Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Protective Efficacy of Centralized and Polyvalent Envelope Immunogens in an Attenuated Equine Lentivirus Vaccine

Craigo, JK and Ezzelarab, C and Cook, SJ and Liu, C and Horohov, D and Issel, CJ and Montelaro, RC (2015) Protective Efficacy of Centralized and Polyvalent Envelope Immunogens in an Attenuated Equine Lentivirus Vaccine. PLoS Pathogens, 11 (1). 1 - 14. ISSN 1553-7366

[img]
Preview
PDF
Published Version
Available under License : See the attached license file.

Download (2MB)
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

© 2015 Craigo et al. Lentiviral Envelope (Env) antigenic variation and related immune evasion present major hurdles to effective vaccine development. Centralized Env immunogens that minimize the genetic distance between vaccine proteins and circulating viral isolates are an area of increasing study in HIV vaccinology. To date, the efficacy of centralized immunogens has not been evaluated in the context of an animal model that could provide both immunogenicity and protective efficacy data. We previously reported on a live-attenuated (attenuated) equine infectious anemia (EIAV) virus vaccine, which provides 100% protection from disease after virulent, homologous, virus challenge. Further, protective efficacy demonstrated a significant, inverse, linear relationship between EIAV Env divergence and protection from disease when vaccinates were challenged with viral strains of increasing Env divergence from the vaccine strain Env. Here, we sought to comprehensively examine the protective efficacy of centralized immunogens in our attenuated vaccine platform. We developed, constructed, and extensively tested a consensus Env, which in a virulent proviral backbone generated a fully replication-competent pathogenic virus, and compared this consensus Env to an ancestral Env in our attenuated proviral backbone. A polyvalent attenuated vaccine was established for comparison to the centralized vaccines. Additionally, an engineered quasispecies challenge model was created for rigorous assessment of protective efficacy. Twenty-four EIAV-naïve animals were vaccinated and challenged along with six-control animals six months post-second inoculation. Pre-challenge data indicated the consensus Env was more broadly immunogenic than the Env of the other attenuated vaccines. However, challenge data demonstrated a significant increase in protective efficacy of the polyvalent vaccine. These findings reveal, for the first time, a consensus Env immunogen that generated a fully-functional, replication-competent lentivirus, which when experimentally evaluated, demonstrated broader immunogenicity that does not equate to higher protective efficacy.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Craigo, JK
Ezzelarab, C
Cook, SJ
Liu, Cchl139@pitt.eduCHL139
Horohov, D
Issel, CJ
Montelaro, RCrmont@pitt.eduRMONT
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorSwanstrom, RonaldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, or Units > Center for Vaccine Research
Date: 1 January 2015
Date Type: Publication
Journal or Publication Title: PLoS Pathogens
Volume: 11
Number: 1
Page Range: 1 - 14
DOI or Unique Handle: 10.1371/journal.ppat.1004610
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
ISSN: 1553-7366
Other ID: NLM PMC4287611
PubMed Central ID: PMC4287611
PubMed ID: 25569288
Date Deposited: 12 May 2015 19:41
Last Modified: 29 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/24080

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com


Actions (login required)

View Item View Item