Articoli di riviste: "Vaccinia virus"

1

Tartaglia, James, e Enzo Paoletti. "Recombinant vaccinia virus vaccines". Trends in Biotechnology 6, n. 2 (febbraio 1988): 43–46. http://dx.doi.org/10.1016/0167-7799(88)90035-2.

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Doria-Rose, N. A., C. Ohlen, P. Polacino, C. C. Pierce, M. T. Hensel, L. Kuller, T. Mulvania et al. "Multigene DNA Priming-Boosting Vaccines Protect Macaques from Acute CD4+-T-Cell Depletion after Simian-Human Immunodeficiency Virus SHIV89.6P Mucosal Challenge". Journal of Virology 77, n. 21 (1 novembre 2003): 11563–77. http://dx.doi.org/10.1128/jvi.77.21.11563-11577.2003.

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ABSTRACT We evaluated four priming-boosting vaccine regimens for the highly pathogenic simian human immunodeficiency virus SHIV89.6P in Macaca nemestrina. Each regimen included gene gun delivery of a DNA vaccine expressing all SHIV89.6 genes plus Env gp160 of SHIV89.6P. Additional components were two recombinant vaccinia viruses, expressing SHIV89.6 Gag-Pol or Env gp160, and inactivated SHIV89.6 virus. We compared (i) DNA priming/DNA boosting, (ii) DNA priming/inactivated virus boosting, (iii) DNA priming/vaccinia virus boosting, and (iv) vaccinia virus priming/DNA boosting versus sham vaccines in groups of 6 macaques. Prechallenge antibody responses to Env and Gag were strongest in the groups that received vaccinia virus priming or boosting. Cellular immunity to SHIV89.6 peptides was measured by enzyme-linked immunospot assay; strong responses to Gag and Env were found in 9 of 12 vaccinia virus vaccinees and 1 of 6 DNA-primed/inactivated-virus-boosted animals. Vaccinated macaques were challenged intrarectally with 50 50% animal infectious doses of SHIV89.6P 3 weeks after the last immunization. All animals became infected. Five of six DNA-vaccinated and 5 of 6 DNA-primed/particle-boosted animals, as well as all 6 controls, experienced severe CD4+-T-cell loss in the first 3 weeks after infection. In contrast, DNA priming/vaccinia virus boosting and vaccinia virus priming/DNA boosting vaccines both protected animals from disease: 11 of 12 macaques had no loss of CD4+ T cells or moderate declines. Virus loads in plasma at the set point were significantly lower in vaccinia virus-primed/DNA-boosted animals versus controls (P = 0.03). We conclude that multigene vaccines delivered by a combination of vaccinia virus and gene gun-delivered DNA were effective against SHIV89.6P viral challenge in M. nemestrina.

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KUTINOVA, L. "Search for optimal parent for recombinant vaccinia virus vaccines. Study of three vaccinia virus vaccinal strains and several virus lines derived from them". Vaccine 13, n. 5 (1995): 487–93. http://dx.doi.org/10.1016/0264-410x(94)00019-j.

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Precopio, Melissa L., Michael R. Betts, Janie Parrino, David A. Price, Emma Gostick, David R. Ambrozak, Tedi E. Asher et al. "Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8+ T cell responses". Journal of Experimental Medicine 204, n. 6 (29 maggio 2007): 1405–16. http://dx.doi.org/10.1084/jem.20062363.

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Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8+ T cells induced by vaccinia virus immunization in a comparative vaccine trial of modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which protection was assessed against subsequent Dryvax challenge. Vaccinia virus–specific CD8+ T cells induced by both MVA and Dryvax were highly polyfunctional; they degranulated and produced interferon γ, interleukin 2, macrophage inflammatory protein 1β, and tumor necrosis factor α after antigenic stimulation. Responding CD8+ T cells exhibited an unusual phenotype (CD45RO−CD27intermediate). The unique phenotype and high degree of polyfunctionality induced by vaccinia virus also extended to inserted HIV gene products of recombinant NYVAC. This quality of the CD8+ T cell response may be at least partially responsible for the profound efficacy of these vaccines in protection against smallpox and serves as a benchmark against which other vaccines can be evaluated.

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Truong, Cao-Sang, e So Young Yoo. "Oncolytic Vaccinia Virus in Lung Cancer Vaccines". Vaccines 10, n. 2 (4 febbraio 2022): 240. http://dx.doi.org/10.3390/vaccines10020240.

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Therapeutic cancer vaccines represent a promising therapeutic modality via the induction of long-term immune response and reduction in adverse effects by specifically targeting tumor-associated antigens. Oncolytic virus, especially vaccinia virus (VV) is a promising cancer treatment option for effective cancer immunotherapy and thus can also be utilized in cancer vaccines. Non-small cell lung cancer (NSCLC) is likely to respond to immunotherapy, such as immune checkpoint inhibitors or cancer vaccines, since it has a high tumor mutational burden. In this review, we will summarize recent applications of VV in lung cancer treatment and discuss the potential and direction of VV-based therapeutic vaccines.

