Immunogenicity of HIV-1 IIIB and SHIV 89.6P Tat and Tat Toxoids in Rhesus Macaques: Induction of Humoral and Cellular Immune Responses

Richardson, Max W.; Mirchandani, Jyotika; Silvera, Peter; Régulier, Emmanuel G.; Capini, Christelle; Bojczuk, Paul M.; Hu, Jason; Gracely, Edward J.; Boyer, Jean D.; Khalili, Kamel; Zagury, Jean-François; Lewis, Mark G.; Rappaport, Jay
September 2002
DNA & Cell Biology;Sep2002, Vol. 21 Issue 9, p637
Academic Journal
This study compared immune responses in rhesus macaques immunized with unmodified HIV-1 IIIB Tat, SHIV89.6P Tat, and carboxymethylated IIIB and 89.6P Tat toxoids. Immunization with either IIIB or 89.6P preparation induced high titer and broadly crossreactive serum anti-Tat IgG that recognized HIV-1 subtype-E and SIVmac251 Tat. However, the response was delayed, and titers were lower in 89.6P vaccination groups. Serum anti-Tat IgG recognized peptides corresponding to the amino-terminus, basic domain, and carboxy-terminal region. Cellular proliferative responses to Tat toxoids corresponding to the immunogen were evident in vitro in both IIIB and 89.6P groups. Crossreactive proliferative responses were observed in IIIB groups in response to stimulation with 89.6P or SIVmac251 Tat toxoids, but were much less prevalent in 89.6P groups. The truncated 86 amino acid IIIB Tat appears to be more immunogenic than the 102 amino acid 89.6P Tat with respect to both humoral and cellular immune responses, and may be a better vaccine component. Despite induction of robust humoral and cellular immune responses (including both CD4+ and CD8+ T-cell responses) to Tat, all animals were infected upon intravenous challenge with 30 MID[sub 50] of SHIV89.6P and outcome of vaccine groups was not different from controls. Sequencing both Tat exons from serum viral RNA revealed no evidence of escape mutants. These results suggest that with intravenous SHIV89.6P challenge in rhesus macaques, precipitous CD4+ T-cell decline overwhelms potentially protective immune responses. Alternatively, Tat specific CD8+ T-cell responses may not appropriately recognize infected cells in vivo in this model. In view of evidence demonstrating Tat specific CTLs in the SIV model and in humans infected with HIV-1, results in this pathogenic SHIV model may not apparently predict the efficacy of this approach in human studies. The potency and cross-reactivity of these immune responses confirm Tat toxoid as an excellent candidate vaccine component.


Related Articles

  • Live attenuated rubella vectors expressing SIV and HIV vaccine antigens replicate and elicit durable immune responses in rhesus macaques. Virnik, Konstantin; Hockenbury, Max; Yisheng Ni; Beren, Joel; Pavlakis, George N.; Felber, Barbara K.; Berkower, Ira // Retrovirology;2013, Vol. 10 Issue 1, p1 

    Background: Live attenuated viruses are among our most potent and effective vaccines. For human immunodeficiency virus, however, a live attenuated strain could present substantial safety concerns. We have used the live attenuated rubella vaccine strain RA27/3 as a vector to express SIV and HIV...

  • Evaluation in Rhesus Macaques of Tat and Rev-Targeted Immunization as a Preventive Vaccine against Mucosal Challenge with SHIV-BX08. Verrier, Bernard; Le Grand, Roger; Ataman-Önal, Yasemin; Terrat, Celine; Guillon, Christophe; Durand, Pierre-Yves; Hurtrel, Bruno; Aubertin, Anne-Marie; Sutter, Gerd; Erfle, Volker; Girard, Marc // DNA & Cell Biology;Sep2002, Vol. 21 Issue 9, p653 

    Recent evidence suggests that a CD8-mediated cytotoxic T-cell response against the regulatory proteins of human immunodeficiency virus (HIV) or simian immunodeficiency virus (SIV) may control infection after pathogenic virus challenge. Here, we evaluated whether vaccination with Tat or Tat and...

