Research Articles (Immunology)

Permanent URI for this collectionhttp://hdl.handle.net/2263/1864

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Humoral and cellular immunogenicity of COVID-19 vaccine boosters in participants with advanced HIV disease
Nesamari, Rofhiwa; Crowther, Carol; Chiveto, Dexter Tadiwanashe; Pillay, Thanusha; Kgagudi, Prudence; Shusha, Nomcebo; Manamela, Nelia; Steel, Helen Carolyn; Van der Mescht, Mieke Adri; Slingers, Nevilene; Davids, Lee-Ann; Tshabalala, Khanyisile; Ueckermann, Veronica; Seocharan, Ishen; Reddy, Tarylee; Richardson, Simone I.; Moyo-Gwete, Thandeka; Abdullah, Fareed; Moore, Penny L.; Rossouw, Theresa M. (Elsevier, 2026-02)
BACKGROUND : People living with HIV (PLWH) who experience advanced immunosuppression are susceptible to severe COVID-19 and demonstrate compromised vaccine responses due to low CD4 counts and uncontrolled HIV viral load. Although vaccine boosters enhance immunity in the general population, their immunogenicity in individuals with advanced HIV remains inadequately characterised. METHODS : This study evaluated the humoral and cellular immunogenicity of COVID-19 vaccine boosters in 41 individuals with advanced HIV at baseline and 4 weeks post-vaccination. Binding antibodies, neutralising antibodies, antibody-dependent cellular cytotoxicity (ADCC), as well as spike-specific CD4+ and CD8+ T-cell responses were quantified and characterised. RESULTS : Booster vaccination was found to increase binding antibody titres (8.0-fold) and neutralising activity (3.9-fold), even among participants with CD4 counts <100 cells/mm³, although absolute responses remained lower than the controls. ADCC activity also modestly increased post-vaccination (2.1-fold). Spike-specific CD4+ T-cell responses increased in magnitude (0.001% to 0.160%, p=0.0001) and responder frequency (49% to 83%, p=0.0167) post-vaccination, while CD8+ T-cell responses remained low. Compared to the controls, PLWH had similar magnitudes of spike-specific CD4+ T-cell responses but significantly lower CD8+ T-cell responses. CONCLUSION : COVID-19 vaccine boosters enhance immunity in PLWH, however, the responses remain suboptimal compared to immunocompetent individuals, emphasising the need for tailored vaccination strategies. HIGHLIGHTS • COVID-19 booster vaccination increased binding and neutralising antibodies in PLWH. • PLWH with CD4 <100 cells/mm³ had lower antibody titres. • Spike-specific CD4⁺ T-cell responses increased after vaccination in PLWH. • CD8⁺ T-cell responses remained low compared to controls. • Findings support tailored vaccination strategies for advanced HIV.
Functional rescue and AI analysis of a human inactivating GPCR mutation using a small molecule
Das, Debajyoti; Wyatt, Amanda; Sivaprasad, Sarath; Wahl, Vanessa; Qiao, Sen; Ectors, Fabien; Moosa, Zulfiah Mohamed; Newton, Claire Louise; Fritz, Mario; Millar, Robert P.; Boehm, Ulrich (Springer, 2026-02)
G protein-coupled receptors (GPCRs) carry out the majority of cellular transmembrane signaling. Many pathologies have underlying GPCR mutations, most of which cause misfolding and GPCR cell surface trafficking failure. Large libraries of existing small molecule GPCR ligands could be repurposed as pharmacological chaperones (PCs) which restore mutant GPCR folding and function, presenting an exciting alternative to complex gene repair, yet such in vivo studies are limited. Therefore, as proof-of-concept, we use one such known ligand/PC, Org42599/Org43553, to show functional rescue in mice bearing an inactivating human luteinizing hormone receptor (LHR) mutation. Mutant males had delayed puberty and Leydig cell LHR signaling impairment, however, fertility was unaffected. Mutant females had irregular estrous cycles, anovulation, abrogated ovarian LHR signaling, and complete infertility. PC treatment of mutant females restored LH signaling and estrous cyclicity. To characterize treatment efficacy, we developed an AI algorithm that reliably identified inherent differences among experimental groups, enabling functional analysis of the treatment effect in vivo. Our data set the stage to integrate AI analysis with GPCR-targeting PC molecules to treat diverse GPCR-based diseases.
Translational human and equine regenerative medicine in musculoskeletal conditions
Bosman, Lisa Marie; Logan, Murray Glen; Miszewski, A.; Pepper, Michael Sean (Elsevier, 2026-03)
Translational regenerative medicine, integrating human and veterinary approaches within the “One Health” framework, increasingly uses horses as models for human musculoskeletal conditions due to shared anatomical and functional features. Osteoarthritis and tendon disorders affect both species, often resulting from high-impact or repetitive strain activities. Regenerative medicine offers therapeutic opportunities by promoting tissue repair and modulating inflammation. Cellular orthobiologics such as mesenchymal stromal/stem cells (MSCs) show promise for treating osteoarthritis and tendon injuries in humans and horses, while non-cellular orthobiologics—including platelet-rich plasma, interleukin-1 receptor antagonist protein, and alpha-2 macroglobulin—provide growth factors and anti-inflammatory molecules that support tissue regeneration. However, challenges remain, including variable product manufacture, inconsistent MSC isolation and characterization protocols (particularly in equine applications), and regulatory or public scepticism toward these therapies. Standardized production methods and improved clinical integration are needed. Combinatory use of cellular and non-cellular orthobiologics offers strong translational potential to improve musculoskeletal repair across species. HIGHLIGHTS • Equine–human musculoskeletal research aligns with One Health principles. • Cost, lifespan, and ethics limit horses as human translational models. • Standardized orthobiologic production protocols are needed to improve reliability. • Regulatory and public scepticism continue to hinder adoption of cell therapies. • New technologies and combined therapies may improve clinical outcomes.
Pharmacokinetics and bioavailability of pembrolizumab with berahyaluronidase alfa for subcutaneous administration in participants with advanced or metastatic solid tumors : the phase 1 study 3475A-C18
Cohen, Graham L.; Coetzee, Corlia; Walton, Cathryn A.; Torras, Oscar Reig; Cho, Byoung Chul; McAdam, Georgina; Rojas, Carlos I.; Rodríguez, Laura Medina; Papai, Zsuzsanna; Chan, Sze W.; Rapoport, Bernardo Leon; Caglevic, Christian; Weber, Patricio Yanez; Takahashi, Toshiaki; Kurata, Takayasu; Song, Gina; Cohen, Julia W.; Akala, Omobolaji O.; Khanyile, Richard (Elsevier, 2025-11)
BACKGROUND : MK-3475A is pembrolizumab with berahyaluronidase alfa for subcutaneous administration (pembrolizumab SC). The phase 1 study 3475A-C18 (NCT05017012) assessed the pharmacokinetic and safety profiles of pembrolizumab SC. METHODS : The study had 4 arms that enrolled participants with unresectable or advanced melanoma (arms 1, 2, and 4), metastatic NSCLC (arms 1–3), or advanced or metastatic RCC (arms 1 and 2). Participants received pembrolizumab SC 650 mg Q6W at solution strengths of 165 mg/mL (arms 1 and 3), 130 mg/mL (arm 2), or pembrolizumab SC 395 mg Q3W at 165 mg/mL (arm 4). Key endpoints included pembrolizumab SC bioavailability, pharmacokinetics, immunogenicity, and safety and tolerability. RESULTS : 140 participants received study treatment. Across all arms, mean bioavailability of pembrolizumab SC was 61 % (95 % CI, 58 %single bond64 %; CV%, 22.4 %) and absorption rate was 0.30/day (95 % CI, 0.28–0.32/day; CV%, 43.7 %). Pharmacokinetic exposure, bioavailability, and absorption rate did not differ meaningfully with pembrolizumab SC by solution strength. Treatment-emergent anti-drug antibodies against pembrolizumab and berahyaluronidase occurred in 1 % and 2 % of participants, respectively. Injection site AEs with pembrolizumab SC occurred in 16 % of participants; all were grade 1/2 in severity. Immune-mediated AEs occurred in 41 % of participants in arms 1–3 and 18 % of participants in arm 4. CONCLUSION : Results from study 3475A-C18 informed selection of pembrolizumab SC 790 mg Q6W at 165 mg/mL for further clinical development to ensure that all patients have the appropriate pembrolizumab exposure to derive expected clinical benefit. Arm 4 results provided key clinical data supporting the pembrolizumab SC 395 mg Q3W dosing regimen.