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Jacobs, Bertram L., Jeffrey O. Langland, Karen V. Kibler, Karen L. Denzler, Stacy D. White, Susan A. Holechek, Shukmei Wong, Trung Huynh e Carole R. Baskin. "Vaccinia virus vaccines: Past, present and future". Antiviral Research 84, n. 1 (ottobre 2009): 1–13. http://dx.doi.org/10.1016/j.antiviral.2009.06.006.

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Smith, Geoffrey L., Brendan J. Murphy e Mansun Law. "Vaccinia Virus Motility". Annual Review of Microbiology 57, n. 1 (ottobre 2003): 323–42. http://dx.doi.org/10.1146/annurev.micro.57.030502.091037.

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Perkus, M. E. "RECOMBINANT VACCINIA VIRUS". Pediatric Infectious Disease Journal 5, n. 2 (marzo 1986): 284. http://dx.doi.org/10.1097/00006454-198603000-00045.

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Broyles, Steven S. "Vaccinia virus transcription". Journal of General Virology 84, n. 9 (1 settembre 2003): 2293–303. http://dx.doi.org/10.1099/vir.0.18942-0.

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Stittelaar, Koert J., Geert van Amerongen, Ivanela Kondova, Thijs Kuiken, Rob F. van Lavieren, Frank H. M. Pistoor, Hubert G. M. Niesters et al. "Modified Vaccinia Virus Ankara Protects Macaques against Respiratory Challenge with Monkeypox Virus". Journal of Virology 79, n. 12 (15 giugno 2005): 7845–51. http://dx.doi.org/10.1128/jvi.79.12.7845-7851.2005.

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ABSTRACT The use of classical smallpox vaccines based on vaccinia virus (VV) is associated with severe complications in both naïve and immune individuals. Modified vaccinia virus Ankara (MVA), a highly attenuated replication-deficient strain of VV, has been proven to be safe in humans and immunocompromised animals, and its efficacy against smallpox is currently being addressed. Here we directly compare the efficacies of MVA alone and in combination with classical VV-based vaccines in a cynomolgus macaque monkeypox model. The MVA-based smallpox vaccine protected macaques against a lethal respiratory challenge with monkeypox virus and is therefore an important candidate for the protection of humans against smallpox.

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Ober, B. T., P. Brühl, M. Schmidt, V. Wieser, W. Gritschenberger, S. Coulibaly, H. Savidis-Dacho, M. Gerencer e F. G. Falkner. "Immunogenicity and Safety of Defective Vaccinia Virus Lister: Comparison with Modified Vaccinia Virus Ankara". Journal of Virology 76, n. 15 (1 agosto 2002): 7713–23. http://dx.doi.org/10.1128/jvi.76.15.7713-7723.2002.

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ABSTRACT Potent and safe vaccinia virus vectors inducing cell-mediated immunity are needed for clinical use. Replicating vaccinia viruses generally induce strong cell-mediated immunity; however, they may have severe adverse effects. As a vector for clinical use, we assessed the defective vaccinia virus system, in which deletion of an essential gene blocks viral replication, resulting in an infectious virus that does not multiply in the host. The vaccinia virus Lister/Elstree strain, used during worldwide smallpox eradication, was chosen as the parental virus. The immunogenicity and safety of the defective vaccinia virus Lister were evaluated without and with the inserted human p53 gene as a model and compared to parallel constructs based on modified vaccinia virus Ankara (MVA), the present “gold standard” of recombinant vaccinia viruses in clinical development. The defective viruses induced an efficient Th1-type immune response. Antibody and cytotoxic-T-cell responses were comparable to those induced by MVA. Safety of the defective Lister constructs could be demonstrated in vitro in cell culture as well as in vivo in immunodeficient SCID mice. Similar to MVA, the defective viruses were tolerated at doses four orders of magnitude higher than those of the wild-type Lister strain. While current nonreplicating vectors are produced mainly in primary chicken cells, defective vaccinia virus is produced in a permanent safety-tested cell line. Vaccines based on this system have the additional advantage of enhanced product safety. Therefore, a vector system was made which promises to be a valuable tool not only for immunotherapy for diseases such as cancer, human immunodeficiency virus infection, or malaria but also as a basis for a safer smallpox vaccine.

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Kaufman, David R., Jaap Goudsmit, Lennart Holterman, Bonnie A. Ewald, Matthew Denholtz, Colleen Devoy, Ayush Giri et al. "Differential Antigen Requirements for Protection against Systemic and Intranasal Vaccinia Virus Challenges in Mice". Journal of Virology 82, n. 14 (30 aprile 2008): 6829–37. http://dx.doi.org/10.1128/jvi.00353-08.

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

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Ahmed, Syed Faraz, Muhammad Saqib Sohail, Ahmed Abdul Quadeer e Matthew R. McKay. "Vaccinia-Virus-Based Vaccines Are Expected to Elicit Highly Cross-Reactive Immunity to the 2022 Monkeypox Virus". Viruses 14, n. 9 (3 settembre 2022): 1960. http://dx.doi.org/10.3390/v14091960.

