Toward relevant measures of performance to manage complexity in inclusive development projects

The 2030 Agenda on Sustainable Development advocates for innovation for inclusive development. It is a fundamental issue to make progress within South African and globally. When one considers how to improve on the lack of success we have had so far, there are many areas of possible focus. This study looks at the management of innovation for inclusive development projects. These projects are complex. They harness science, technology and innovation to achieve a more inclusive and sustainable society. Their execution remains challenging despite models and tools to manage project complexity. The study focusses on how complexity exerts an influence on the management of these projects. It concurs with the literature that time, cost, and scope are inadequate measures on their own to assess complex project management performance. It seeks relevant measures of performance that can expand the triple constraint model to deal with complexity. To build a theory on the issues of concern, I use the lens of a project as a complex and adaptive temporary organisation. My qualitative study focuses on five projects within the Department of Science and Innovation in South Africa. It collects data from project management personnel, users and sponsors involved in these projects. The informants assist me in understanding the practise and processes of project management organisation and subsequent performance management. The study collects secondary data from various archival records. It uses the Gioia approach to analyse and interpret the data systematically and rigorously. The study contributes to complex project management theory, an evolving field. It expands existing knowledge by demonstrating how complexity influences the organisation of project management. It highlights how the plurality of stakeholders influences the definition and prioritisation of project goals. The prioritisation informs the allocation of resources, a task that is laden with conflict. The stakeholders establish a temporary organisation. The organisation has a unique identity, defined by the collective values of the stakeholders. Its governance is flexible, inclusive and responsive and embraces Ubuntu. Flexibility enhances its response to fluid and unpredictable changes in its context. The study underscores that learning is critical to the continuous improvement of the management of these projects. The stakeholders must recognise different ways of knowing to learn from each other. The findings stress technology appropriateness and its influence on organising project management. Technology itself might be exclusionary and marginalise other stakeholders within the temporary organisation. It shows the link between project management organisation and performance measurement. It highlights how complexity influences the selection of measures of performance. It proposes a four-dimensional model to expand the triple constraint measures. The dimensions are process, scope, context and good governance. The findings recommend further research to 2 understand how complexity influences the management of innovation for inclusive development projects

From practice to policy : a critical study of the perceptions and use of the female condom by women in Durban.

M.A. University of KwaZulu-Natal, Durban 2012.The study aims to probe the perceptions and experiences of using female condoms for women living in Durban. The study probes these perceptions and experiences within the embedded socio-cultural and gendered dynamics that influence, not only the perception and understanding of the female condom, but their gendered use as well. The study was premised on the understanding that female condoms or FCs are a ‘female initiated’ prevention method in preventing unplanned pregnancy, and most importantly in protecting against STIs and HIV/AIDS. The study also assumed that, given the feminized face of the AIDS pandemic, FCs could potentially be an empowering contraceptive tool with which women can exercise control over their own bodies and some control within their sexual relationships; negotiating safer sex, preventing pregnancy and the transmission of STIs like HIV. Mixed methods were used to collect data, using methodological tools such as a questionnaire, focus groups and in-depth interviews with participants from Chatsworth, Durban Central, Inanda, Lamontville, and Wentworth

Prospects for passive immunity to prevent HIV infection.

CAPRISA, 2017.Abstract available in pdf

South African HIV-1 Subtype C Transmitted Variants With A Specific V2 Motif Show Higher Dependence On aα4β7 For Replication

Background: The integrin aα4β7 mediates the trafficking of immune cells to the gut associated lymphoid tissue (GALT) and is an attachment factor for the HIV gp120 envelope glycoprotein. We developed a viral replication inhibition assay to more clearly evaluate the role of aα4β7 in HIV infection and the contribution of viral and host factors. Results: Replication of 60 HIV-1 subtype C viruses collected over time from 11 individuals in the CAPRISA cohort were partially inhibited by antibodies targeting aα4β7. However, dependence on aα4β7 for replication varied substantially among viral isolates from different individuals as well as over time in some individuals. Among 8 transmitted/founder (T/F) viruses, aα4β7 reactivity was highest for viruses having P/SDI/V tri-peptide binding motifs. Mutation of T/F viruses that had LDI/L motifs to P/SDI/V resulted in greater aα4β7 reactivity, whereas mutating P/SDI/V to LDI/L motifs was associated with reduced aα4β7 binding. P/SDI/V motifs were more common among South African HIV subtype C viruses (35%) compared to subtype C viruses from other regions of Africa

Infection pre-Ad26.COV2.S-vaccination primes greater class switching and reduced CXCR5 expression by SARS-CoV-2-specific memory B cells

Neutralizing antibodies strongly correlate with protection for COVID-19 vaccines, but the corresponding memory B cells that form to protect against future infection are relatively understudied. Here we examine the effect of prior SARS-CoV-2 infection on the magnitude and phenotype of the memory B cell response to single dose Johnson and Johnson (Ad26.COV2.S) vaccination in South African health care workers. Participants were either naïve to SARS-CoV-2 or had been infected before vaccination. SARS-CoV-2-specific memory B-cells expand in response to Ad26.COV2.S and are maintained for the study duration (84 days) in all individuals. However, prior infection is associated with a greater frequency of these cells, a significant reduction in expression of the germinal center chemokine receptor CXCR5, and increased class switching. These B cell features correlated with neutralization and antibody-dependent cytotoxicity (ADCC) activity, and with the frequency of SARS-CoV-2 specific circulating T follicular helper cells (cTfh). Vaccination-induced effective neutralization of the D614G variant in both infected and naïve participants but boosted neutralizing antibodies against the Beta and Omicron variants only in participants with prior infection. In addition, the SARS-CoV-2 specific CD8+ T cell response correlated with increased memory B cell expression of the lung-homing receptor CXCR3, which was sustained in the previously infected group. Finally, although vaccination achieved equivalent B cell activation regardless of infection history, it was negatively impacted by age. These data show that phenotyping the response to vaccination can provide insight into the impact of prior infection on memory B cell homing, CSM, cTfh, and neutralization activity. These data can provide early signals to inform studies of vaccine boosting, durability, and co-morbidities

Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection.

CAPRISA, 2016.Abstract available in pdf

Broadly neutralizing antibody specificities detected in the genital tract of HIV-1 infected women.

CAPRISA, 2016.Abstract available in PDF file.

CD8+ T cell breadth and ex vivo virus inhibition capacity distinguish between viremic controllers with and without protective HLA class I alleles.

CAPRISA, 2016.Abstract available in PDF file

Structure of an N276-dependent HIV-1 neutralizing antibody targeting a rare V5 glycan hole adjacent to the CD4 binding site.

CAPRISA, 2016.Abstract available in pdf

Shared N417-dependent epitope on the SARS-CoV-2 Omicron, Beta, and Delta Plus variants

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, several variants of concern (VOCs) have arisen which are defined by multiple mutations in their spike proteins. These VOCs have shown variable escape from antibody responses and have been shown to trigger qualitatively different antibody responses during infection. By studying plasma from individuals infected with either the original D614G, Beta, or Delta variants, we showed that the Beta and Delta variants elicit antibody responses that are overall more cross-reactive than those triggered by D614G. Patterns of cross-reactivity varied, and the Beta and Delta variants did not elicit cross-reactive responses to each other. However, Beta-elicited plasma was highly cross-reactive against Delta Plus (Delta+), which differs from Delta by a single K417N mutation in the receptor binding domain, suggesting that the plasma response targets the N417 residue. To probe this further, we isolated monoclonal antibodies from a Beta-infected individual with plasma responses against Beta, Delta+, and Omicron, which all possess the N417 residue. We isolated an N417-dependent antibody, 084-7D, which showed similar neutralization breadth to the plasma. The 084-7D MAb utilized the IGHV3-23*01 germ line gene and had somatic hypermutations similar to those of previously described public antibodies which target the 417 residue. Thus, we have identified a novel antibody which targets a shared epitope found on three distinct VOCs, enabling their cross-neutralization. Understanding antibodies targeting escape mutations, such as K417N, which repeatedly emerge through convergent evolution in SARS-CoV-2 variants, may aid in the development of next-generation antibody therapeutics and vaccines. IMPORTANCE : The evolution of SARS-CoV-2 has resulted in variants of concern (VOCs) with distinct spike mutations conferring various immune escape profiles. These variable mutations also influence the cross-reactivity of the antibody response mounted by individuals infected with each of these variants. This study sought to understand the antibody responses elicited by different SARS-CoV-2 variants and to define shared epitopes. We show that Beta and Delta infections resulted in antibody responses that were more cross-reactive than the original D614G variant, but they had differing patterns of cross-reactivity. We further isolated an antibody from Beta infection which targeted the N417 site, enabling cross-neutralization of Beta, Delta+, and Omicron, all of which possess this residue. The discovery of antibodies which target escape mutations common to multiple variants highlights conserved epitopes to target in future vaccines and therapeutics.The South African Research Chairs Initiative of the Department of Science and Innovation, the National Research Foundation of South Africa, the SA Medical Research Council SHIP program and the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program.https://journals.asm.org/journal/jvihj2023ImmunologyInternal Medicin