  • Differences in time of virus appearance in the blood and virusspecific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; a pilot study. Stevceva, Liljana; Tryniszewska, Elzbieta; Hel, Zdenek; Nacsa, Janos; Kelsall, Brian; Parks, Robyn Washington; Franchini, Genoveffa // BMC Infectious Diseases;2001, Vol. 1 Issue 1, p1 

    Background: HIV-I can be transmitted by intravenous inoculation of contaminated blood or blood product or sexually through mucosal surfaces. Here we performed a pilot study in the SIVmac251 macaque model to address whether the route of viral entry influences the kinetics of the appearance and...

  • Activation of human CD4+ cells with CD3 and CD46 induces a T-regulatory cell 1 phenotype. Kemper, Claudia; Chan, Andrew C.; Green, Jonathan M.; Brett, Kelly A.; Murphy, Kenneth M.; Atkinson, John P. // Nature;1/23/2003, Vol. 421 Issue 6921, p388 

    The immune system must distinguish not only between self and non-self, but also between innocuous and pathological foreign antigens to prevent unnecessary or self-destructive immune responses. Unresponsiveness to harmless antigens is established through central and peripheral processes. Whereas...

  • Limited contribution of humoral immunity to the clearance of measles viremia in rhesus monkeys. Permar, Sallie R.; Klumpp, Sherry A.; Mansfield, Keith G.; Carville, Angela A.L.; Gorgone, Darci A.; Lifton, Michelle A.; Schmitz, Jörn E.; Reimann, Keith A.; Polack, Fernando P.; Griffin, Diane E.; Letvin, Norman L.; Schmitz, Jörn E // Journal of Infectious Diseases;9/1/2004, Vol. 190 Issue 5, p998 

    The development of an improved vaccine for controlling measles virus (MV) infections in the developing world will require an understanding of the immune mechanisms responsible for the clearance of this virus. To evaluate the role of humoral immunity in the containment of MV, rhesus monkeys were...

  • Viral Immunity: Therapeutic HIV vaccines. Buckland, Jenny // Nature Reviews Immunology;Feb2003, Vol. 3 Issue 2, p91 

    Discusses research being done on an immune response to simian immunodeficiency virus (SIV) elicited in vivo by a therapeutic dendritic cell vaccine. Reference to a study by W. Lu and colleagues, published in 'Nature Medicine' journal; Assessment of SIV-specific immunity; Experiment on...

  • Gene gun-based nucleic acid immunization alone or in combination with recombinant vaccinia vectors suppresses virus burden in rhesus macaques challenged with a heterologous SIV. Fuller, Deborah Heydenburg; Simpson, Laura; Cole, Kelly Stefano; Clements, Janice E.; Panicali, Dennis L.; Montelaro, Ronald C.; Murphey-corb, Michael; Haynesh, Joel R. // Immunology & Cell Biology;Aug1997, Vol. 75 Issue 4, p389 

    Gene gun-based DNA immunization alone or in combination with recombinant vaccinia vectors was evaluated for the ability to elicit protective immune responses in rhesus macaques challenged with a pathogenic, heterologous simian immunodeficiency virus (SIV). Six monkeys primed with seven...

  • © Effect of chloroquine on cellular immune responses of normal and P. knowlesi-infected rhesus monkeys. Prasad, R. N.; Mahajan, R. C.; Ganguly, N. K. // Immunology & Cell Biology;Jun1987, Vol. 65 Issue 3, p211 

    The immunopharmacokinetics of chloroquine were studied in Plasmodium Knowlest-infected and uninfected rhesus monkeys. In control monkeys, chloroquine depressed the percentage of lymphocyte subpopulation and their proliferative response after the third dose of drug administration. The effect was...

  • Inhibition of costimulation allows for repeated systemic administration of adenoviral vector in rhesus monkeys. Haegel-Kronenberger, H.; Haanstra, K.; Ziller-Remy, C.; Buijsse, A.P. Ortiz; Vermeiren, J.; Stoeckel, F.; van Gool, S.W.; Ceuppens, J.L.; Mehtali, M.; de Boer, M.; Jonker, M.; Boon, Louis // Gene Therapy;Feb2004, Vol. 11 Issue 3, p241 

    Immunogenicity of recombinant adenoviral (Ad) vectors severely hampers the clinical development of gene therapy protocols using repeated vector administrations. Inhibition of costimulation by APCs was explored as a strategy to circumvent the immune response against Ad particles. This strategy...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics