A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine.
Abstract: Data from successful attenuated lentiviral vaccine studies indicate that fully mature Env-specific antibodies characterized by high titer, high avidity, and the predominant recognition of conformational epitopes are associated with protective efficacy. Although vaccination with a DNA prime/recombinant vaccinia-vectored vaccine boost strategy has been found to be effective in some trials with non-human primate/simian/human immunodeficiency virus (SHIV) models, it remains unclear whether this vaccination strategy could elicit mature equine infectious anemia virus (EIAV) Env-specific antibodies, thus protecting vaccinated horses against EIAV infection. Therefore, in this pilot study we vaccinated horses using a strategy based on DNA prime/recombinant Tiantan vaccinia (rTTV)-vectored vaccines encoding EIAV env and gag genes, and observed the development of Env-specific antibodies, neutralizing antibodies, and p26-specific antibodies. Vaccination with DNA induced low titer, low avidity, and the predominant recognition of linear epitopes by Env-specific antibodies, which was enhanced by boosting vaccinations with rTTV vaccines. However, the maturation levels of Env-specific antibodies induced by the DNA/rTTV vaccines were significantly lower than those induced by the attenuated vaccine EIAV(FDDV). Additionally, DNA/rTTV vaccines did not elicit broadly neutralizing antibodies. After challenge with a virulent EIAV strain, all of the vaccinees and control horses died from EIAV disease. These data indicate that the regimen of DNA prime/rTTV vaccine boost did not induce mature Env-specific antibodies, which might have contributed to immune protection failure.
Publication Date: 2012-11-21 PubMed ID: 23171359PubMed Central: PMC3518545DOI: 10.1089/vim.2012.0014Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research study discusses comparing the development of antibodies induced by DNA/recombinant vaccinia-vectored vaccines to an attenuated Chinese EIAV vaccine for equine infectious anemia virus (EIAV). The study concluded that DNA/recombinant vaccines did not induce mature antibodies and did not protect horses from EIAV infection.
Objective and Methods
- The primary aim of this research study was to examine and compare the effectiveness of DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine on the development of antibodies, designed to combat Equine Infectious Anemia Virus (EIAV). The hypothesis being tested was whether the DNA prime/recombinant Tiantan vaccinia-vectored vaccines encoding EIAV env and gag genes could stimulate the development of mature EIAV Env-specific antibodies, thereby offering protection against EIAV infection.
- To do so, horses were vaccinated using a strategy consisting of a DNA prime vaccination followed by a boost of recombinant Tiantan vaccinia-vectored vaccines. Subsequently, the development of specific antibodies (Env-specific antibodies, neutralizing antibodies, and p26-specific antibodies) was monitored.
Findings
- The initial vaccination with DNA induced a low level and low avidity response from Env-specific antibodies, though this response was slightly enhanced by sequential administrations of recombinant Tiantan vaccinia vaccines.
- Importantly, the degree of maturation achieved by Env-specific antibodies due to the DNA/recombinant vaccines was significantly lower than from the attenuated EIAV vaccine, raising questions about the protective capacity of the DNA/recombinant vaccines.
- The study data further exhibited that DNA/recombinant vaccinia-vectored vaccines not only failed to elicit strong, mature Env-specific antibodies but they also did not stimulate the production of broadly neutralizing antibodies.
- Following exposure to a virulent EIAV strain, all horses, regardless of their vaccination status, succumbed to the EIAV disease. This starkly demonstrates that the DNA prime/recombinant Tiantan vaccinia-vectored vaccine regimen did not yield mature, Env-specific antibodies, resulting in the failure of immune protection.
Conclusions
- This pilot study provides valuable insights into the limited effectiveness of DNA/recombinant vaccinia-vectored vaccines against EIAV infection. It serves as a key, cautionary indication that such vaccines, despite their efficacy in other contexts, may not be similarly suitable or effective for combating EIAV.
- The study concludes by suggesting that a deeper understanding of the immunological interactions, and an optimized vaccination strategy, may be required to induce a stronger, more protective immune response leading to enhanced protective efficacy against EIAV infection.
Cite This Article
APA
Meng Q, Lin Y, Ma J, Ma Y, Zhao L, Li S, Yang K, Zhou J, Shen R, Zhang X, Shao Y.
(2012).
