Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines.
Abstract: We previously reported that an experimental live-attenuated equine infectious anemia virus (EIAV) vaccine, containing a mutated S2 accessory gene, provided protection from disease and detectable infection after virulent virus (EIAV(PV)) challenge [Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, et al. A live-attenuated equine infectious anemia virus proviral vaccine with a modified S2 gene provides protection from detectable infection by intravenous virulent virus challenge of experimentally inoculated horses. J Virol 2003;77(13):7244-53; Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, et al. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy. J Virol 2005;79(5):2666-77]. To determine if attenuated EIAV vaccines actually prevent persistent infection by challenge virus, we employed a 14-day dexamethasone treatment of vaccinated horses post-challenge to suppress host immunity and amplify replication levels of any infecting EIAV. At 2 months post-challenge the horses were all protected from virulent-virus challenge, evidenced by a lack of EIA signs and detectable challenge plasma viral RNA. Upon immune suppression, 6/12 horses displayed clinical EIA. Post-immune suppression characterizations demonstrated that the attenuated vaccine evidently prevented detectable challenge virus infection in 50% of horses. These data highlight the utility of post-challenge immune suppression for evaluating persistent viral vaccine protective efficacy.
Publication Date: 2006-09-22 PubMed ID: 17023099PubMed Central: PMC1855206DOI: 10.1016/j.vaccine.2006.09.040Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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The research paper primarily discusses an investigation conducted to determine the effectiveness of attenuated equine infectious anemia virus (EIAV) vaccines in preventing persistent infection. Through the implementation of 14-day immune suppression post-vaccination challenge, the team monitored the increase in EIAV replication in vaccinated horses to assess the vaccine’s protective efficacy.
Study Background
- The researchers had previously reported the development of a live-attenuated equine infectious anemia virus (EIAV) vaccine. This vaccine, which features a mutated S2 accessory gene, displayed protection from disease and noticeable infection after being challenged with a virulent version of the virus (EIAV(PV)).
Objective of the Current Study
- In this study, the researchers sought to ascertain whether the attenuated EIAV vaccines do indeed prevent ongoing infection by the challenge virus. To achieve this, the participant horses that had been vaccinated were subjected to a 14-day dexamethasone treatment post-challenge. This was done to suppress the host horses’ immunity and increase the replication levels of any infecting EIAV.
Detailed Findings
- At 2 months post-challenge, all the horses were seen to be protected from virulent-virus challenge. This finding was evidenced by the complete absence of Equine Infectious Anemia (EIA) signs and detectable challenge plasma viral RNA.
- Post-immune suppression, however, displayed a different scenario, wherein six out of the twelve horses displayed clinical EIA symptoms. This suggested that the immune-suppressed horses were not able to completely prevent the infection.
- The characterizations conducted post-immune suppression indicated that the attenuated vaccine prevented detectable challenge virus infection in 50% of the horses. This, however, means that the other half of the horses still became infected despite being vaccinated.
Insights Gained
- Based on the results, the researchers concluded that the steps taken, specifically the post-challenge immune suppression, have demonstrated their utility in assessing the persistent viral vaccine protective efficacy. This novel technique provides a rigorous assessment of the vaccine’s ability to protect against infections, emphasizing the importance of not just the vaccine itself, but also the host’s immune system, in ensuring full protection.
Cite This Article
APA
Craigo JK, Durkin S, Sturgeon TJ, Tagmyer T, Cook SJ, Issel CJ, Montelaro RC.
(2006).
Immune suppression of challenged vaccinates as a rigorous assessment of sterile protection by lentiviral vaccines.
Vaccine, 25(5), 834-845.
https://doi.org/10.1016/j.vaccine.2006.09.040 Publication
Researcher Affiliations
- Department of Molecular Genetics and Biochemistry, W1144 Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States.
MeSH Terms
- Adjuvants, Immunologic / pharmacology
- Amino Acid Sequence
- Animals
- Antibodies, Viral / blood
- Base Sequence
- Dexamethasone / pharmacology
- Equine Infectious Anemia / prevention & control
- Female
- Horses
- Infectious Anemia Virus, Equine / immunology
- Male
- Molecular Sequence Data
- RNA, Viral / blood
- Reverse Transcriptase Polymerase Chain Reaction
- T-Lymphocytes, Cytotoxic / immunology
- Vaccination
- Vaccines, Attenuated
- Viral Vaccines / immunology
Grant Funding
- R01 AI025850 / NIAID NIH HHS
- R01 AI25850 / NIAID NIH HHS
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Citations
This article has been cited 14 times.- de Pablo-Maiso L, Doménech A, Echeverría I, Gómez-Arrebola C, de Andrés D, Rosati S, Gómez-Lucia E, Reina R. Prospects in Innate Immune Responses as Potential Control Strategies against Non-Primate Lentiviruses. Viruses 2018 Aug 17;10(8).
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