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 Protective Efficacy of an Inactive Vaccine Based on the LY02 Isolate against AcuteHaemophilus parasuisInfection in Piglets

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-Hua Li ◽  
Guo-Zhen Zhao ◽  
Long-Xin Qiu ◽  
Ai-Ling Dai ◽  
Wang-Wei Wu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Haemophilus Parasuis ◽  
Fujian Province ◽  
Cellular Immune Responses ◽  
Glässer’S Disease ◽  
Potential Vaccine ◽  
Cellular Immune ◽  
Glasser's Disease

Haemophilus parasuiscan cause Glässer’s disease characterized by fibrinous polyserositis, polyarthritis, and meningitis. The current prevention of Glässer’s disease is mainly based on the inactive vaccines; however, the protective efficacy usually fails in heterogeneous or homologous challenges. Here, the predominant lineage ofH. parasuis(LY02 strain) in Fujian province, China, characterized as serovar 5, was used to evaluate the protective immunity against acuteH. parasuisinfection in piglets after inactivation. Following challenging withH. parasuis,only mild lesions in the pigs immunized with the killed vaccine were observed, whereas the typical symptoms of Glässer’s disease presented in the nonimmunized piglets. A strong IgG immune response was induced by the inactive vaccine. CD4+and CD8+T lymphocyte levels were increased, indicating the potent cellular immune responses were elicited. The significantly high levels of IL-2, IL-4, TGF-β, and IFN-γin sera from pigs immunized with this killed vaccine suggested that the mixed Th1 and Th2 immune responses were induced, associated with the high protection againstH. parasuisinfection compared to the nonimmunized animals. This study indicated that the inactivated LY02 strain ofH. parasuiscould serve as a potential vaccine candidate to prevent the prevalence ofH. parasuisin Fujian province, China.

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.

scholarly journals Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

2020 ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals Development of a multi-antigenic SARS-CoV-2 vaccine candidate using a synthetic poxvirus platform

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu H. Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We demonstrate the construction of a vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we use this vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. We show that mice immunized with these sMVA vectors develop robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine

2020 ◽  
Author(s):  
Flavia Chiuppesi ◽  
Marcela d’Alincourt Salazar ◽  
Heidi Contreras ◽  
Vu H Nguyen ◽  
Joy Martinez ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Vaccine Candidate ◽  
Vaccine Platform ◽  
Synthetic Dna ◽  
Cellular Immune Responses ◽  
Global Pandemic ◽  
Immunodominant Antigens ◽  
Cellular Immune

AbstractModified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

scholarly journals The determination of in vivo envelope-specific cell-mediated immune responses in equine infectious anemia virus-infected ponies

2012 ◽  
Vol 148 (3-4) ◽  
pp. 302-310 ◽  
Author(s):  
Chong Liu ◽  
Frank R. Cook ◽  
Sheila J. Cook ◽  
Jodi K. Craigo ◽  
Deborah L. Even ◽  
...  
Keyword(s):  
Immune Responses ◽  
Equine Infectious Anemia Virus ◽  
Specific Cell ◽  
Equine Infectious Anemia ◽  
Anemia Virus

scholarly journals Vaccine Protection by Live, Attenuated Simian Immunodeficiency Virus in the Absence of High-Titer Antibody Responses and High-Frequency Cellular Immune Responses Measurable in the Periphery

2008 ◽  
Vol 82 (8) ◽  
pp. 4135-4148 ◽  
Author(s):  
Keith Mansfield ◽  
Sabine M. Lang ◽  
Marie-Claire Gauduin ◽  
Hannah B. Sanford ◽  
Jeffrey D. Lifson ◽  
...  
Keyword(s):  
Immune Responses ◽  
High Frequency ◽  
High Titer ◽  
Antibody Responses ◽  
Wild Type ◽  
Vaccine Protection ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Cellular Immune

ABSTRACT An attenuated derivative of simian immunodeficiency virus strain 239 deleted of V1-V2 sequences in the envelope gene (SIV239ΔV1-V2) was used for vaccine/challenge experiments in rhesus monkeys. Peak levels of viral RNA in plasma of 104 to 106.5 copies/ml in the weeks immediately following inoculation of SIV239ΔV1-V2 were 10- to 1,000-fold lower than those observed with parental SIV239 (∼107.3 copies/ml). Viral loads consistently remained below 200 copies/ml after 8 weeks of infection by the attenuated SIV239ΔV1-V2 strain. Viral localization experiments revealed large numbers of infected cells within organized lymphoid nodules of the colonic gut-associated lymphoid tissue at 14 days; double-labeling experiments indicated that 93.5% of the virally infected cells at this site were positive for the macrophage marker CD68. Cellular and humoral immune responses measured principally by gamma interferon enzyme-linked immunospot and neutralization assays were variable in the five vaccinated monkeys. One monkey had responses in these assays comparable to or only slightly less than those observed in monkeys infected with parental, wild-type SIV239. Four of the vaccinated monkeys, however, had low, marginal, or undetectable responses in these same assays. These five vaccinated monkeys and three naïve control monkeys were subsequently challenged intravenously with wild-type SIV239. Three of the five vaccinated monkeys, including the one with strong anti-SIV immune responses, were strongly protected against the challenge on the basis of viral load measurements. Surprisingly, two of the vaccinated monkeys were strongly protected against SIV239 challenge despite the presence of cellular anti-SIV responses of low-frequency and low-titer anti-SIV antibody responses. These results indicate that high-titer anti-SIV antibody responses and high-frequency anti-SIV cellular immune responses measurable by standard assays from the peripheral blood are not needed to achieve strong vaccine protection, even against a difficult, neutralization-resistant strain such as SIV239.

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