Silmi Mariya

Therapeutic Vaccine Against Primate Papillomavirus Infections of the Cervix

Currently available prophylactic vaccines have no therapeutic efficacy for preexisting human papillomavirus (HPVs) infections, do not target all oncogenic HPVs and are insufficient to eliminate the burden of HPV induced cancer. We aim to develop an alternative HPV vaccine which is broadly effective and capable of clearing preexisting infection. In an initial attempt to develop a broadly reactive therapeutic vaccine, we designed a putative papillomavirus (PV) ancestor antigen (circulating sequence derived antigenic sequences E1E2—CDSE1E2) based on the conserved E1 and E2 protein sequences from existing oncogenic HPV strains. This antigen was found to be as related to circulating oncogenic Macaca fascicularis papillomaviruses (MfPVs) as to oncogenic HPVs. The CDSE1E2 antigen was fused to a T-cell adjuvant and encoded in chimpanzee 3 and 63 adenoviral vectors. We first showed that the combination of these 2 vaccines induced long-lasting potent CDSE1E2 specific T cell responses in outbred mice. This prime-boost regimen was then tested in female macaques naturally infected with MfPVs. All immunized animals (16/16) responded to the vaccine antigen but with reduced cross-reactivity against existing PVs. Preexisting MfPV infections did not prime vaccine inducible immune responses. Importantly, immunized oncogenic MfPV type 3 (MfPV3) infected animals that responded toward MfPV3 were able to diminish cervical MfPV3 DNA content. Although insufficient breadth was achieved, our results suggest that a relevant level of E1E2 specific T cell immunity is achievable and might be sufficient for the elimination of PV infection. Importantly, naturally infected macaques, offer a relevant model for testing vaccines aimed at eliminating mucosal PV infections.

Replication deficient human adenovirus vector serotype 19a/64: Immunogenicity in mice and female cynomolgus macaques

The human adenovirus type 19a/64 (hAd19a) is a rare serotype in the human population that transduces human dendritic cells (DCs) and human muscle cells more efficiently than the well-characterized human adenovirus type 5 (hAd5). To further characterize the potential of this vector as a vaccine we designed replication deficient hAd19a, hAd5 and MVA vectors expressing a papillomavirus (PV) antigen fused to the human MHC class II associated invariant chain T cell adjuvant (hIi) and investigated their immunogenicity in vivo in mice and cynomolgus macaques. We initially showed that the hIi encoded in the hAd5 enhanced PV specific CD8+ T cell responses in mice. The T cell responses induced after hAd19a vaccination was similar to those induced by hAd5 vaccination. The hAd19a induced responses were not reduced in presence of preexisting Ad5 immunity in mice. In macaques both vaccines were equally potent at inducing CD8+ T cells after MVA boost, while the level of CD4+ T cell responses were found to be broader in hAd19a primed animals. These data demonstrate the potential of hAd19a as an alternative vector to hAd5 to elicit potent T cell responses to PV.

Isolation, Culture and Characterization of Cancer Stem Cells from Primary Osteosarcoma

RESEARCH ARTICLE Isolation, Culture and Characterization of Cancer Stem Cells from Primary Osteosarcoma Achmad Fauzi Kamal , Deded Yudha Pranatha, Waluyo Sugito, Faisal Rahman, Eka Susanto, Silmi Mariya and Wei Ming Chen Department of Orthopaedic & Traumatology, Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia Stem Cell Integrated Medical Technology Unit, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia Department of Anatomic Pathology, Cipto Mangunkusumo General Hospital, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia Primate Research Center, Bogor Agricultural Institute, Bogor, Indonesia Department of Orthopaedic Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

Gender, age and differences in stem cell expression and efficacy

Submit Manuscript | http://medcraveonline.com examples of age and gender differences in the risk of chronic conditions such as heart disease, osteoporosis and urogenital dysfunction. There are also differences in the ability of different genders and ages to respond to treatments. It stands to reason there may be age and gender differences in their ability to regenerate tissues in response to cell therapy. This review will address the evidence for and against these potential differences.