models have been developed for studying HeV infection, with the African green monkey (AGM) appearing to most faithfully reproduce the human disease. Here, we assessed the utility of a newly developed recombinant subunit vaccine based on the HeV attachment (G) glycoprotein in the AGM model. Four AGMs were vaccinated with two doses of the HeV vaccine (sGHeV) containing Alhydrogel, four AGMs received the sGHeV with Alhydrogel and CpG, and four control animals did not receive the sGHeV vaccine. Animals were challenged with a high dose of infectious HeV 21 days after the boost vaccination. None of the eight specifically vaccinated animals showed any evidence of clinical illness and survived the challenge. All four controls became severely ill with symptoms consistent with HeV infection, and three of the four animals succumbed 8 days after exposure. Success of the recombinant subunit vaccine in AGMs provides pivotal data in supporting its further preclinical development for potential human use. IMPORTANCE A Hendra virus attachment (G) glycoprotein subunit vaccine was tested in nonhuman primates to assess its ability to protect them from a lethal infection with Hendra virus. It was found that all vaccinated African green monkeys were completely protected against subsequent Hendra virus infection and disease. The success of this new subunit vaccine in nonhuman primates provides critical data in support of its further development for future human use. PMID:24522928

Mire, Chad E.; Geisbert, Joan B.; Agans, Krystle N.; Feng, Yan-Ru; Fenton, Karla A.; Bossart, Katharine N.; Yan, Lianying; Chan, Yee-Peng; Geisbert, Thomas W.

2014-01-01

391

Virus-Like Particle Vaccine Induces Protective Immunity against Homologous and Heterologous Strains of Influenza Virus  

Microsoft Academic Search

Recurrent outbreaks of highly pathogenic avian influenza virus pose the threat of pandemic spread of lethal disease and make it a priority to develop safe and effective vaccines. Influenza virus-like particles (VLPs) have been suggested to be a promising vaccine approach. However, VLP-induced immune responses, and their roles in inducing memory immune responses and cross-protective immunity have not been investigated.

Fu-Shi Quan; Chunzi Huang; Richard W. Compans; Sang-Moo Kang

2007-01-01

392

Ebola virus: immune mechanisms of protection and vaccine development.  

PubMed

Vaccination is one of our most powerful antiviral strategies. Despite the emergence of deadly viruses such as Ebola virus, vaccination efforts have focused mainly on childhood communicable diseases. Although Ebola virus was once believed to be limited to isolated outbreaks in distant lands, forces of globalization potentiate outbreaks anywhere in the world through incidental transmission. Moreover, since this virus has already been transformed into weapon-grade material, the potential exists for it to be used as a biological weapon with catastrophic consequences for any population vulnerable to attack. Ebola hemorrhagic fever (EHF) is a syndrome that can rapidly lead to death within days of symptom onset. The disease directly affects the immune system and vascular bed, with correspondingly high mortality rates. Patients with severe disease produce dangerously high levels of inflammatory cytokines, which destroy normal tissue and microcirculation, leading to profound capillary leakage, renal failure, and disseminated intravascular coagulation. Vaccine development has been fraught with obstacles, primarily of a biosafety nature. Case reports of acutely ill patients with EHF showing improvement with the transfusion of convalescent plasma are at odds with animal studies demonstrating further viral replication with the same treatment. Using mRNA extracted from bone marrow of Ebola survivors, human monoclonal antibodies against Ebola virus surface protein have been experimentally produced and now raise the hope for the development of a safe vaccine. PMID:12698920

Nyamathi, Adeline M; Fahey, John L; Sands, Heather; Casillas, Adrian M

2003-04-01

393

UNCORRECTEDPROOF Please cite this article in press as: Liu X, et al. Genetic engineering of a modified herpes simplex virus 1 vaccine vector. Vaccine (2009),  

E-print Network

of a modified herpes simplex virus 1 vaccine vector. Vaccine (2009), doi:10.1016/j.vaccine.2009.03.003 ARTICLE journal homepage: www.elsevier.com/locate/vaccine Genetic engineering of a modified herpes simplex virus 1 HSV-114 d106S15 Vaccine vector16 a b s t r a c t The herpes simplex virus 1 (HSV-1) d106 mutant virus

Knipe, David M.

394

Bovine viral diarrhea virus types 1 and 2 antibody response in calves receiving modified live virus or inactivated vaccines  

Microsoft Academic Search

Serums from calves receiving eight different commercial vaccines containing modified live virus (MLV) or inactivated bovine viral diarrhea virus (BVDV) immunogens were assayed for antibodies to types 1 and 2 BVDV strains. The immune response to the types 1 and 2 BVDV strains were evaluated in 48 calves receiving one of the eight vaccines for each group. For 7\\/8 vaccines,

Robert W Fulton; Lurinda J Burge

2000-01-01

395

Genetically engineered Mengo virus vaccination of multiple captive wildlife species.  