An epigenetic perspective on neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy
Mistry, Priyal; Mellet, Juanita; Durandt, Chrisna; Smuts, Izelle; Pepper, Michael Sean (BioMed Central, 2025-12-08)
Neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy (NESHIE) is a neurological disorder caused by oxygen deprivation and limited blood flow to a neonate's brain. Although various antenatal and perinatal factors have been identified, their precise role in NESHIE pathogenesis remains unclear. The pathophysiology involves multiple molecular pathways that can be explored using a multi-omics approach, including epigenetics. Epigenetics involves heritable changes in gene expression without altering the DNA sequence, encompassing chemical modifications to DNA and histone proteins, as well as changes mediated by non-coding RNAs (ncRNAs). These epigenetic changes regulate gene expression and can be influenced by environmental factors, offering crucial insights into gene regulation and disease mechanisms. This review examines the role of epigenetic mechanisms in NESHIE, focusing on the modulation of hypoxia-inducible factor-1 alpha (HIF-1α) and ncRNA during hypoxic conditions. Additionally, epigenetic-mediated foetal programming may shed light on how maternal and antenatal risk factors contribute to NESHIE susceptibility. Understanding these epigenetic signatures could advance biomarker discovery and the development of novel therapeutic strategies for NESHIE.
The implementation of small molecule agonists and antagonists to elucidate gonadotropin receptor structure, function and physiology
Dias, James A.; Newton, Claire Louise; Ulloa-Aguirre, Alfredo (Elsevier, 2026-05)
Pursuant to patient desires of alternatives to injectable gonadotropins, a plethora of attempts have identified, characterized, and demonstrated efficacy of small molecules that activate (agonists) gonadotropin receptors. Discoveries have also been made of small molecule gonadotropin receptor inhibitors (antagonists), which have potential as useful alternatives to steroid hormone-based contraception. Implementation of these small molecules in advanced testing systems not necessarily used in screening, which identified lead compounds, has yielded a bounty of wonders. It is likely that a richer understanding of the role of signaling platforms and conformation-dependent molecular assemblies are likely to emerge. Several small molecule agonists have been observed to function as conformational boosters that can rescue receptor trafficking defects, or initiate internalization of receptors without bound hormone. Still others have revealed insights into the role of molecular platforms in persistent signaling. Unexpectedly, such antagonists, like molecular scalpels, can ablate certain signaling pathways and not others leading to discovery of biased signaling in gonadotropin receptors. That seminal observation has led to studies of nuanced signaling and, consequently, nuanced gene expression. Gonadotropin receptor structure-based design for better specificity and potency of agonists and antagonists has been provided by new cryo-EM structures of the gonadotropin receptors, demonstrating proof of concept. Structural determination of downstream supramolecular assemblies will be necessary to validate and fully understand these complicated receptors and how their interaction with other proteins and when occupied by hormone and allosteric modulators, nuances their actions and, ultimately, fertility. HIGHLIGHTS • Small molecules that bind to gonadotropin receptors may activate or inhibit receptor function. • The majority of small molecules for the gonadotropin receptors are allosteric compounds. • Some agonists and antagonists exhibit biased signaling and/or promote correct folding and trafficking defects. • Though not in clinical use, they have helped decode receptor structure and function. • Gonadotropin receptor small molecules offer alternatives for more precise and nuanced fertility modulation.
Immunopathogenesis and therapeutic implications in basal cell carcinoma : current concepts and future directions
Steel, Helen Carolyn; Rossouw, Theresa M.; Anderson, Ronald; Anderson, Lindsay; Van Tonder, Daniel; Smit, Teresa; Rapoport, Bernardo Leon (MDPI, 2025-10-25)
This review is focused on understanding the reasons why basal cell carcinoma (BCC), the most common, increasingly prevalent cancer, is classified as an “immune excluded” malignancy. It is, despite manifesting one of the highest tumor mutational burdens of any solid human malignancy, considered to be a biomarker of enhanced tumor immunogenicity and efficacy of tumor-targeted immunotherapy. Following a brief clinical overview, the balance of the review addresses important translational issues based on recent insights into the mechanisms underpinning immune exclusion/evasion in BCC. These include, firstly, the role of infectious agents and non-infectious potential causes of predisposition for and/or exacerbation of disease development and progression. Secondly, an overview of existing and emerging novel therapeutic strategies to ameliorate immune exclusion in BCC based on targeting several key immunosuppressive mechanisms. These are (i) inappropriate activation of the hedgehog signaling pathway (HHSP) due to formation of key driver mutations; (ii) interference with the presentation of tumor-specific antigens/neoantigens to cytotoxic T-cells; (iii) attenuation of the influx of anti-tumor natural killer cells; (iv) the recruitment and activation of immune suppressive regulatory T-cells; and (v) localized and systemic immune dysfunction achieved via elevated levels of soluble co-inhibitory immune checkpoint proteins (ICPs). The final section is focused on current and emerging pharmacologic and immune-based therapies.
Increasing access to pediatric allogeneic hematopoietic stem cell transplantation in South Africa
Hendricks, Candice Laverne; Brittain, David; Davidson, Alan; Novitzky, Nicolas; Du Toit, Justin Rudolph; Thomson, Jackie; Reynders, David; Geel, Jennifer Ann; Naidu, Gita; Mellet, Juanita; Durandt, Chrisna; West, Erna; Ingram, Charlotte; Verburgh, Estelle; Pepper, Michael Sean (Wiley, 2026)
Current pediatric allogeneic hematopoietic stem cell transplantation (HSCT) services in South Africa do not meet the substantial demand in the country. The factors leading to this paucity are multifactorial, including a limited number of appropriate donors on our local registries, inadequate identification and referral of appropriate patients, long distances to travel to health facilities, socioeconomic inequality, and inadequate infrastructure and clinical expertise for the number of transplants required. We describe a model for a large HSCT unit that caters to insured and uninsured patients in order to ensure equitable access, and which is in line with the WHO health system building blocks. The scale at which transplantation will be achieved will allow for the development of local skills and expertise, which can be decentralized in the future to further improve HSCT access.
Biofiltration, seasonality, and distribution system factors influence nitrifier communities in a full-scale chloraminated drinking water system
Potgieter, Sarah; Oosthuizen-Vosloo, Solize; Langenfeld, Kathryn; Dowdell, Katherine S.; Vedrin, Matthew; Lahr, Rebecca; Pinto, Ameet J.; Raskin, Lutgarde (Elsevier, 2026-03)
Nitrification in chloraminated drinking water systems has been widely studied, although limited information is available on the role of biofiltration in shaping the nitrifier communities within drinking water distribution systems (DWDS). Additionally, the co-occurrence of comammox and canonical nitrifiers in drinking water systems remains unclear. This study investigates how biofiltration shapes nitrifier communities in a full-scale drinking water system where chloramine is a secondary disinfectant, and biofilters are backwashed with chloraminated water. Samples were collected monthly for one year from biofilter effluent, finished water, and three DWDS sites with varying water ages, water quality, and nitrite concentrations. Nitrifier abundances were quantified using droplet digital PCR, which showed contrasting temporal trends between the ammonia-oxidizing bacteria amoA gene and both nitrite-oxidizing bacteria 16S rRNA gene and comammox amoB gene abundances. Genome-resolved quantitative metagenomics revealed Nitrosomonas cluster 6a species, canonical Nitrospira species, and Nitrospira-like comammox species as the dominant nitrifiers. The same populations were detected in biofilter effluent and across DWDS sites, indicating that biofilter operation contributed to the persistence of nitrifiers in the DWDS. Further, DWDS site-specific factors, such as water age and disinfectant degradation, influenced the presence and abundance of individual nitrifier populations. These findings advance our understanding of how upstream treatment processes influence microbial community structure and nitrifier persistence in full-scale chloraminated DWDSs, and highlight the importance of considering biofilter operation, alongside disinfection practices, within integrated nitrification control strategies. HIGHLIGHTS • Seasonal and spatial factors shaped nitrifier dynamics and nitrite accumulation. • Nitrosomonas cluster 6a, Nitrospira, and comammox co-occurred throughout the system. • Nitrifier MAGs in the biofilter effluent persisted through the distribution system. • Distribution system water age influenced the spatial patterns of Nitrosomonas MAGs. • Comammox showed seasonal variation and persisted post-chloramination.
Folding, misfolding, and regulation of intracellular traffic of G protein-coupled receptors involved in the hypothalamic–pituitary–gonadal axis
Ulloa-Aguirre, Alfredo; Anderson, Ross Calley; Zariñán, Teresa; Gutiérrez-Sagal, Rubén; Jardón-Valadez, Eduardo; Newton, Claire Louise (Wiley, 2025)
BACKGROUND : G protein-coupled receptors are a large and functionally diverse family of membrane receptors involved in a number of biological processes. Like other proteins, G protein-coupled receptors need to be properly folded in order to traffic to the plasma membrane and interact with agonist. OBJECTIVE : Herein, we briefly review the process of folding and intracellular traffic of G protein-coupled receptors, with a focus on the gonadotropin-releasing hormone receptor and the gonadotropin receptors, whose variants can lead to misfolding, loss of plasma membrane trafficking and eventually to different forms of hypogonadism. RESULTS AND DISCCUSSION : Pathogenic variants of G protein-coupled receptors may provoke loss-of-function of the receptor protein, thereby leading to disease. The presence of a stringent cellular quality control system promotes proper protein folding compatible with endoplasmic reticulum export and concomitantly prevents unfolded proteins accumulating within the cell. Molecular chaperones and companion factors are key elements of the quality control system that maintain the integrity of the proteostasis network by regulating, at different levels folding and assembly of nascent proteins and by promoting degradation of defective conformers, preventing aggregation and toxic accumulation. Due to the importance of the concept of molecular chaperoning in protein folding, pharmacoperone drugs emulating the role of endogenous chaperones as stabilizers of protein conformation currently represent a novel therapeutic opportunity for rescuing misfolded receptors and treating different diseases due to protein misfolding. CONCLUSIONS : In vitro and in vivo studies in experimental animals and in humans have provided proof-of-principle of the beneficial effects of pharmacoperone drugs in modifying the course of human disease due to misfolding of G protein-coupled receptors.
Artificial intelligence for HIV care : a global systematic review of current studies and emerging trends
Ngcobo, Sanele; Madela-Mntla, Edith; Shock, Jonathan; Louw, Murray; Mbonambi, Linda; Serite, Thato; Rossouw, Theresa M. (Wiley, 2025-09)
INTRODUCTION : Artificial intelligence (AI) and, in particular, machine learning (ML) have emerged as transformative tools in HIV care, driving advancements in diagnostics, treatment monitoring and patient management. The present review aimed to systematically identify, map and synthesize studies on the use of AI methods across the HIV care continuum, including applications in HIV testing and linkage to care, treatment monitoring, retention in care, and management of clinical and immunological outcomes. METHODS : A comprehensive literature search was conducted across databases, including PubMed and ProQuest Central, Scopus and Web of Science, covering studies published between 2014 and 2024. The review followed PRISMA guidelines, screening 3185 records, of which 47 studies were included in the final analysis. RESULTS : Forty-seven studies were grouped into four thematic areas: (1) HIV testing, AI models improved diagnostic accuracy, with ML achieving up to 100% sensitivity and 98.8% specificity in self-testing and outperforming human interpretation of rapid tests; (2) Retention in care and virological response, ML predicted clinic attendance, viral suppression and virological failure (72-97% accuracy; area under the curve up to 0.76), enabling early identification of high-risk patients; (3) Clinical and immunological outcomes, AI predicted disease progression, immune recovery, comorbidities and HIV complications, achieving up to 97% CD4 status accuracy and outperforming clinicians in tuberculosis diagnosis; (4) Testing and treatment support, AI chatbots improved self-testing uptake, linkage to care and adherence support. Methods included random forests, neural networks, support vector machines, deep learning and many others. DISCUSSION : AI has the potential to transform HIV care by improving early diagnosis, treatment adherence and retention in care. However, challenges such as data quality, infrastructure limitations and ethical considerations must be addressed to ensure successful implementation. CONCLUSIONS : AI has demonstrated immense potential to address gaps in HIV care, improving diagnostic accuracy, enhancing retention strategies and supporting effective treatment monitoring. These advancements contribute towards achieving the UNAIDS 95-95-95 targets. However, challenges such as data quality and integration into healthcare systems remain. Future research should prioritize scalable AI solutions tailored to high-burden, resource-limited settings to maximize their impact on global HIV care.
Triple-negative breast cancer at Helen Joseph Hospital : prevalence, age and imaging features
Zondi, Tsholofelo; Rubin, Grace; Benn, Carol-Ann; Gounden, Sharadini K. (AOSIS, 2025-10)
BACKGROUND : Triple-negative breast cancer (TNBC) is considered an aggressive subtype, defined by the absence of oestrogen, progesterone and HER2 receptors. It typically presents earlier and more aggressively. Limited data exist on its prevalence, age of onset and imaging features in South Africa. OBJECTIVES : This study aimed to assess the prevalence of TNBC at Helen Joseph Tertiary Hospital (HJTH), describe its histopathological features and explore trends in age at diagnosis and imaging patterns-including early-onset disease. METHOD : A retrospective review of 280 female patients with histologically confirmed breast cancer, diagnosed between January 2021 and December 2023, was conducted. Demographic, imaging and histopathology data were analysed using descriptive statistics and chi-square tests. RESULTS : The diagnosis of TNBC accounted for 17% (48/280) of all breast cancer cases in the cohort. The TNBC lesions typically measured 1-5 cm and showed nodal involvement in 73% of cases. Despite their aggressive biology, many TNBC lesions appeared circumscribed or only mildly irregular on imaging, mimicking benign masses. Among all the 280 breast cancer cases, 61% were high-grade. The mean Ki-67 index for TNBC was the highest at 52%, followed by HER2+ (39%), Luminal B (33%) and Luminal A (21%). Notably, some HER2+ and TNBC cases exhibited lower Ki-67 indices, highlighting heterogeneity within these subtypes. CONCLUSION : This study highlights the complexity of breast cancer presentation in a South African setting, particularly the discordance between tumour biology and imaging. CONTRIBUTION : These findings contribute local data on TNBC in an urban public healthcare context, supporting improved imaging awareness and clinical vigilance in resource-limited settings.
Heritable human genome editing in South Africa - time for a reality check
Ramsay, Michele; Pepper, Michael Sean; De Vries, Jantina; Mahomed, Safia; Flack-Davison, Eleni (South african Medical Association, 2025-02)
Referring to the third edition of the South African Ethics in Health Research Guidelines: Principles, Processes and Structures (the guidelines) dated May 2024, Baylis and Hasson assert that the guidelines support heritable human genome editing (HHGE), which allows for children conceived from ‘gene-edited’ cells to be born. On 7 November 2024, a news item appeared in Nature titled ‘Will South Africa become first country to accept controversial form of human genome editing?’ As South African (SA) scholars in the fields of genetics, biology, law and ethics, we wish to express our dismay that national and international audiences should be misled to believe that SA law accommodates or should be changed to allow for the clinical application of HHGE. What is at stake is not whether HHGE is permissible for research purposes in SA, but whether it is permissible to create live births.
Progress in advanced cellular and gene therapies in South Africa and barriers to patient access : a National Consortium paper on behalf of the BloodSA Cell and Gene Therapy working party
Hendricks, Candice Laverne; Viljoen, I.; Botes, M.; Brittain, D.; Mahlangu, J.; Verburgh, E.; Gerdener, T.; Herd, C.; Logan, Murray Glen; Marais, A.L.; Glatt, T.N.; Cockeran, R.; Poole, C.; Du Toit, J.; Pepper, Michael Sean (South african Medical Association, 2025-06)
The fields of molecular and cellular medicine have, in recent years, witnessed a great deal of progress globally, particularly in understanding disease pathogenesis and through the development of advanced cellular therapy products and gene therapies. Despite the transformative potential of these new therapies, low- and middle-income countries face significant barriers to their access. Advanced cellular therapy legislation in South Africa (SA) has not kept up with this fast-advancing field, and requires a fast-tracked renewal. Furthermore, the prohibitive cost of commercial therapies, including chimeric antigen receptor (CAR) T-cell products, and the lack of infrastructure, manufacturing and research capacity, must be addressed to make equitable patient access an achievable goal in our setting. To this end, a national cell and gene therapy consortium, comprising clinicians, clinician-scientists, scientists, legal experts, postgraduate students and representatives from industry, the national blood service and the pharmaceutical industry, was initiated. The mandate of this group is to aid the progression of advanced cellular therapies in SA, and the purpose of this article is to outline the progress that has been made. We will highlight the gaps in each core field of practice within this space, and provide a proposal for making these therapies more accessible in SA.
