Increased cellular immune responses and CD4+ T-cell proliferation correlate with reduced plasma viral load in SIV challenged recombinant simian varicella virus - simian immunodeficiency virus (rSVV-SIV) vaccinated rhesus macaques

Virology Journal

Vicki L Traina-Dorge¹  Preston A Marx⁵  Eileen deHaro⁵  Elizabeth S Didier⁵  Kimberly Phelps²  Wayne L Gray³  Bapi Pahar⁴ 

[1] Division of Microbiology, Tulane National Primate Research Center, 18703 Three Rivers Road, Covington, LA 70433, USA;Departments of Chemistry and Physics, College of Sciences, Louisiana State University Shreveport, Shreveport, LA, USA;University of Arkansas for Medical Sciences, Little Rock, AR, USA;Division of Comparative Pathology, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA, USA;Division of Microbiology, Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA USA

关键词: Vaccine;    Proliferation;    Memory;    Cytokine;    T-cells;    Simian immunodeficiency virus (SIV);    Simian varicella virus (SVV);   

Others  :  1154160
DOI  :  10.1186/1743-422X-9-160

 received in 2012-02-14, accepted in 2012-07-11,  发布年份 2012

【 摘 要 】

Background

An effective AIDS vaccine remains one of the highest priorities in HIV-research. Our recent study showed that vaccination of rhesus macaques with recombinant simian varicella virus (rSVV) vector – simian immunodeficiency virus (SIV) envelope and gag genes, induced neutralizing antibodies and cellular immune responses to SIV and also significantly reduced plasma viral loads following intravenous pathogenic challenge with SIV_MAC251/CX1.

Findings

The purpose of this study was to define cellular immunological correlates of protection in rSVV-SIV vaccinated and SIV challenged animals. Immunofluorescent staining and multifunctional assessment of SIV-specific T-cell responses were evaluated in both Experimental and Control vaccinated animal groups. Significant increases in the proliferating CD4+ T-cell population and polyfunctional T-cell responses were observed in all Experimental-vaccinated animals compared with the Control-vaccinated animals.

Conclusions

Increased CD4+ T-cell proliferation was significantly and inversely correlated with plasma viral load. Increased SIV-specific polyfunctional cytokine responses and increased proliferation of CD4+ T-cell may be crucial to control plasma viral loads in vaccinated and SIV_MAC251/CX1 challenged macaques.

【 授权许可】

   
2012 Pahar et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Pahar B, Lackner AA, Piatak M Jr, Lifson JD, Wang X, Das A, Ling B, Montefiori DC, Veazey RS: Control of viremia and maintenance of intestinal CD4(+) memory T-cells in SHIV(162P3) infected macaques after pathogenic SIV(MAC251) challenge. Virology 2009, 387:273-284.
• [2]Koff WC, Johnson PR, Watkins DI, Burton DR, Lifson JD, Hasenkrug KJ, McDermott AB, Schultz A, Zamb TJ, Boyle R, Desrosiers RC: HIV vaccine design: insights from live attenuated SIV vaccines. Nat Immunol 2006, 7:19-23.
• [3]Marthas ML, Miller CJ, Sutjipto S, Higgins J, Torten J, Lohman BL, Unger RE, Ramos RA, Kiyono H, McGhee JR, et al.: Efficacy of live-attenuated and whole-inactivated simian immunodeficiency virus vaccines against vaginal challenge with virulent SIV. J Med Primatol 1992, 21:99-107.
• [4]Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, et al.: Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009, 361:2209-2220.
• [5]Barouch DH, Liu J, Li H, Maxfield LF, Abbink P, Lynch DM, Iampietro MJ, Sanmiguel A, Seaman MS, Ferrari G, et al.: Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature 2012, 482:89-93.
• [6]Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, Whizin N, Oswald K, Shoemaker R, Swanson T, et al.: Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 2011, 473:523-527.
• [7]Arvin AM, Mallory S, Moffat JF: Development of recombinant varicella-zoster virus vaccines. Contrib Microbiol 1999, 3:193-200.
• [8]Gray WL: Simian varicella: a model for human varicella-zoster virus infections. Rev Med Virol 2004, 14:363-381.
• [9]Gray WL: Simian varicella in old world monkeys. Comp Med 2008, 58:22-30.
• [10]Traina-Dorge V, Pahar B, Marx P, Kissinger P, Montefiori D, Ou Y, Gray WL: Recombinant varicella vaccines induce neutralizing antibodies and cellular immune responses to SIV and reduce viral loads in immunized rhesus macaques. Vaccine 2010, 28:6483-6490.
• [11]Ou Y, Traina-Dorge V, Davis KA, Gray WL: Recombinant simian varicella viruses induce immune responses to simian immunodeficiency virus (SIV) antigens in immunized vervet monkeys. Virology 2007, 364:291-300.
• [12]Pahar B, Cantu MA, Zhao W, Kuroda MJ, Veazey RS, Montefiori DC, Clements JD, Aye PP, Lackner AA, Lovgren-Bengtsson K, Sestak K: Single epitope mucosal vaccine delivered via immuno-stimulating complexes induces low level of immunity against simian-HIV. Vaccine 2006, 24:6839-6849.
• [13]Hazenberg MD, Stuart JW, Otto SA, Borleffs JC, Boucher CA, de Boer RJ, Miedema F, Hamann D: T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART). Blood 2000, 95:249-255.
• [14]Kaur A, Hale CL, Ramanujan S, Jain RK, Johnson RP: Differential dynamics of CD4(+) and CD8(+) T-lymphocyte proliferation and activation in acute simian immunodeficiency virus infection. J Virol 2000, 74:8413-8424.
• [15]Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B, Jacobson LP, Shih R, Lewis J, Wiley DJ, Phair JP, et al.: Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis 1999, 179:859-870.
• [16]Pahar B, Wang X, Dufour J, Lackner AA, Veazey RS: Virus-specific T-cell responses in macaques acutely infected with SHIV(sf162p3). Virology 2007, 363:36-47.
• [17]Chevalier MF, Julg B, Pyo A, Flanders M, Ranasinghe S, Soghoian DZ, Kwon DS, Rychert J, Lian J, Muller MI, et al.: HIV-1-specific interleukin-21+ CD4+ T-cell responses contribute to durable viral control through the modulation of HIV-specific CD8+ T-cell function. J Virol 2011, 85:733-741.
• [18]Norris PJ, Moffett HF, Yang OO, Kaufmann DE, Clark MJ, Addo MM, Rosenberg ES: Beyond help: direct effector functions of human immunodeficiency virus type 1-specific CD4(+) T-cells. J Virol 2004, 78:8844-8851.
• [19]Soghoian DZ, Streeck H: Cytolytic CD4(+) T-cells in viral immunity. Expert Rev Vaccines 2010, 9:1453-1463.
• [20]Harari A, Petitpierre S, Vallelian F, Pantaleo G: Skewed representation of functionally distinct populations of virus-specific CD4 T-cells in HIV-1-infected subjects with progressive disease: changes after antiretroviral therapy. Blood 2004, 103:966-972.
• [21]Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD: Vigorous HIV-1-specific CD4+ T-cell responses associated with control of viremia. Science 1997, 278:1447-1450.
• [22]Douek DC, Brenchley JM, Betts MR, Ambrozak DR, Hill BJ, Okamoto Y, Casazza JP, Kuruppu J, Kunstman K, Wolinsky S, et al.: HIV preferentially infects HIV-specific CD4+ T-cells. Nature 2002, 417:95-98.