scholarly journals Envelope-specific T-helper and cytotoxic T-lymphocyte responses associated with protective immunity to equine infectious anemia virus

2007 ◽  
Vol 88 (4) ◽  
pp. 1324-1336 ◽  
Author(s):  
Tara L. Tagmyer ◽  
Jodi K. Craigo ◽  
Sheila J. Cook ◽  
Charles J. Issel ◽  
Ronald C. Montelaro
Keyword(s):  
Protective Immunity ◽  
Equine Infectious Anemia Virus ◽  
Cytotoxic T Lymphocyte ◽  
Asymptomatic Carrier ◽  
Cytotoxic T Cell ◽  
T Helper ◽  
Equine Infectious Anemia ◽  
Env Protein ◽  
Anemia Virus ◽  
Vaccine Immunity

Equine infectious anemia virus (EIAV) infection of horses provides a valuable model for examining the natural immunological control of lentivirus infection and disease and the mechanisms of protective and enhancing vaccine immunity. We have previously hypothesized that the EIAV envelope (Env) proteins gp90 and gp45 are major determinants of vaccine efficacy, and that the development of protective immunity by attenuated viral vaccines may be associated with the progressive redirection of immune responses from immunodominant, variable Env segments to immunorecessive, conserved Env sequences. Whilst the antibody-neutralization determinants of Env have been defined, there are to date no comprehensive analyses of the lymphoproliferative (T-helper, Th) and cytotoxic T-cell (CTL) epitopes of the EIAV Env proteins. Thus, in the current study, synthetic-peptide methodologies were used to define regions of EIAV Env associated with protective vaccine immunity in a panel of 12 horses inoculated with the attenuated EIAVD9 vaccine and two asymptomatic carrier horses infected experimentally with the virulent EIAVPV strain expressing the same Env protein as the vaccine strain. The results of these studies identified 17 broadly reactive Th peptides and six broadly reactive CTL peptides in the Env proteins of EIAV that were associated with protective immunity. Thus, these data provide for the first time a comprehensive mapping of EIAV Env-specific cellular regions that can be used to examine the development of protective immunity and to evaluate potential cellular immune determinants of protective immunity.

scholarly journals 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

2003 ◽  
Vol 77 (13) ◽  
pp. 7244-7253 ◽  
Author(s):  
Feng Li ◽  
Jodi K. Craigo ◽  
Laryssa Howe ◽  
Jonathan D. Steckbeck ◽  
Sheila Cook ◽  
...  
Keyword(s):  
Immune Responses ◽  
Equine Infectious Anemia Virus ◽  
High Dose ◽  
Accessory Gene ◽  
Virus Challenge ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Vaccine Immunity

ABSTRACT Previous evaluations of inactivated whole-virus and envelope subunit vaccines to equine infectious anemia virus (EIAV) have revealed a broad spectrum of efficacy ranging from highly type-specific protection to severe enhancement of viral replication and disease in experimentally immunized equids. Among experimental animal lentivirus vaccines, immunizations with live attenuated viral strains have proven most effective, but the vaccine efficacy has been shown to be highly dependent on the nature and severity of the vaccine virus attenuation. We describe here for the first time the characterization of an experimental attenuated proviral vaccine, EIAVUKΔS2, based on inactivation of the S2 accessory gene to down regulate in vivo replication without affecting in vitro growth properties. The results of these studies demonstrated that immunization with EIAVUKΔS2 elicited mature virus-specific immune responses by 6 months and that this vaccine immunity provided protection from disease and detectable infection by intravenous challenge with a reference virulent biological clone, EIAVPV. This level of protection was observed in each of the six experimental horses challenged with the reference virulent EIAVPV by using a low-dose multiple-exposure protocol (three administrations of 10 median horse infectious doses [HID50], intravenous) designed to mimic field exposures and in all three experimentally immunized ponies challenged intravenously with a single inoculation of 3,000 HID50. In contrast, naïve equids subjected to the low- or high-dose challenge develop a detectable infection of challenge virus and acute disease within several weeks. Thus, these data demonstrate that the EIAV S2 gene provides an optimal site for modification to achieve the necessary balance between attenuation to suppress virulence and replication potential to sufficiently drive host immune responses to produce vaccine immunity to viral exposure.

Cytotoxic T lymphocytes in protection against equine infectious anemia virus

2004 ◽  
Vol 5 (2) ◽  
pp. 271-276 ◽  
Author(s):  
Travis C. McGuire ◽  
Darrilyn G. Fraser ◽  
Robert H. Mealey
Keyword(s):  
T Lymphocytes ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocytes ◽  
Equine Infectious Anemia Virus ◽  
Neutralizing Antibody ◽  
Target Cells ◽  
T Helper ◽  
Immunodeficiency Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus

AbstractCytotoxic T lymphocytes (CTL) are associated with virus control in horses infected with equine infectious anemia virus (EIAV). Early in infection, control of the initial viremia coincides with the appearance of CTL and occurs before the appearance of neutralizing antibody. In carrier horses, treatment with immunosuppressive drugs results in viremia before a change in serum neutralizing antibody occurs. Clearance of initial viremia caused by other lentiviruses, including human immunodeficiency virus-1 and simian immunodeficiency virus, is also associated with CTL and not neutralizing antibody. In addition, depletion of CD8+cells prior to infection of rhesus monkeys with simian immunodeficiency prevents clearance of virus and the same treatment of persistently infected monkeys results in viremia. Cats given adoptive transfers of lymphocytes from vaccinated cats were protected and the protection was MHC-restricted, occurred in the absence of antiviral humoral immunity, and correlated with the transfer of cells with feline immunodeficiency virus-specific CTL and T-helper lymphocyte activities. Therefore, a lentiviral vaccine, including one for EIAV, needs to induce CTL. Based on initial failures to induce CTL to EIAV proteins by any means other than infection, we attempted to define an experimental system for the evaluation of methods for CTL induction. CTL epitopes restricted by the ELA-A1 haplotype were identified and the MHC class I molecule presenting these peptides was identified. This was done by expressing individual MHC class I molecules from cDNA clones in target cells. The target cells were then pulsed with peptides and used with effector CTL stimulated with the same peptides. In a preliminary experiment, immunization of three ELA-A1 haplotype horses with an Env peptide restricted by this haplotype resulted in CTL in peripheral blood mononuclear cells (PBMC) which recognized the Env peptide and virus-infected cells, but the CTL response was transient. Nevertheless there was significant protection against clinical disease following EIAV challenge of these immunized horses when compared with three control horses given the same virus challenge. These data indicated that responses to peptides in immunized horses needed to be enhanced. Optimal CTL responses require help from CD4+T lymphocytes, and experiments were done to identify EIAV peptides which stimulated CD4+T lymphocytes in PBMC from infected horses with different MHC class II types. Two broadly cross-reactive Gag peptides were identified which stimulated only an interferon γ response by CD4+T lymphocytes, which indicated a T helper 1 response is needed for CTL stimulation. Such peptides should facilitate CTL responses; however, other problems in inducing protection against lentiviruses remain, the most significant of them being EIAV variants that can escape both CTL and neutralizing antibody. A possible solution to CTL escape variants is the induction of high-avidity CTL to multiple EIAV epitopes.

scholarly journals Gag Protein Epitopes Recognized by CD4+T-Helper Lymphocytes from Equine Infectious Anemia Virus-Infected Carrier Horses

1999 ◽  
Vol 73 (5) ◽  
pp. 4257-4265 ◽  
Author(s):  
S. M. Lonning ◽  
W. Zhang ◽  
T. C. McGuire
Keyword(s):  
Equine Infectious Anemia Virus ◽  
Mononuclear Cells ◽  
Sequence Similarity ◽  
Peptide Vaccine ◽  
T Helper ◽  
Gag Protein ◽  
Immunodeficiency Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Th Lymphocytes

ABSTRACT Antigen-specific T-helper (Th) lymphocytes are critical for the development of antiviral humoral responses and the expansion of cytotoxic T lymphocytes (CTL). Identification of relevant Th lymphocyte epitopes remains an important step in the development of an efficacious subunit peptide vaccine against equine infectious anemia virus (EIAV), a naturally occurring lentivirus of horses. This study describes Th lymphocyte reactivity in EIAV carrier horses to two proteins, p26 and p15, encoded by the relatively conserved EIAV gag gene. Using partially overlapping peptides, multideterminant and possibly promiscuous epitopes were identified within p26. One peptide was identified which reacted with peripheral blood mononuclear cells (PBMC) from all five EIAV-infected horses, and three other peptides were identified which reacted with PBMC from four of five EIAV-infected horses. Four additional peptides containing both CTL and Th lymphocyte epitopes were also identified. Multiple epitopes were recognized in a region corresponding to the major homology region of the human immunodeficiency virus, a region with significant sequence similarity to other lentiviruses including simian immunodeficiency virus, puma lentivirus, feline immunodeficiency virus, Jembrana disease virus, visna virus, and caprine arthritis encephalitis virus. PBMC reactivity to p15 peptides from EIAV carrier horses also occurred. Multiple p15 peptides were shown to be reactive, but not all infected horses had Th lymphocytes recognizing p15 epitopes. The identification of peptides reactive with PBMC from outbred horses, some of which encoded both CTL and Th lymphocyte epitopes, should contribute to the design of synthetic peptide or recombinant vector vaccines for EIAV.

scholarly journals Envelope Determinants of Equine Infectious Anemia Virus Vaccine Protection and the Effects of Sequence Variation on Immune Recognition

2008 ◽  
Vol 82 (8) ◽  
pp. 4052-4063 ◽  
Author(s):  
Tara L. Tagmyer ◽  
Jodi K. Craigo ◽  
Sheila J. Cook ◽  
Deborah L. Even ◽  
Charles J. Issel ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Equine Infectious Anemia Virus ◽  
Immune Recognition ◽  
Vaccine Protection ◽  
Challenge Strain ◽  
Cellular Immune Responses ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Cellular Immune

ABSTRACT A highly effective attenuated equine infectious anemia virus (EIAV) vaccine (EIAVD9) capable of protecting 100% of horses from disease induced by a homologous Env challenge strain (EIAVPV) was recently tested in ponies to determine the level of protection against divergent Env challenge strains (J. K. Craigo, B. S. Zhang, S. Barnes, T. L. Tagmyer, S. J. Cook, C. J. Issel, and R. C. Montelaro, Proc. Natl. Acad. Sci. USA 104:15105-15110, 2007). An inverse correlation between challenge strain Env variation and vaccine protection from disease was observed. Given the striking differences in protective immunity, we hypothesized that analysis of the humoral and cellular immune responses to the Env protein could reveal potential determinants of vaccine protection. Neutralization activity against the homologous Env or challenge strain-specific Env in immune sera from the vaccinated ponies did not correlate with protection from disease. Cellular analysis with Env peptide pools did not reveal an association with vaccine protection from disease. However, when individual vaccine-specific Env peptides were utilized, eight cytotoxic-T-lymphocyte (CTL) peptides were found to associate closely with vaccine protection. One of these peptides also yielded the only lymphoproliferative response associated with protective immunity. The identified peptides spanned both variable and conserved regions of gp90. Amino acid divergence within the principal neutralization domain and the identified peptides profoundly affected immune recognition, as illustrated by the inability to detect cross-reactive neutralizing antibodies and the observation that certain peptide-specific CTL responses were altered. In addition to identifying potential Env determinants of EIAV vaccine efficacy and demonstrating the profound effects of defined Env variation on immune recognition, these data also illustrate the sensitivity offered by individual peptides compared to peptide pools in measuring cellular immune responses in lentiviral vaccine trials.

scholarly journals Natural Variation of Equine Infectious Anemia Virus Gag Protein Cytotoxic T Lymphocyte Epitopes

Virology ◽  
1999 ◽  
Vol 261 (2) ◽  
pp. 242-252 ◽  
Author(s):  
Wei Zhang ◽  
David B. Auyong ◽  
J.Lindsay Oaks ◽  
Travis C. McGuire
Keyword(s):  
T Lymphocyte ◽  
Natural Variation ◽  
Equine Infectious Anemia Virus ◽  
Cytotoxic T Lymphocyte ◽  
Gag Protein ◽  
Equine Infectious Anemia ◽  
Anemia Virus

scholarly journals Evaluation of equine infectious anemia virus by the indirect ELISA EIA-LAB as screening tools in Mexico

2021 ◽  
pp. 103372
Author(s):  
Maria Carla Rodríguez Domínguez ◽  
Roberto Montes-de-Oca-Jiménez ◽  
Juan Carlos Vázquez Chagoyan ◽  
Alberto Barbabosa Pliego ◽  
Jorge Antonio Varela Guerrero ◽  
...  
Keyword(s):  
Equine Infectious Anemia Virus ◽  
Indirect Elisa ◽  
Screening Tools ◽  
Equine Infectious Anemia ◽  
Anemia Virus

scholarly journals Mapping of Equine Lentivirus Receptor 1 Residues Critical for Equine Infectious Anemia Virus Envelope Binding

2007 ◽  
Vol 82 (3) ◽  
pp. 1204-1213 ◽  
Author(s):  
Baoshan Zhang ◽  
Chengqun Sun ◽  
Sha Jin ◽  
Michael Cascio ◽  
Ronald C. Montelaro
Keyword(s):  
Equine Infectious Anemia Virus ◽  
Tumor Necrosis Factor Receptor ◽  
Binding Domain ◽  
Virus Envelope ◽  
Immunodeficiency Virus ◽  
Equine Infectious Anemia ◽  
Anemia Virus ◽  
Functional Receptor ◽  
Herpesvirus Entry Mediator ◽  
Necrosis Factor

ABSTRACT The equine lentivirus receptor 1 (ELR1), a member of the tumor necrosis factor receptor (TNFR) protein family, has been identified as a functional receptor for equine infectious anemia virus (EIAV). Toward defining the functional interactions between the EIAV SU protein (gp90) and its ELR1 receptor, we mapped the gp90 binding domain of ELR1 by a combination of binding and functional assays using the EIAV SU gp90 protein and various chimeric receptor proteins derived from exchanges between the functional ELR1 and the nonbinding homolog, mouse herpesvirus entry mediator (murine HveA). Complementary exchanges of the respective cysteine-rich domains (CRD) between the ELR1 and murine HveA proteins revealed CRD1 as the predominant determinant of functional gp90 binding to ELR1 and also to a chimeric murine HveA protein expressed on the surface of transfected Cf2Th cells. Mutations of individual amino acids in the CRD1 segment of ELR1 and murine HveA indicated the Leu70 in CRD1 as essential for functional binding of EIAV gp90 and for virus infection of transduced Cf2Th cells. The specificity of the EIAV SU binding domain identified for the ELR1 receptor is fundamentally identical to that reported previously for functional binding of feline immunodeficiency virus SU to its coreceptor CD134, another TNFR protein. These results indicate unexpected common features of the specific mechanisms by which diverse lentiviruses can employ TNFR proteins as functional receptors.

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