A pilot study comparing the development of EIAV Env-specific antibodies induced by DNA/recombinant vaccinia-vectored vaccines and an attenuated Chinese EIAV vaccine.
Viral Immunol, 25(6), 477-484.
https://doi.org/10.1089/vim.2012.0014 Publication
Researcher Affiliations
- State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
MeSH Terms
- Animals
- Antibodies, Neutralizing / blood
- Antibodies, Viral / blood
- Equine Infectious Anemia / prevention & control
- Horses
- Infectious Anemia Virus, Equine / immunology
- Pilot Projects
- Survival Analysis
- Vaccination / methods
- Vaccines, Attenuated / administration & dosage
- Vaccines, Attenuated / immunology
- Vaccines, DNA / administration & dosage
- Vaccines, DNA / immunology
- Viral Envelope Proteins / immunology
- Viral Vaccines / administration & dosage
- Viral Vaccines / immunology
References
This article includes 29 references
- Bråve A, Ljungberg K, Wahren B, Liu MA. Vaccine delivery methods using viral vectors.. Mol Pharm 2007 Jan-Feb;4(1):18-32.
- Cole KS, Rowles JL, Jagerski BA, Murphey-Corb M, Unangst T, Clements JE, Robinson J, Wyand MS, Desrosiers RC, Montelaro RC. Evolution of envelope-specific antibody responses in monkeys experimentally infected or immunized with simian immunodeficiency virus and its association with the development of protective immunity.. J Virol 1997 Jul;71(7):5069-79.
- Cook RF, Cook SJ, Bolin PS, Howe LJ, Zhou W, Montelaro RC, Issel CJ. Genetic immunization with codon-optimized equine infectious anemia virus (EIAV) surface unit (SU) envelope protein gene sequences stimulates immune responses in ponies.. Vet Microbiol 2005 Jun 15;108(1-2):23-37.
- Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC. Discerning an effective balance between equine infectious anemia virus attenuation and vaccine efficacy.. J Virol 2005 Mar;79(5):2666-77.
- Craigo JK, Zhang B, Barnes S, Tagmyer TL, Cook SJ, Issel CJ, Montelaro RC. Envelope variation as a primary determinant of lentiviral vaccine efficacy.. Proc Natl Acad Sci U S A 2007 Sep 18;104(38):15105-10.
- Donnelly JJ, Wahren B, Liu MA. DNA vaccines: progress and challenges.. J Immunol 2005 Jul 15;175(2):633-9.
- Fraser DG, Leib SR, Zhang BS, Mealey RH, Brown WC, McGuire TC. Lymphocyte proliferation responses induced to broadly reactive Th peptides did not protect against equine infectious anemia virus challenge.. Clin Diagn Lab Immunol 2005 Aug;12(8):983-93.
- Hammond SA, Cook SJ, Falo LD Jr, Issel CJ, Montelaro RC. A particulate viral protein vaccine reduces viral load and delays progression to disease in immunized ponies challenged with equine infectious anemia virus.. Virology 1999 Feb 1;254(1):37-49.
- Hammond SA, Cook SJ, Lichtenstein DL, Issel CJ, Montelaro RC. Maturation of the cellular and humoral immune responses to persistent infection in horses by equine infectious anemia virus is a complex and lengthy process.. J Virol 1997 May;71(5):3840-52.
- Huang X, Lu B, Yu W, Fang Q, Liu L, Zhuang K, Shen T, Wang H, Tian P, Zhang L, Chen Z. A novel replication-competent vaccinia vector MVTT is superior to MVA for inducing high levels of neutralizing antibody via mucosal vaccination.. PLoS One 2009;4(1):e4180.
- Issel CJ, Coggins L. Equine infectious anemia: current knowledge.. J Am Vet Med Assoc 1979 Apr 1;174(7):727-33.
- Issel CJ, Horohov DW, Lea DF, Adams WV Jr, Hagius SD, McManus JM, Allison AC, Montelaro RC. Efficacy of inactivated whole-virus and subunit vaccines in preventing infection and disease caused by equine infectious anemia virus.. J Virol 1992 Jun;66(6):3398-408.
