Envelope determinants of equine lentiviral vaccine protection.
Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be dete...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3682429?pdf=render |
| _version_ | 1811206041820463104 |
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| author | Jodi K Craigo Corin Ezzelarab Sheila J Cook Liu Chong David Horohov Charles J Issel Ronald C Montelaro |
| author_facet | Jodi K Craigo Corin Ezzelarab Sheila J Cook Liu Chong David Horohov Charles J Issel Ronald C Montelaro |
| author_sort | Jodi K Craigo |
| collection | DOAJ |
| description | Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. |
| first_indexed | 2024-04-12T03:41:08Z |
| format | Article |
| id | doaj.art-80877b18412448dc8b050d12a9fbc57d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T03:41:08Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-80877b18412448dc8b050d12a9fbc57d2022-12-22T03:49:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6609310.1371/journal.pone.0066093Envelope determinants of equine lentiviral vaccine protection.Jodi K CraigoCorin EzzelarabSheila J CookLiu ChongDavid HorohovCharles J IsselRonald C MontelaroLentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection.http://europepmc.org/articles/PMC3682429?pdf=render |
| spellingShingle | Jodi K Craigo Corin Ezzelarab Sheila J Cook Liu Chong David Horohov Charles J Issel Ronald C Montelaro Envelope determinants of equine lentiviral vaccine protection. PLoS ONE |
| title | Envelope determinants of equine lentiviral vaccine protection. |
| title_full | Envelope determinants of equine lentiviral vaccine protection. |
| title_fullStr | Envelope determinants of equine lentiviral vaccine protection. |
| title_full_unstemmed | Envelope determinants of equine lentiviral vaccine protection. |
| title_short | Envelope determinants of equine lentiviral vaccine protection. |
| title_sort | envelope determinants of equine lentiviral vaccine protection |
| url | http://europepmc.org/articles/PMC3682429?pdf=render |
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