Addressing the limitations of the regulatory landscape in South Africa regarding advanced cell and gene therapies and related sectors involving human cells, tissues and organs
Viljoen, Ignatius M.; Pepper, Michael Sean (South african Medical Association, 2025-02)
Advanced cell-based and gene therapy products emerged during the 1990s as new health product categories for treating and curing previously untreatable or incurable conditions. These products are complex, diverse and therapeutically specific, requiring specialised regulatory frameworks. During the last three decades, several jurisdictions have constructed specific regulatory frameworks to ensure these products’ safety, clinical efficacy and quality. As these are new and disruptive products, these frameworks are continuously evolving. However, South Africa (SA)’s regulatory frameworks for medicines, human biological materials and genetically modified organisms have not kept pace with scientific and technological developments, leaving regulatory gaps. We briefly describe these novel products and their regulatory frameworks, and propose a way forward in SA.
Section on heritable human genome editing withdrawn from the National Health Research Ethics Council guidelines
Mahomed, Safia; Ramsay, Michèle; Pepper, Michael Sean; De Vries, Jantina; Flack-Davison, Eleni (South african Medical Association, 2025-08)
No abstract available.
Response to : In defence of South Africa’s National Health Research Ethics Council guidelines on heritable human genome editing
Ramsay, Michèle; Pepper, Michael Sean; De Vries, Jantina; Mahomed, Safia; Flack-Davison, Eleni (South african Medical Association, 2025-02)
No abstract available.
RSV : an overview of infection in adults
Feldman, Charles; Anderson, Ronald (BioMed Central, 2025-06-28)
BACKGROUND : Respiratory syncytial virus (RSV) infection was originally considered to be simply a disease of childhood. However, it has increasingly been recognized that the virus may also cause infection in adults. Furthermore, great strides have been made in understanding the clinical manifestations, as well as aspects of its management and prevention, requiring the need for greater awareness of the various aspects of this infection in adults. MAIN BODY : There are several potential reasons that RSV may have been overlooked in adults. Firstly, it was due to a lack of knowledge that this infection could occur in this age group. Secondly, there was infrequent testing for RSV infection in adults, both for this reason and because RSV antigen testing in adults is less sensitive than in children. Thirdly, RSV diagnosis, therefore, required the performance of polymerase chain reaction (PCR) testing, which is both expensive and underutilized. Finally, there was also the belief at that time that if the infection was due to RSV, there was little one could do to about it in terms of treatment and/or prevention. More recently, however, enormous advances have been made particularly in the management and prevention of this infection. This manuscript, which is an extensive literature review, describes the modern understanding of the burden of infection, the clinical presentation, risk factors, immunopathogenesis, management, and prevention of RSV infections in adults. CONCLUSION : RSV virus is a common cause of respiratory tract infections in adults and advances in recent research have not only enhanced our knowledge of this infection but have led to the development of effective treatment and prevention of the infection.
Guest editorial
Van Niekerk, Andre (Allergy Society of South Africa, 2025-03)
Many short courses (bursts) of oral corticosteroids (OCS) are commonly prescribed for indicated and non-indicated conditions. These bursts are perceived to be safe and are usually given by prescription for less than 14 days at a time. The global corticosteroid market was USD 5.7 billion in 2023, and with a projected annual growth rate of 4.6% across all regions, reflects its widespread use. Published data of OCS use in South Africa are difficult to find, yet parents of children attending a clinic for immune deficiencies frequently report repetitive prescriptions.
The mechanism of action of oral corticosteroids in relation to short- and long-term-burst therapy
Cordier, Werner; Rossouw, Theresa M. (Allergy Society of South Africa, 2025-03)
Corticosteroids, potent anti-inflammatory agents, are broadly used in various inflammatory and immune-dependent pathologies, which include asthma. Through non-genomic and genomic mechanisms of action, corticosteroids reduce pro-inflammatory mediators while promoting anti-inflammatory molecule expression. Furthermore, in the context of asthma treatment, they also promote the expression of β2 adrenergic receptors which increase the therapeutic potential of β2-receptor agonists to promote bronchodilation. However, corticosteroids also precipitate a variety of adverse events which reduce the quality of life of patients and predispose them to further pathological alterations. Given the ubiquitous expression of the glucocorticoid receptor, alongside the non-genomic and genomic mechanisms of corticosteroids, a myriad interconnecting physiological processes are altered upon receptor modulation. Both long- and short-course treatment has been linked to immune suppression, metabolic and cardiovascular disease, cerebrovascular accidents, osteoporosis, ophthalmic disorders, pneumonia and mood disorders. Consequently, clinical decision-making should consider the potential risks involved in short- and long-term use of corticosteroids because pathophysiological changes may be precipitated in both.

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