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Beginning in May 2022, a novel cluster of monkeypox virus infections was detected in humans. This virus has spread rapidly to non-endemic countries, sparking global concern. Specific vaccines based on the vaccinia virus (VACV) have demonstrated high efficacy against monkeypox viruses in the past and are considered an important outbreak control measure. Viruses observed in the current outbreak carry distinct genetic variations that have the potential to affect vaccine-induced immune recognition. Here, by investigating genetic variation with respect to orthologous immunogenic vaccinia-virus proteins, we report data that anticipates immune responses induced by VACV-based vaccines, including the currently available MVA-BN and ACAM2000 vaccines, to remain highly cross-reactive against the newly observed monkeypox viruses.

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Hruby, D. E. "Vaccinia virus vectors: new strategies for producing recombinant vaccines." Clinical Microbiology Reviews 3, n. 2 (aprile 1990): 153–70. http://dx.doi.org/10.1128/cmr.3.2.153.

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The development and continued refinement of techniques for the efficient insertion and expression of heterologous DNA sequences from within the genomic context of infectious vaccinia virus recombinants are among the most promising current approaches towards effective immunoprophylaxis against a variety of protozoan, viral, and bacterial human pathogens. Because of its medical relevance, this area is the subject of intense research interest and has evolved rapidly during the past several years. This review (i) provides an updated overview of the technology that exists for assembling recombinant vaccinia virus strains, (ii) discusses the advantages and disadvantages of these approaches, (iii) outlines the areas of outgoing research directed towards overcoming the limitations of current techniques, and (iv) provides some insight (i.e., speculation) about probable future refinements in the use of vaccinia virus as a vector.

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Maksyutov, Rinat A., Elena V. Gavrilova, Galina V. Kochneva e Sergei N. Shchelkunov. "Immunogenicity and Protective Efficacy of a Polyvalent DNA Vaccine against Human Orthopoxvirus Infections Based on Smallpox Virus Genes". Journal of Vaccines 2013 (21 agosto 2013): 1–8. http://dx.doi.org/10.1155/2013/618324.

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

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Sebastian, Sarah, e Sarah C. Gilbert. "Recombinant modified vaccinia virus Ankara-based malaria vaccines". Expert Review of Vaccines 15, n. 1 (29 ottobre 2015): 91–103. http://dx.doi.org/10.1586/14760584.2016.1106319.

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Gilbert, Sarah C. "Clinical development of Modified Vaccinia virus Ankara vaccines". Vaccine 31, n. 39 (settembre 2013): 4241–46. http://dx.doi.org/10.1016/j.vaccine.2013.03.020.

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Paoletti, Enzo, Marion E. Perkus e Antonia Piccini. "Live recombinant vaccines using genetically engineered vaccinia virus". Antiviral Research 5 (gennaio 1985): 301–7. http://dx.doi.org/10.1016/s0166-3542(85)80042-5.

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Kaplan, C. "Vaccinia virus: a suitable vehicle for recombinant vaccines?" Archives of Virology 106, n. 1-2 (marzo 1989): 127–39. http://dx.doi.org/10.1007/bf01311044.

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Hughes, Christine M., Frances K. Newman, Whitni B. Davidson, Victoria A. Olson, Scott K. Smith, Robert C. Holman, Lihan Yan et al. "Analysis of Variola and Vaccinia Virus Neutralization Assays for Smallpox Vaccines". Clinical and Vaccine Immunology 19, n. 7 (16 maggio 2012): 1116–18. http://dx.doi.org/10.1128/cvi.00056-12.

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ABSTRACTPossible smallpox reemergence drives research for third-generation vaccines that effectively neutralize variola virus. A comparison of neutralization assays using different substrates, variola and vaccinia (Dryvax and modified vaccinia Ankara [MVA]), showed significantly different 90% neutralization titers; Dryvax underestimated while MVA overestimated variola neutralization. Third-generation vaccines may rely upon neutralization as a correlate of protection.

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Watanabe, Shumpei, Tomoki Yoshikawa, Yoshihiro Kaku, Takeshi Kurosu, Shuetsu Fukushi, Satoko Sugimoto, Yuki Nishisaka et al. "Construction of a recombinant vaccine expressing Nipah virus glycoprotein using the replicative and highly attenuated vaccinia virus strain LC16m8". PLOS Neglected Tropical Diseases 17, n. 12 (15 dicembre 2023): e0011851. http://dx.doi.org/10.1371/journal.pntd.0011851.

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Nipah virus (NiV) is a highly pathogenic zoonotic virus that causes severe encephalitis and respiratory diseases and has a high mortality rate in humans (>40%). Epidemiological studies on various fruit bat species, which are natural reservoirs of the virus, have shown that NiV is widely distributed throughout Southeast Asia. Therefore, there is an urgent need to develop effective NiV vaccines. In this study, we generated recombinant vaccinia viruses expressing the NiV glycoprotein (G) or fusion (F) protein using the LC16m8 strain, and examined their antigenicity and ability to induce immunity. Neutralizing antibodies against NiV were successfully induced in hamsters inoculated with LC16m8 expressing NiV G or F, and the antibody titers were higher than those induced by other vaccinia virus vectors previously reported to prevent lethal NiV infection. These findings indicate that the LC16m8-based vaccine format has superior features as a proliferative vaccine compared with other poxvirus-based vaccines. Moreover, the data collected over the course of antibody elevation during three rounds of vaccination in hamsters provide an important basis for the clinical use of vaccinia virus-based vaccines against NiV disease. Trial Registration: NCT05398796.

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Verardi, Paulo H., Allison Titong e Caitlin J. Hagen. "A vaccinia virus renaissance". Human Vaccines & Immunotherapeutics 8, n. 7 (luglio 2012): 961–70. http://dx.doi.org/10.4161/hv.21080.

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Zaslavsky, V. "Uncoating of vaccinia virus." Journal of Virology 55, n. 2 (1985): 352–56. http://dx.doi.org/10.1128/jvi.55.2.352-356.1985.

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MOSS, BERNARD, e CHARLES FLEXNER. "Vaccinia Virus Expression Vectors". Annals of the New York Academy of Sciences 569, n. 1 Biomedical Sc (dicembre 1989): 86–103. http://dx.doi.org/10.1111/j.1749-6632.1989.tb27360.x.

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Smith, Geoffrey L., Julian A. Symons, Anu Khanna, Alain Vanderplasschen e Antonio Alcami. "Vaccinia virus immune evasion". Immunological Reviews 159, n. 1 (ottobre 1997): 137–54. http://dx.doi.org/10.1111/j.1600-065x.1997.tb01012.x.

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Yakubitskiy, S. N., I. V. Kolosova, R. A. Maksyutov e S. N. Shchelkunov. "Attenuation of Vaccinia Virus". Acta Naturae 7, n. 4 (15 dicembre 2015): 113–21. http://dx.doi.org/10.32607/20758251-2015-7-4-113-121.

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Since 1980, in the post-smallpox vaccination era the human population has become increasingly susceptible compared to a generation ago to not only the variola (smallpox) virus, but also other zoonotic orthopoxviruses. The need for safer vaccines against orthopoxviruses is even greater now. The Lister vaccine strain (LIVP) of vaccinia virus was used as a parental virus for generating a recombinant 1421ABJCN clone defective in five virulence genes encoding hemagglutinin (A56R), the IFN--binding protein (B8R), thymidine kinase (J2R), the complement-binding protein (C3L), and the Bcl-2-like inhibitor of apoptosis (N1L). We found that disruption of these loci does not affect replication in mammalian cell cultures. The isogenic recombinant strain 1421ABJCN exhibits a reduced inflammatory response and attenuated neurovirulence relative to LIVP. Virus titers of 1421ABJCN were 3 lg lower versus the parent VACV LIVP when administered by the intracerebral route in new-born mice. In a subcutaneous mouse model, 1421ABJCN displayed levels of VACV-neutralizing antibodies comparable to those of LIVP and conferred protective immunity against lethal challenge by the ectromelia virus. The VACV mutant holds promise as a safe live vaccine strain for preventing smallpox and other orthopoxvirus infections.

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Smith, Geoffrey L. "Vaccinia virus immune evasion". Immunology Letters 65, n. 1-2 (gennaio 1999): 55–62. http://dx.doi.org/10.1016/s0165-2478(98)00125-4.

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Mackett, M., e G. L. Smith. "Vaccinia Virus Expression Vectors". Journal of General Virology 67, n. 10 (1 ottobre 1986): 2067–82. http://dx.doi.org/10.1099/0022-1317-67-10-2067.

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Moss, B., e C. Flexner. "Vaccinia Virus Expression Vectors". Annual Review of Immunology 5, n. 1 (aprile 1987): 305–24. http://dx.doi.org/10.1146/annurev.iy.05.040187.001513.

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Bielinska, Anna U., Alexander A. Chepurnov, Jeffrey J. Landers, Katarzyna W. Janczak, Tatiana S. Chepurnova, Gary D. Luker e James R. Baker. "A Novel, Killed-Virus Nasal Vaccinia Virus Vaccine". Clinical and Vaccine Immunology 15, n. 2 (5 dicembre 2007): 348–58. http://dx.doi.org/10.1128/cvi.00440-07.

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ABSTRACT Live-virus vaccines for smallpox are effective but have risks that are no longer acceptable for routine use in populations at minimal risk of infection. We have developed a mucosal, killed-vaccinia virus (VV) vaccine based on antimicrobial nanoemulsion (NE) of soybean oil and detergent. Incubation of VV with 10% NE for at least 60 min causes the complete disruption and inactivation of VV. Simple mixtures of NE and VV (Western Reserve serotype) (VV/NE) applied to the nares of mice resulted in both systemic and mucosal anti-VV immunity, virus-neutralizing antibodies, and Th1-biased cellular responses. Nasal vaccination with VV/NE vaccine produced protection against lethal infection equal to vaccination by scarification, with 100% survival after challenge with 77 times the 50% lethal dose of live VV. However, animals protected with VV/NE immunization did after virus challenge have clinical symptoms more extensive than animals vaccinated by scarification. VV/NE-based vaccines are highly immunogenic and induce protective mucosal and systemic immunity without the need for an inflammatory adjuvant or infection with live virus.

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Ye, Chunting, Jang Gi Choi, Sojan Abraham, Premlata Shankar e Manjunath Swamy. "Targeting DNA vaccines to dendritic cells using a small peptide to enhance immune response (VAC4P.1110)". Journal of Immunology 194, n. 1_Supplement (1 maggio 2015): 72.15. http://dx.doi.org/10.4049/jimmunol.194.supp.72.15.

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Abstract Dendritic cell targeting of antigens greatly enhances immunogenicity. Although there are several reagents (DEC205, Dectin-1, Langerin, Clec9, nanoparticle, etc) to target protein antigens to DCs, there is still no method to target DNA vaccines directly to DCs. Here we show that a small peptide derived from the rabies virus glycoprotein, fused to protamine residues (RVG-P) can target DNA to DCs resulting in enhanced T-cell and humoral responses. Targeted delivery of DNA vaccine encoding the immunodominant Vaccinia virus B8R gene to DCs with RVG-P was able to re-stimulate Vaccinia-specific memory T cells in vitro. Moreover, a single iv injection of B8R gene bound to RVG-P without any adjuvants was able prime a Vaccinia-specific T-cell response that was able to rapidly clear a subsequent Vaccinia virus challenge in mice. Finally, immunization of mice with a DNA vaccine encoding with West Nile virus (WNV) prM and E proteins via RVG-P elicited high titers of WN neutralizing antibodies that protected mice from lethal WNV challenge. Thus, RVG-P provides a tool to target DNA vaccines to DCs to elicit robust T-cell and humoral immune responses.

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Whitehouse, Erin R., Agam Rao, Yon Yu, Patricia Yu, Margaret Griffin, Susan E. Gorman, Kristen A. Angel et al. "1207. Vaccinia Virus Infection Acquired from an Occupational Needlestick—San Diego, California, 2019". Open Forum Infectious Diseases 6, Supplement_2 (ottobre 2019): S434. http://dx.doi.org/10.1093/ofid/ofz360.1070.

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Abstract Background Vaccinia virus, a virus similar to but less virulent than variola virus, is a component of smallpox vaccines and increasingly used for medical research. Vaccinia immunoglobulin intravenous (VIGIV) and tecovirimat are stockpiled in the U.S. Strategic National Stockpile (SNS) for potential smallpox bioterror events, but only VIGIV is licensed for vaccinia treatment. On January 12, 2019, CDC was consulted for worsening infection in a laboratory worker after a needlestick with vaccinia. Methods We investigated demographic, clinical, vaccination, and exposure history and determined likelihood of vaccinia virus infection. Identity of the specific strain was sought because some have genetic modifications that might impact virulence. Discussions among stakeholders informed treatment decisions and facilitated medication access and usage. Swabs from the lesion were tested by real-time polymerase chain reaction for orthopoxvirus DNA, which includes vaccinia. Results The affected worker was an otherwise healthy 26-year-old woman who developed a pustular lesion at the needlestick site on her left index finger (Image). The patient had been injecting vaccinia virus into a mouse and had declined nationally recommended vaccination. Edema, lymphadenopathy, and fever raised concern for severe illness; neither the patient nor occupational health were certain of the vaccinia strain type. CDC, SNS, local health departments, drug manufacturers, and clinicians rapidly collaborated to make treatment decisions based on available information and ensure delivery of both biologics and administration of tecovirimat under an expanded access investigational new drug protocol. Eventually, a wound swab tested positive and the strain was determined to be one with no known impact on virulence. Conclusion With increasing use of vaccinia in research, occupational infections may continue to occur. Health clinics should extensively counsel staff who decline vaccination and have documentation on-hand about vaccinia virus types to inform treatment decisions. This response prompted CDC to develop outreach materials specifically for occupational vaccinia exposures. Disclosures All authors: No reported disclosures.

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Holzer, G. W., G. Remp, G. Antoine, M. Pfleiderer, O. M. Enzersberger, W. Emsenhuber, T. Hämmerle et al. "Highly Efficient Induction of Protective Immunity by a Vaccinia Virus Vector Defective in Late Gene Expression". Journal of Virology 73, n. 6 (1 giugno 1999): 4536–42. http://dx.doi.org/10.1128/jvi.73.6.4536-4542.1999.

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ABSTRACT Vaccinia viruses defective in the essential gene coding for the enzyme uracil DNA glycosylase (UDG) do not undergo DNA replication and do not express late genes in wild-type cells. A UDG-deficient vaccinia virus vector carrying the tick-borne encephalitis (TBE) virus prM/E gene, termed vD4-prME, was constructed, and its potential as a vaccine vector was evaluated. High-level expression of the prM/E antigens could be demonstrated in infected complementing cells, and moderate levels were found under noncomplementing conditions. The vD4-prME vector was used to vaccinate mice; animals receiving single vaccination doses as low as 104 PFU were fully protected against challenge with high doses of virulent TBE virus. Single vaccination doses of 103 PFU were sufficient to induce significant neutralizing antibody titers. With the corresponding replicating virus, doses at least 10-fold higher were needed to achieve protection. The data indicate that late gene expression of the vaccine vector is not required for successful vaccination; early vaccinia virus gene expression induces a potent protective immune response. The new vaccinia virus-based defective vectors are therefore promising live vaccines for prophylaxis and cancer immunotherapy.

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Meseda, Clement A., Anne E. Mayer, Arunima Kumar, Alonzo D. Garcia, Joseph Campbell, Paul Listrani, Jody Manischewitz et al. "Comparative Evaluation of the Immune Responses and Protection Engendered by LC16m8 and Dryvax Smallpox Vaccines in a Mouse Model". Clinical and Vaccine Immunology 16, n. 9 (15 luglio 2009): 1261–71. http://dx.doi.org/10.1128/cvi.00040-09.

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ABSTRACT The immune response elicited by LC16m8, a candidate smallpox vaccine that was developed in Japan by cold selection during serial passage of the Lister vaccine virus in primary rabbit kidney cells, was compared to Dryvax in a mouse model. LC16m8 carries a mutation resulting in the truncation of the B5 protein, an important neutralizing target of the extracellular envelope form of vaccinia virus (EV). LC16m8 elicited a broad-spectrum immunoglobulin G (IgG) response that neutralized both EV and the intracellular mature form of vaccinia virus and provoked cell-mediated immune responses, including the activation of CD4+ and CD8+ cells, similarly to Dryvax. Mice inoculated with LC16m8 had detectable but low levels of anti-B5 IgG compared to Dryvax, but both Dryvax and LC16m8 sera neutralized vaccinia virus EV in vitro. A truncated B5 protein (∼8 kDa) was expressed abundantly in LC16m8-infected cells, and both murine immune sera and human vaccinia virus immunoglobulin recognized the truncated recombinant B5 protein in antigen-specific enzyme-linked immunosorbent assays. At a high-dose intranasal challenge (100 or 250 50% lethal doses), LC16m8 and Dryvax conferred similar levels of protection against vaccinia virus strain WR postvaccination. Taken together, the results extend our current understanding of the protective immune responses elicited by LC16m8 and indicate that the relative efficacy in a mouse model rivals that of previously licensed smallpox vaccines.

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35

Adamo, Joan E., Clement A. Meseda, Jerry P. Weir e Michael J. Merchlinsky. "Smallpox vaccines induce antibodies to the immunomodulatory, secreted vaccinia virus complement control protein". Journal of General Virology 90, n. 11 (1 novembre 2009): 2604–8. http://dx.doi.org/10.1099/vir.0.008474-0.

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Vaccination with Dryvax elicits a broad humoral response against many viral proteins. Human vaccinia immune globulin was used to screen the secreted proteins from cells infected with Dryvax or the candidate smallpox vaccine LC16m8 to determine whether the protective humoral response included antibodies against secreted viral proteins. Many proteins were detected, with the primary band corresponding to a band of 28 or 30 kDa in cells infected with Dryvax or LC16m8, respectively. This was identified as the vaccinia virus complement protein (VCP), which migrated more slowly in LC16m8-infected cells due to post-translational glycosylation. Vaccinia virus deleted in VCP, vVCPko, protected mice from a lethal intranasal challenge of vaccinia Western Reserve strain. Mice vaccinated with purified VCP demonstrated a strong humoral response, but were not protected against a moderate lethal challenge of vaccinia virus, suggesting that the humoral response against VCP is not critical for protection.

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36

Hruby, D. E. "Vaccinia virus vectors: new strategies for producing recombinant vaccines." Clinical Microbiology Reviews 3, n. 2 (1990): 153–70. http://dx.doi.org/10.1128/cmr.3.2.153-170.1990.

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37

Tack, Danielle M., Kevin L. Karem, Jay R. Montgomery, Limone Collins, Marthe G. Bryant-Genevier, Rosemary Tiernan, Maria Cano et al. "Unintentional transfer of vaccinia virus associated with smallpox vaccines". Human Vaccines & Immunotherapeutics 9, n. 7 (9 aprile 2013): 1489–96. http://dx.doi.org/10.4161/hv.24319.

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38

Prideaux, Christopher T., Sharad Kumar e David B. Boyle. "Comparative analysis of vaccinia virus promoter activity in fowlpox and vaccinia virus recombinants". Virus Research 16, n. 1 (aprile 1990): 43–57. http://dx.doi.org/10.1016/0168-1702(90)90042-a.

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39

Chung, Che-Sheng, Chein-Hung Chen, Ming-Yi Ho, Cheng-Yen Huang, Chung-Lin Liao e Wen Chang. "Vaccinia Virus Proteome: Identification of Proteins in Vaccinia Virus Intracellular Mature Virion Particles". Journal of Virology 80, n. 5 (1 marzo 2006): 2127–40. http://dx.doi.org/10.1128/jvi.80.5.2127-2140.2006.

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ABSTRACT Vaccinia virus is a large enveloped poxvirus with more than 200 genes in its genome. Although many poxvirus genomes have been sequenced, knowledge of the host and viral protein components of the virions remains incomplete. In this study, we used gel-free liquid chromatography and tandem mass spectroscopy to identify the viral and host proteins in purified vaccinia intracellular mature virions (IMV). Analysis of the proteins in the IMV showed that it contains 75 viral proteins, including structural proteins, enzymes, transcription factors, and predicted viral proteins not known to be expressed or present in the IMV. We also determined the relative abundances of the individual protein components in the IMV. Finally, 23 IMV-associated host proteins were also identified. This study provides the first comprehensive structural analysis of the infectious vaccinia virus IMV.

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40

Leite, Juliana A., Betânia P. Drumond, Giliane S. Trindade, Zélia I. P. Lobato, Flávio G. da Fonseca, João R. dos Santos, Marieta C. Madureira et al. "Passatempo Virus, a Vaccinia Virus Strain, Brazil". Emerging Infectious Diseases 11, n. 12 (dicembre 2005): 1935–41. http://dx.doi.org/10.3201/eid1112.050773.

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41

Ramírez, Juan C., M. Magdalena Gherardi, Dolores Rodríguez e Mariano Esteban. "Attenuated Modified Vaccinia Virus Ankara Can Be Used as an Immunizing Agent under Conditions of Preexisting Immunity to the Vector". Journal of Virology 74, n. 16 (15 agosto 2000): 7651–55. http://dx.doi.org/10.1128/jvi.74.16.7651-7655.2000.

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ABSTRACT A problem associated with the use of vaccinia virus recombinants as vaccines is the existence of a large human population with preexisting immunity to the vector. Here we showed that after a booster with attenuated recombinant modified vaccinia virus Ankara (rMVA), higher humoral and cellular immune responses to foreign antigens (human immunodeficiency virus type 1 Env and β-galactosidase) were found in mice preimmunized with rMVA than in mice primed with the virulent Western Reserve strain and boosted with rMVA. This enhancement correlated with higher levels of expression of foreign antigens after the booster.

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42

Benning, Nicola, e Daniel E. Hassett. "Vaccinia Virus Infection during Murine Pregnancy: a New Pathogenesis Model for Vaccinia Fetalis". Journal of Virology 78, n. 6 (15 marzo 2004): 3133–39. http://dx.doi.org/10.1128/jvi.78.6.3133-3139.2004.

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ABSTRACT Vaccinia fetalis, the vertical transfer of vaccinia virus from mother to fetus, is a relatively rare but often fatal complication of primary vaccinia virus vaccination during pregnancy. To date there has been no attempt to develop an animal model to study the pathogenesis of this acute viral infection in vivo. Here we report that infection of gestating BALB/c mice by either intravenous or intraperitoneal routes with the Western Reserve strain of vaccinia virus results in the rapid colonization of the placenta and vertical transfer of virus to the developing fetus. Systemic maternal infections during gestation lead to the death of all offspring prior to or very shortly after birth. Using in situ hybridization for vaccinia virus mRNA to identify infected cells, we show that the virus initially colonizes cells lining maternal lacunae within the trophospongium layer of the placenta. The study of this model will significantly enhance our understanding of the pathogenesis of fetal vaccinia virus infections and aid in the development of effective treatments designed to reduce the risk of vaccinia virus-associated complications during pregnancy.

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43

Klote, Mary M., George V. Ludwig, Melanie P. Ulrich, Lisa A. Black, Dallas C. Hack, Renata J. M. Engler e Bryan L. Martin. "Absence of oropharyngeal vaccinia virus after vaccinia (smallpox) vaccination". Annals of Allergy, Asthma & Immunology 94, n. 6 (giugno 2005): 682–85. http://dx.doi.org/10.1016/s1081-1206(10)61328-2.

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44

O'Neil, B. H., Y. Kawakami, N. P. Restifo, J. R. Bennink, J. W. Yewdell e S. A. Rosenberg. "Detection of shared MHC-restricted human melanoma antigens after vaccinia virus-mediated transduction of genes coding for HLA." Journal of Immunology 151, n. 3 (1 agosto 1993): 1410–18. http://dx.doi.org/10.4049/jimmunol.151.3.1410.

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Abstract To detect shared human melanoma Ag that are recognized by HLA-A2 restricted, melanoma-specific CTL derived from tumor infiltrating lymphocytes, we have developed a convenient method to insert and express foreign HLA genes capable of presenting Ag on target cell lines. Seventeen melanoma cell lines and 11 nonmelanoma cell lines were infected with recombinant vaccinia virus containing the HLA-A2.1 gene. Infection by the vaccinia virus resulted in expression of functional HLA-A2 molecules on the cell surface of virtually 100% of infected cells within a 3.5-h period. The results showed that 11 of 17 (65%) naturally HLA-A2- melanoma cell lines were specifically lysed by the HLA-A2-restricted, melanoma-specific TIL after infection with the vaccinia-HLA-A2.1 virus. None of the nine human nonmelanoma cell lines tested (three colon cancer, four breast cancer, or two immortalized non-tumor cell lines) or two murine melanoma cell lines were lysed by the HLA-A2-restricted TIL after vaccinia-HLA-A2.1 infection. Coinfection of the vaccinia virus containing the beta 2-microglobulin gene with the vaccinia-HLA-A2.1 virus increased the surface expression of HLA-A2 and subsequent lysis by melanoma-specific tumor infiltrating lymphocytes. With this new method we could extend previous findings demonstrating that shared melanoma Ag recognized by HLA-A2-restricted tumor infiltrating lymphocytes exist among melanoma cells from different patients regardless of HLA type. These Ag represent excellent candidates for the development of vaccines to induce T cell responses for the immunotherapy of patients with melanoma.

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Chung, Che-Sheng, Jye-Chian Hsiao, Yuan-Shau Chang e Wen Chang. "A27L Protein Mediates Vaccinia Virus Interaction with Cell Surface Heparan Sulfate". Journal of Virology 72, n. 2 (1 febbraio 1998): 1577–85. http://dx.doi.org/10.1128/jvi.72.2.1577-1585.1998.

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ABSTRACT Vaccinia virus has a wide host range and infects mammalian cells of many different species. This suggests that the cell surface receptors for vaccinia virus are ubiquitously expressed and highly conserved. Alternatively, different receptors are used for vaccinia virus infection of different cell types. Here we report that vaccinia virus binds to heparan sulfate, a glycosaminoglycan (GAG) side chain of cell surface proteoglycans, during virus infection. Soluble heparin specifically inhibits vaccinia virus binding to cells, whereas other GAGs such as condroitin sulfate or dermantan sulfate have no effect. Heparin also blocks infections by cowpox virus, rabbitpox virus, myxoma virus, and Shope fibroma virus, suggesting that cell surface heparan sulfate could be a general mediator of the entry of poxviruses. The biochemical nature of the heparin-blocking effect was investigated. Heparin analogs that have acetyl groups instead of sulfate groups also abolish the inhibitory effect, suggesting that the negative charges on GAGs are important for virus infection. Furthermore, BSC40 cells treated with sodium chlorate to produce undersulfated GAGs are more refractory to vaccinia virus infection. Taken together, the data support the notion that cell surface heparan sulfate is important for vaccinia virus infection. Using heparin-Sepharose beads, we showed that vaccinia virus virions bind to heparin in vitro. In addition, we demonstrated that the recombinant A27L gene product binds to the heparin beads in vitro. This recombinant protein was further shown to bind to cells, and such interaction could be specifically inhibited by soluble heparin. All the data together indicated that A27L protein could be an attachment protein that mediates vaccinia virus binding to cell surface heparan sulfate during viral infection.

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46

Sutter, Gerd, e Caroline Staib. "Vaccinia Vectors as Candidate Vaccines: The Development of Modified Vaccinia Virus Ankara for Antigen Delivery". Current Drug Target -Infectious Disorders 3, n. 3 (1 settembre 2003): 263–71. http://dx.doi.org/10.2174/1568005033481123.

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47

Huang, Cheng-Yen, Tsai-Yi Lu, Chi-Horng Bair, Yuan-Shau Chang, Jeng-Kuan Jwo e Wen Chang. "A Novel Cellular Protein, VPEF, Facilitates Vaccinia Virus Penetration into HeLa Cells through Fluid Phase Endocytosis". Journal of Virology 82, n. 16 (11 giugno 2008): 7988–99. http://dx.doi.org/10.1128/jvi.00894-08.

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ABSTRACT 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 the cell through an endocytic route that required a dynamin-mediated pathway but not a clathrin- or caveola-mediated pathway. Moreover, virus penetration required a novel cellular protein, vaccinia virus penetration factor (VPEF). VPEF was detected on cell surface lipid rafts and on vesicle-like structures in the cytoplasm. Both vaccinia virus and dextran transiently colocalized with VPEF, and, importantly, knockdown of VPEF expression blocked vaccinia virus penetration as well as intracellular transport of dextran, suggesting that VPEF mediates vaccinia virus entry through a fluid uptake endocytosis process in HeLa cells. Intracellular VPEF-containing vesicles did not colocalize with Rab5a or caveolin but partially colocalized with Rab11, supporting the idea that VPEF plays a role in vesicle trafficking and recycling in HeLa cells. In summary, this study characterized the mechanism by which vaccinia virus enters HeLa cells and identified a cellular factor, VPEF, that is exploited by vaccinia virus for cell entry through fluid phase endocytosis.

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48

Moses, Phyllis B. "Vaccinia Virus: Reinventing the Wheel". BioScience 36, n. 3 (marzo 1986): 148–50. http://dx.doi.org/10.2307/1310299.

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Assis, Felipe Lopes, Iara Apolinario Borges, Paulo César Peregrino Ferreira, Cláudio Antônio Bonjardim, Giliane de Souza Trindade, Zélia Inês Portela Lobato, Maria Isabel Maldonado Guedes, Vaz Mesquita, Erna Geessien Kroon e Jônatas Santos Abrahão. "Group 2 Vaccinia Virus, Brazil". Emerging Infectious Diseases 18, n. 12 (dicembre 2012): 2035–38. http://dx.doi.org/10.3201/eid1812.120145.

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50

Moss, B. "Regulation of Vaccinia Virus Transcription". Annual Review of Biochemistry 59, n. 1 (giugno 1990): 661–88. http://dx.doi.org/10.1146/annurev.bi.59.070190.003305.

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