PubMed

Encephalomyocarditis virus (EMCV), has caused the deaths of many species of animals in zoological parks and research institutions. The Audubon Park Zoo, (New Orleans, Louisiana, USA) attempted vaccination of several species with a killed EMCV vaccine with mixed results. This paper reports an attempt at vaccination against EMCV using a genetically engineered, live attenuated Mengo virus (vMC0) at the Audubon Park Zoo and Miami Metro Zoo, (Miami, Florida, USA) from December 1996 to June 1997. Several species of animals were vaccinated with vMC0, which is serologically indistinguishable from the field strain of EMCV. Serum samples were taken at the time of vaccination and again 21 days later, then submitted for serum neutralization titers against EMCV. The vaccinate species included red capped mangebey (Cercocebus torquatus), colobus (Colobus guereza), angolan colobus (Colobus angolensis), ruffed lemur (Lemur variegatus ruber and Lemur variegatus variegatus), back lemur (Lemur macaco), ring-tailed lemur (Lemur catta), siamang (Hylobates syndactylus), diana guenon (Cercopithicus diana), spider monkey (Ateles geoffroyi), common marmoset (Callithrix jacchus), talapoin monkey (Cercopithecus talapoin), Brazilian tapir (Tapirus terrestris), Baird's tapir (Tapirus bairdii), Malayan tapir (Tapirus indicus), dromedary camel (Camelus dromedarius), bactrian camel (Camelus bactrianus), gerenuk (Litocranius walleri), guanaco (Lama glama guanicoe), black duiker (Cephalophus niger), Vietnamese potbellied pig (Sus scrofa), babirusa (Babyrousa babyrussa), collard peccary (Tayass tajacu), and African crested porcupine (Hystrix africaeaustralis). The vaccine response was variable, with high virus neutralizing antibody titer responses in some primate species and mixed to poor responses for other species. No ill effects were seen with vaccination. PMID:10231768

Backues, K A; Hill, M; Palmenberg, A C; Miller, C; Soike, K F; Aguilar, R

1999-04-01

396

Antibody responses by cattle after vaccination with commercial viral vaccines containing bovine herpesvirus-1, bovine viral diarrhea virus, parainfluenza-3 virus, and bovine respiratory syncytial virus immunogens and subsequent revaccination at day 140  

Microsoft Academic Search

Calves were vaccinated with four different commercial viral vaccines containing bovine herpesvirus-1 (BHV-1), bovine viral diarrhea (BVDV), parainfluenza-3 virus (PI-3V), and bovine respiratory syncytial virus (BRSV) immunogens. For the initial vaccination certain vaccines were given twice (days 0 and 28), whereas other vaccines were given on day 0. The calves received another injection on day 140 with the vaccine originally

Robert W. Fulton; A. W. Confer; Lurinda J. Burge; Louis J. Perino; J. M. d'Offay; Mark E. Payton; R. E. Mock

1995-01-01

397

Infection of influenza virus neuraminidase-vaccinated mice with homologous influenza virus leads to strong protection against heterologous influenza viruses.  

PubMed

Vaccination is the best measure to prevent influenza pandemics. Here, we studied the protective effect against heterologous influenza viruses, including A/reassortant/NYMC X-179A (pH1N1), A/Chicken/Henan/12/2004 (H5N1), A/Chicken/Jiangsu/7/2002 (H9N2) and A/Guizhou/54/89×A/PR/8/34 (A/Guizhou-X) (H3N2), in mice first vaccinated with a DNA vaccine of haemagglutinin (HA) or neuraminidase (NA) of A/PR/8/34 (PR8) and then infected with the homologous virus. We showed that PR8 HA or NA vaccination both protected mice against a lethal dose of the homologous virus; PR8 HA or NA DNA vaccination and then PR8 infection in mice offered poor or excellent protection, respectively, against a second, heterologous influenza virus challenge. In addition, before the second heterologous influenza infection, the highest antibody level against nucleoprotein (NP) and matrix (M1 and M2) proteins was found in the PR8 NA-vaccinated and PR8-infected group. The level of induced cellular immunity against NP and M1 showed a trend consistent with that seen in antibody levels. However, PR8 HA+NA vaccination and then PR8 infection resulted in limited protection against heterologous influenza virus challenge. Results of the present study demonstrated that infection of the homologous influenza virus in mice already immunized with a NA vaccine could provide excellent protection against subsequent infection of a heterologous influenza virus. These findings suggested that NA, a major antigen of influenza virus, could be an important candidate antigen for universal influenza vaccines. PMID:25170051

He, Biao; Chang, Haiyan; Liu, Zhihua; Huang, Chaoyang; Liu, Xueying; Zheng, Dan; Fang, Fang; Sun, Bing; Chen, Ze

2014-12-01

398

Selecting Viruses for the Seasonal Influenza Vaccine  

MedlinePLUS

... PCR and Other Molecular Assays for Diagnosis of Influenza Virus Infection Clinical Signs and Symptoms of Influenza International ... influenza. This involves receiving and testing thousands of influenza virus samples from patients with suspected flu illness. The ...

399

Vaccinia Virus Proteins A52 and B14 Share a Bcl-2-Like Fold but Have Evolved to Inhibit NF-?B rather than Apoptosis  

PubMed Central

Vaccinia virus (VACV), the prototype poxvirus, encodes numerous proteins that modulate the host response to infection. Two such proteins, B14 and A52, act inside infected cells to inhibit activation of NF-?B, thereby blocking the production of pro-inflammatory cytokines. We have solved the crystal structures of A52 and B14 at 1.9 Ĺ and 2.7 Ĺ resolution, respectively.