A SUPPORT VECTOR-BASED PREDICTIVE MODEL TO REVEAL THE RELATIONSHIPS AMONG ANTIBODY FEATURES AND THEIR EFFECTIVE FUNCTIONS AGAINST HIV

Despite 4 decades’ effort, an effective HIV-1 vaccine has not been produced owing to the inevitable antigenic diversity of the virus and millions of people around the world have lost their lives due to HIV. Increasing the knowledge of adaptive immune response to vaccination would ultimately lead to an effective HIV cure. Antibodies, which are responsible for protection and fighting against antigens, are vital parts of immune system response. In order to identify discriminative antibodies, which provide protection against HIV, and to disclose the associations between antibody features and their functional outcomes, computational methods, such as feature selection, regression and classification can be used to construct predictive models. Here we used our unsupervised K-Means Based Feature Selection (KBFS) method which is presented in our previous study, to identify functional antibodies that fight against HIV. The accuracy results for the proposed KBFS framework are compared with those presented in a recent study and are also compared with results from four different state-of-the-art unsupervised feature selection methods, namely MCFS, InFS, LapFS, and SPFS, along with the entire feature set. Then, support vector based systems are utilised to predict the associations between antibody features and their functional activities, namely gp120-specific antibody dependent cellular phagocytosis (ADCP), antibody dependent cellular cytotoxicity (ADCC) and cytokine release activities on RV144 vaccine recipients. Pearson Correlation Coefficient (PCC) metric is used to evaluate the prediction accuracy of the predictive models and to be consistent with the previous study. Our SVR based KBFS framework presented higher accuracy than the original study by improving prediction performance 16% for ADCP assay, 200% for the ADCC assay

A Novel Methodology for Isolating Broadly Neutralizing HIV-1 Human Monoclonal Antibodies

Abstract also published in AIDS Research and Human Retroviruses. November 2013, 29(11): A-53. doi:10.1089/aid.2013.1500Poster presentationpublished_or_final_versio

Elicitation of broadly neutralizing HIV-1 antibodies by guiding the immune responses using primary and secondary immunogens

Abstract also published in AIDS Research and Human Retroviruses. November 2013, 29(11): A-44. doi:10.1089/aid.2013.1500Poster presentationpublished_or_final_versio

Defining the human mucosal CD4+ T cell and Mononuclear Phagocyte landscape by high parameter technologies

Tissue resident mononuclear phagocytes (MNP) are among the first immune cells that sexually transmitted pathogens encounter during transmission. These antigen presenting cells rapidly endocytose pathogens and then interact with CD4+ T cells to initiate adaptive immunity. In the case of HIV, the virus can be transferred from MNP to infect CD4+ T cells which are the primary target cell in which HIV undergoes replication. These MNP:CD4+ T cell interaction were originally believed to occur in lymph nodes but there is now an increasing body of evidence that this occurs within tissue at the site of transmission. There has been recent interest in defining the phenotype and the role of CD4+ TRMs in diseases. In HIV, CD4+ TRM have been shown to be a major target for productive and latent infection in the cervix. However, there are limited investigations into the CD4+ T cell landscape in other genital tissues. In this thesis, we optimised the enzymatic digestion process to maintain the cells in their physiological status. We have designed, optimised and implemented a 24-color flow cytometry panel to characterise T cells by memory, residency, activation. CD127 is known to be enriched on TRM. It is also a marker used in blood to identify regulatory T cells by surface expression. By preventing the enzymatic cleavage of surface markers during tissue digestion, we were able to identify a CD127+FOXP3+ T cell subset. We find its expression is dichotomous with TIGIT expression. The CD127+ Tregs express markers that are associated with TRM. Lastly, we examined the mononuclear phagocyte and CD4+ T cell landscape in human anogenital mucosa by single cell RNA sequencing (sc-RNAseq). We apply scRNA-Seq to conclude that Langerhans cells are not the only cells within the stratified epidermal layer of tissues, as the latter also contain conventional DC2 (cDC2). Further, we examine tissue pDCs and Axl+Siglec6+ DCs (ASDCs) by RNA sequencing and compare these to their counterparts in blood