Prophylactic human papillomavirus (HPV) vaccines are commercially available for prevention of infection with cancerogenic HPV genotypes but are not able to combat pre-existing HPV-associated disease. In this study, we designed a nanomaterial-based therapeutic HPV vaccine, comprising manganese (Mn)-doped silica nanoparticles (Mn-SNPs) and the viral neoantigen peptide GF001 derived from the HPV16 E7 oncoprotein. We show in mice that Mn-SNPs act as self-adjuvants by activating the inflammatory signaling pathway via generation of reactive oxygen species, resulting in immune cell recruitment to the immunization site and dendritic cell maturation.
View Article and Find Full Text PDFHigh-risk human papillomavirus infection can induce cervical and other intraepithelial neoplasia and invasive cancers. A transgenic mouse expressing keratin 14 promotor-driven HPV16 E7 oncoprotein exhibits epithelial hyperplasia and mimics many features of human papillomavirus-related intraepithelial precancers. We have previously demonstrated that HPV16 E7-mediated epithelial hyperplasia suppresses T helper type 1 responses to intradermally delivered antigen and directs differentiation of CD4 T cells towards a Foxp3 regulatory phenotype (Treg).
View Article and Find Full Text PDFHuman papillomaviruses infect keratinocytes and can lead to hyperproliferative dysplasia and malignant transformation if not cleared by the immune system. Human papillomavirus has evolved an array of mechanisms to evade and manipulate the immune system to improve replication efficiency and promote persistent infection. We here demonstrate that hyperproliferative skin expressing the high-risk human papillomavirus 16 E7 oncogene as a transgene drives immunomodulation of dendritic cells (DCs), resulting in reduced capacity to take up antigen and prime effector CD4 T cell responses.
View Article and Find Full Text PDFEthiop J Health Sci
November 2017
Background: Sexually transmitted infection (STI) is a major global cause of acute illness, infertility, long-term disability and death, with serious medical and psychological consequences to millions of men, women and infants. Moreover, in Ethiopia, epidemiological studies on STI among STI clinic clients are limited. Therefore, the aim of this study was to determine the prevalence and associated risk factors of sexually transmitted infection (STI).
View Article and Find Full Text PDFHigh-risk human papillomaviruses (HR-HPV) infect basal keratinocytes, where in some individuals they evade host immune responses and persist. Persistent HR-HPV infection of the cervix causes precancerous neoplasia that can eventuate in cervical cancer. Dendritic cells (DCs) are efficient in priming/cross-priming antigen-specific T cells and generating antiviral and antitumor cytotoxic CD8+ T cells.
View Article and Find Full Text PDFBackground: Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading causes of death from infectious diseases worldwide. Sputum smear microscopy remains the most widely available pulmonary TB diagnostic tool particularly in resource limited settings. A highly sensitive diagnostic with minimal infrastructure, cost and training is required.
View Article and Find Full Text PDF