- Koup RA, Roederer M, Lamoreaux L, Fischer J, Novik L, Nason MC, Larkin BD, Enama ME, Ledgerwood JE, Bailer RT, Mascola JR, Nabel GJ, Graham BS. Priming immunization with DNA augments immunogenicity of recombinant adenoviral vectors for both HIV-1 specific antibody and T-cell responses.. PLoS One 2010 Feb 2;5(2):e9015.
- Li F, Craigo JK, Howe L, Steckbeck JD, Cook S, Issel C, Montelaro RC. 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 Jul;77(13):7244-53.
- Liang H, He X, Shen RX, Shen T, Tong X, Ma Y, Xiang WH, Zhang XY, Shao YM. Combined amino acid mutations occurring in the envelope closely correlate with pathogenicity of EIAV.. Arch Virol 2006 Jul;151(7):1387-403.
- Ma J, Shi N, Jiang CG, Lin YZ, Wang XF, Wang S, Lv XL, Zhao LP, Shao YM, Kong XG, Zhou JH, Shen RX. A proviral derivative from a reference attenuated EIAV vaccine strain failed to elicit protective immunity.. Virology 2011 Feb 5;410(1):96-106.
- Mealey RH, Leib SR, Littke MH, Wagner B, Horohov DW, McGuire TC. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen.. Vaccine 2009 Apr 21;27(18):2453-68.
- Meng Q, Li S, Liu L, Xu J, Liu Y, Zhang Y, Zhang X, Shao Y. Truncation of cytoplasmic tail of EIAV Env increases the pathogenic necrosis.. Virus Res 2008 May;133(2):201-10.
- Meng Q, Lin Y, Ma J, Ma Y, Zhao L, Li S, Liang H, Zhou J, Shen R, Zhang X, Shao Y. A pilot study on an attenuated Chinese EIAV vaccine inducing broadly neutralizing antibodies.. Arch Virol 2011 Aug;156(8):1455-62.
- Raabe ML, Issel CJ, Cook SJ, Cook RF, Woodson B, Montelaro RC. Immunization with a recombinant envelope protein (rgp90) of EIAV produces a spectrum of vaccine efficacy ranging from lack of clinical disease to severe enhancement.. Virology 1998 May 25;245(1):151-62.
- Richmond JF, Lu S, Santoro JC, Weng J, Hu SL, Montefiori DC, Robinson HL. Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting.. J Virol 1998 Nov;72(11):9092-100.
- Richmond JF, Mustafa F, Lu S, Santoro JC, Weng J, O'Connell M, Fenyö EM, Hurwitz JL, Montefiori DC, Robinson HL. Screening of HIV-1 Env glycoproteins for the ability to raise neutralizing antibody using DNA immunization and recombinant vaccinia virus boosting.. Virology 1997 Apr 14;230(2):265-74.
- Sellon DC, Fuller FJ, McGuire TC. The immunopathogenesis of equine infectious anemia virus.. Virus Res 1994 May;32(2):111-38.
- Shen R, Wang Z, Dong J. Fetal donkey dermal cells adapted attenuated vaccine of equine infectious anemia virus, its culture method. 2001.
- Shen R, Xu Z, He Y, Zhang S. Study on vaccination of equine infectious anemia. Chin Agricult Sci 1979;12:1–15.
- Shen T, Liang H, Tong X, Fan X, He X, Ma Y, Xiang W, Shen R, Zhang X, Shao Y. Amino acid mutations of the infectious clone from Chinese EIAV attenuated vaccine resulted in reversion of virulence.. Vaccine 2006 Feb 6;24(6):738-49.
- Singh N, Pandey A, Jayashankar L, Mittal SK. Bovine adenoviral vector-based H5N1 influenza vaccine overcomes exceptionally high levels of pre-existing immunity against human adenovirus.. Mol Ther 2008 May;16(5):965-71.
- Tagmyer TL, Craigo JK, Cook SJ, Even DL, Issel CJ, Montelaro RC. Envelope determinants of equine infectious anemia virus vaccine protection and the effects of sequence variation on immune recognition.. J Virol 2008 Apr;82(8):4052-63.
- Xu J, Ren L, Huang X, Qiu C, Liu Y, Liu Y, Shao Y. Sequential priming and boosting with heterologous HIV immunogens predominantly stimulated T cell immunity against conserved epitopes.. AIDS 2006 Nov 28;20(18):2293-303.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists