Modified Vaccinia Ankara Virus

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Modified Vaccinia Ankara Virus
Systematics
Classification : Viruses
Area : Varidnaviria
Empire : Bamfordvirae
Phylum : Nucleocytoviricota
Class : Pokkesviricetes
Order : Chitovirals
Family : Poxviridae
Subfamily : Chordopoxvirinae
Genre : Orthopoxvirus
Type : Vaccinia virus
Subspecies : Modified Vaccinia Ankara Virus
Taxonomic characteristics
Genome : dsDNA linear
Baltimore : Group 1
Symmetry : complex
Cover : available
Scientific name
Modified Vaccinia Ankara virus
Short name
MVA
Left
NCBI  Taxonomy: 467144
ICTV Taxon History: 201854775 (species)

The modified vaccinia ankara (MVA) is an attenuated pox virus , which for vaccine purposes is used.

Emergence

In the course of its original generation by passengers (serial infections of cell cultures ) in chicken embryo fibroblast cells (CEF, 'chicken embryo fibroblasts '), MVA lost over 10% of its genes compared to the Copenhagen vaccinia virus (with 192 kilobase pairs ). This also includes genes that enable replication in mammalian cells, which is why MVA is replication-incompetent in humans or the mammalian cells are non-permissive . MVA can be replicated in CEF cells. A variant of the MVA was developed which shows the progress of the recombination by changing colors with fluorescent reporter proteins (green, colorless, red).

Genome

The DNA - the genome of the MVA consists of 178 kilobase pairs with 177 open reading frames . In cell cultures, genes for immune evasion tend to be less important than in organisms with an immune system , which is why some areas with genes for immune evasion are missing compared to the Copenhagen vaccinia virus.

Applications

Modified Vaccinia Ankara Virus was developed as a smallpox vaccine and is used experimentally as a viral vector for vaccination against other diseases, e.g. B. HIV . For this purpose, genes from antigens are inserted into the genome of the MVA by homologous recombination .

In animal experiments , depending on the antigen contained , transgenic MVA showed an immune reaction against HIV, parainfluenza virus , influenza virus , hepatitis C virus , cytomegalovirus , MERS coronavirus , measles virus , flavivirus , Plasmodium falciparum , tuberculosis or various types of cancer . This produces antibodies and T cells against the antigen. Like all vectors based on smallpox viruses, MVA can only be used once per vaccinee, since the antibodies and T cells that are also produced against MVA proteins, if used again on the same vaccinee, lead to premature degradation of the MVA vaccine or excessive immune reactions to it can lead. Therefore, transgenic MVA are not used in people who have previously received a smallpox vaccination. Because it is used only once per person to be vaccinated, it is sometimes used either as a prime (initial immunization) or as a boost (repeat immunization) . In vaccination with vectors based on avipox contrast, no anti-vector antibodies arise.

The Modified Vaccinia Ankara Virus is in various phase I / II clinical trials . Among other things, it is being carried out by IAVI as a vaccine against HIV with antigens of HIV in various phase I clinical studies (MVA-B).

history

The modified vaccinia Ankara virus was developed by Anton Mayr in 1975 as a smallpox vaccine through over 570 passages in embryonic chicken cell cultures. The underlying vaccinia virus Ankara had previously been passaged in calves and donkeys. MVA was applied to over 120,000 people in Bavaria from 1977 in the course of the eradication of human smallpox viruses through intradermal , subcutaneous or intramuscular injections . The use as a vaccination vector with few side effects against other diseases was developed in 1992 in the research group of Bernard Moss .

Individual evidence

  1. ↑ a b c d e ICTV: ICTV Taxonomy history: Variola virus , EC 51, Berlin, Germany, July 2019; Email ratification March 2020 (MSL # 35)
  2. ↑ JS Kennedy, RN Greenberg: IMVAMUNE: modified vaccinia Ankara strain as an attenuated smallpox vaccine. In: Expert review of vaccines. Volume 8, number 1, January 2009, pp. 13-24, doi : 10.1586 / 14760584.8.1.13 , PMID 19093767 .
  3. ↑ J. Parrino, LH McCurdy, BD Larkin, IJ Gordon, SE Rucker, ME Enama, RA Koup, M. Roederer, RT Bailer, Z. Moodie, L. Gu, L. Yan, BS Graham: Safety, immunogenicity and efficacy of modified vaccinia Ankara (MVA) against Dryvax challenge in vaccinia-naïve and vaccinia-immune individuals. In: Vaccine. Volume 25, Number 8, February 2007, pp. 1513-1525, doi : 10.1016 / j.vaccine.2006.10.047 , PMID 17126963 , PMC 1892755 (free full text).
  4. ^ A b G. Antoine, F. Scheiflinger, F. Dorner, FG Falkner: The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses. In: Virology. Volume 244, Number 2, May 1998, pp. 365-396, doi : 10.1006 / viro.1998.9123 , PMID 9601507 .
  5. ↑ G. Di Lullo, E. Soprana, M. Panigada, A. Palini, Volker Erfle, C. Staib, G. Sutter, AG Siccardi: Marker gene swapping facilitates recombinant Modified Vaccinia Virus Ankara production by host-range selection. In: Journal of virological methods. Volume 156, number 1-2, March 2009, pp. 37-43, doi : 10.1016 / j.jviromet.2008.10.026 , PMID 19038289 .
  6. ^ A b E. Soprana, M. Panigada, M. Knauf, A. Radaelli, L. Vigevani, A. Palini, C. Villa, M. Malnati, G. Cassina, Reinhard Kurth , S. Norley, AG Siccardi : Joint Production of prime / boost pairs of Fowlpox Virus and Modified Vaccinia Ankara recombinants carrying the same transgene. In: Journal of virological methods. Volume 174, number 1-2, June 2011, pp. 22-28, doi : 10.1016 / j.jviromet.2011.03.013 , PMID 21419167 .
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  10. ^ F. Song, R. Fux, LB Provacia, A. Volz, M. Eickmann, S. Becker, AD Osterhaus, BL Haagmans, G. Sutter: Middle East respiratory syndrome coronavirus spike protein delivered by modified vaccinia virus Ankara efficiently induces virus -neutralizing antibodies. In: Journal of virology. Volume 87, number 21, November 2013, pp. 11950–11954, doi : 10.1128 / JVI.01672-13 , PMID 23986586 , PMC 3807317 (free full text).
  11. ^ SC Gilbert, VS Moorthy, L. Andrews, AA Pathan, SJ McConkey, JM Vuola, SM Keating, T. Berthoud, D. Webster, H. McShane, AV Hill: Synergistic DNA-MVA prime-boost vaccination regimes for malaria and tuberculosis. In: Vaccine. Volume 24, Number 21, May 2006, pp. 4554-4561, doi : 10.1016 / j.vaccine.2005.08.048 , PMID 16150517 .
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  15. ↑ CE Gómez, B. Perdiguero, J. García-Arriaza, M. Esteban: Clinical applications of attenuated MVA poxvirus strain. In: Expert review of vaccines. Volume 12, number 12, December 2013, pp. 1395-1416, doi : 10.1586 / 14760584.2013.845531 , PMID 24168097 .
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  17. ↑ A. Mayr, V. Hochstein-Mintzel, H. Stickl: Origin, properties and use of the attenuated Vaccinia strain MVA. In: Infection (1975), Volume 3: p. 9.
  18. ^ LH McCurdy, BD Larkin, JE Martin, BS Graham: Modified vaccinia Ankara: potential as an alternative smallpox vaccine. In: Clinical Infectious Diseases . Volume 38, Number 12, June 2004, pp. 1749-1753, doi : 10.1086 / 421266 , PMID 15227622 .
  19. ^ G. Sutter, B. Moss: Nonreplicating vaccinia vector efficiently expresses recombinant genes. In: Proceedings of the National Academy of Sciences . Volume 89, Number 22, November 1992, pp. 10847-10851, PMID 1438287 , PMC 50439 (free full text).