Improved protection against simian immunodeficiency virus mucosal challenge in macaques primed with a DNA vaccine and boosted with the recombinant modified vaccinia virus Ankara and recombinant Semliki Forest virus
ABSTRACT Using the experimental infection of cynomolgus macaques with simian immunodeficiency virus (SIV) as a model of human immunodeficiency virus infection in humans, we studied the immunogenicity and protective efficacy of a vaccine strategy combining DNA, the modified recombinant vaccinia virus strain Ankara (MVA) and Semliki Forest virus (SFV) expressing gag, pol, env, tat, rev and nef from SIV. Although this immunization strategy induced moderate immune responses, the control of pathogenic SIVmac251 infection following mucosal challenge was clearly improved by vaccination. The viral load in vaccinated animals was reduced by 2 logs during the acute phase of infection and, in five of the six macaques, viral load fell below the detection limit at set point. No correlates of immune protection were identified, but SIV-specific T-cell responses were detected earlier in vaccinated animals than in controls. These results highlight the power of live attenuated virus vectors for vaccination strategies.
SourceAvailable from: Oscar Bruna-Romero[Show abstract] [Hide abstract]
ABSTRACT: Owing to the importance of major histocompatibility complex class Ia-restricted CD8(+) T cells for host survival following viral, bacterial, fungal, or parasitic infection, it has become largely accepted that these cells should be considered in the design of a new generation of vaccines. For the past 20 years, solid evidence has been provided that the heterologous prime-boost regimen achieves the best results in terms of induction of long-lived protective CD8(+) T cells against a variety of experimental infections. Although this regimen has often been used experimentally, as is the case for many vaccines, the mechanism behind the efficacy of this vaccination regimen is still largely unknown. The main purpose of this review is to examine the characteristics of the protective CD8(+) T cells generated by this vaccination regimen. Part of its efficacy certainly relies on the generation and maintenance of large numbers of specific lymphocytes. Other specific characteristics may also be important, and studies on this direction have only recently been initiated. So far, the characterization of these protective, long-lived T cell populations suggests that there is a high frequency of polyfunctional T cells; these cells cover a large breadth and display a T effector memory (TEM) phenotype. These TEM cells are capable of proliferating after an infectious challenge and are highly refractory to apoptosis due to a control of the expression of pro-apoptotic receptors such as CD95. Also, they do not undergo significant long-term immunological erosion. Understanding the mechanisms that control the generation and maintenance of the protective activity of these long-lived TEM cells will certainly provide important insights into the physiology of CD8(+) T cells and pave the way for the design of new or improved vaccines.Frontiers in Immunology 12/2012; 3:358. DOI:10.3389/fimmu.2012.00358
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ABSTRACT: Cervical cancer is the second most common cause of cancer death in women worldwide and the development of new diagnosis, prognostic, and treatment strategies merits special attention. Although surgery and chemoradiotherapy can cure 80%-95% of women with early stage cancer, the recurrent and metastatic disease remains a major cause of cancer death. Many efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent decades, research on treatment strategies has proposed several options, including the role of HPV E6 and E7 oncogenes, which are retained and expressed in most cervical cancers and whose respective oncoproteins are critical to the induction and maintenance of the malignant phenotype. Other efforts have been focused on antitumor immunotherapy strategies. It is known that during the development of cervical cancer, a cascade of abnormal events is induced, including disruption of cellular cycle control, perturbation of antitumor immune response, alteration of gene expression, and deregulation of microRNA expression. Thus, in this review article we discuss potential targets for the treatment of cervical cancer associated with HPV infection, with special attention to immunotherapy approaches, clinical trials, siRNA molecules, and their implications as gene therapy strategies against cervical cancer development.OncoTargets and Therapy 11/2012; 5:315-28. DOI:10.2147/OTT.S25123 · 1.34 Impact Factor
International Reviews Of Immunology 01/2009; · 5.28 Impact Factor