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Archives of virology2009; 154(5); 867-873; doi: 10.1007/s00705-009-0378-9

In vivo evolution of the gp90 gene and consistently low plasma viral load during transient immune suppression demonstrate the safety of an attenuated equine infectious anemia virus (EIAV) vaccine.

Abstract: To study the in vivo evolution of the attenuated Chinese equine infectious anemia virus (EIAV) vaccine, viral gp90 gene variation and virus replication in immunosuppressed hosts were investigated. The results showed that after vaccination, the gp90 gene followed an evolutionary trend of declining diversity. The trend coincided with the maturation of immunity to EIAV, and eventually, the gp90 gene became highly homologous. The sequences of these predominant quasispecies were consistently detected up to 18 months after vaccination. Furthermore, after transient immune suppression with dexamethasone, the plasma viral RNA copy number of the vaccine strain in three vaccinated ponies remained consistently below the "pathogenic threshold" level, while the viral load increased by 25,000-fold in the positive control of an inapparent carrier of the parental virulent strain. This study is the first to provide evidence for the safety of an attenuated lentiviral vaccine with decreased genomic diversity and consistently low viral replication under suppressed immunity.
Publication Date: 2009-04-12 PubMed ID: 19363668DOI: 10.1007/s00705-009-0378-9Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study investigates the in vivo evolution of the Chinese equine infectious anemia virus (EIAV) vaccine, observing a decrease in diversity of the viral gp90 gene over time and consistently low levels of virus replication, even with suppressed immunity. It provides evidence supporting the safety of this weakened lentiviral vaccine.

Viral gp90 Gene Variation and Vaccine Evolution

  • The study focused on the evolution of the gp90 gene of the attenuated EIAV vaccine in the body (in vivo).
  • The gp90 gene of the EIAV vaccine showed a decreased diversity over time after vaccination.
  • The declining diversity of the gp90 gene is reported to align with the maturation of immunity against EIAV, implying the adaptability of the vaccine to the host’s immune system.
  • With the progression of time, the gp90 gene showed a high level of homology or similarity. The sequences of these predominant quasi species (viral forms within a host) were consistently detected for up to 18 months post-vaccination.

Viral Replication under Immune Suppression

  • To test the safety of the vaccine under immune suppression, dexamethasone, an immune suppressant, was administered to the vaccinated horses.
  • Unlike a virulent strain of the virus, which showed a 25,000-fold increase in viral load in a host with suppressed immunity, the vaccine strain maintained viral RNA copy number in the plasma consistently below the “pathogenic threshold,” even under immune suppression.
  • This demonstrated that the vaccine was still functional and safe, keeping the viral replication under control even when the host’s immune response was compromised.

Implications of the Study

  • This study provides the first piece of evidence attesting to the safety of this attenuated EIAV vaccine.
  • It highlights the low-risk nature of the vaccine not just in normal conditions, but also under immunosuppression.
  • The consistent low viral load throughout immune suppression indicates the vaccine’s effectiveness at containing the virus, thereby demonstrating its potential as a protective measure against EIAV.
  • Moreover, the findings regarding the in vivo evolution of the gp90 gene contribute to our understanding of how attenuated vaccines function and evolve within the host.

Cite This Article

APA
Ma J, Jiang C, Lin Y, Wang X, Zhao L, Xiang W, Shao Y, Shen R, Kong X, Zhou J. (2009). In vivo evolution of the gp90 gene and consistently low plasma viral load during transient immune suppression demonstrate the safety of an attenuated equine infectious anemia virus (EIAV) vaccine. Arch Virol, 154(5), 867-873. https://doi.org/10.1007/s00705-009-0378-9

Publication

ISSN: 1432-8798
NlmUniqueID: 7506870
Country: Austria
Language: English
Volume: 154
Issue: 5
Pages: 867-873

Researcher Affiliations

Ma, Jian
  • State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China.
Jiang, Chenggang
    Lin, Yuezhi
      Wang, Xuefeng
        Zhao, Liping
          Xiang, Wenhua
            Shao, Yiming
              Shen, Rongxian
                Kong, Xiangang
                  Zhou, Jianhua

                    MeSH Terms

                    • Animals
                    • Equine Infectious Anemia / immunology
                    • Equine Infectious Anemia / prevention & control
                    • Genes, Viral
                    • Glycoproteins / genetics
                    • Horses / virology
                    • Immunosuppression Therapy
                    • Infectious Anemia Virus, Equine / genetics
                    • Infectious Anemia Virus, Equine / immunology
                    • Infectious Anemia Virus, Equine / physiology
                    • Mutation
                    • Phylogeny
                    • RNA, Viral / genetics
                    • Vaccines, Attenuated / immunology
                    • Viral Envelope Proteins / genetics
                    • Viral Load
                    • Viral Vaccines / immunology
                    • Virus Replication

                    Citations

                    This article has been cited 7 times.
                    1. Wang HN, Rao D, Fu XQ, Hu MM, Dong JG. Equine infectious anemia virus in China. Oncotarget 2018 Jan 2;9(1):1356-1364.
                      doi: 10.18632/oncotarget.20381pubmed: 29416700google scholar: lookup
                    2. Han X, Zhang P, Yu W, Xiang W, Li X. Amino acid mutations in the env gp90 protein that modify N-linked glycosylation of the Chinese EIAV vaccine strain enhance resistance to neutralizing antibodies. Virus Genes 2016 Dec;52(6):814-822.
                      doi: 10.1007/s11262-016-1382-2pubmed: 27572122google scholar: lookup
                    3. Liu Q, Ma J, Wang XF, Xiao F, Li LJ, Zhang JE, Lin YZ, Du C, He XJ, Wang X, Zhou JH. Infection with equine infectious anemia virus vaccine strain EIAVDLV121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response. Vet Immunol Immunopathol 2016 Feb;170:30-40.
                      doi: 10.1016/j.vetimm.2016.01.006pubmed: 26832985google scholar: lookup
                    4. Ma J, Wang SS, Lin YZ, Liu HF, Liu Q, Wei HM, Wang XF, Wang YH, Du C, Kong XG, Zhou JH, Wang X. Infection of equine monocyte-derived macrophages with an attenuated equine infectious anemia virus (EIAV) strain induces a strong resistance to the infection by a virulent EIAV strain. Vet Res 2014 Aug 9;45(1):82.
                      doi: 10.1186/s13567-014-0082-ypubmed: 25106750google scholar: lookup
                    5. Reina R, de Andrés D, Amorena B. Immunization against small ruminant lentiviruses. Viruses 2013 Aug 2;5(8):1948-63.
                      doi: 10.3390/v5081948pubmed: 23917352google scholar: lookup
                    6. Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Wang F, Shen R, Zhou J. Unique evolution characteristics of the envelope protein of EIAV(LN₄₀), a virulent strain of equine infectious anemia virus. Virus Genes 2011 Apr;42(2):220-8.
                      doi: 10.1007/s11262-010-0563-7pubmed: 21369830google scholar: lookup
                    7. Qi X, Wang X, Wang S, Lin Y, Jiang C, Ma J, Zhao L, Lv X, Shen R, Wang F, Kong X, Su Z, Zhou J. Genomic analysis of an effective lentiviral vaccine-attenuated equine infectious anemia virus vaccine EIAV FDDV13. Virus Genes 2010 Aug;41(1):86-98.
                      doi: 10.1007/s11262-010-0491-6pubmed: 20526660google scholar: lookup