South African Research Chairs Initiative Research Articles

HIV skews the SARS-CoV-2 B cell response towards an extrafollicular maturation pathway.

HIV infection dysregulates the B cell compartment, affecting memory B cell formation and the antibody response to infection and vaccination. Understanding the B cell response to SARS-CoV-2 in people living with HIV (PLWH) may explain the increased morbidity, reduced vaccine efficacy, reduced clearance, and intra-host evolution of SARS-CoV-2 observed in some HIV-1 coinfections. We compared B cell responses to COVID-19 in PLWH and HIV negative (HIV-ve) patients in a cohort recruited in Durban, South Africa, during the first pandemic wave in July 2020 using detailed flow cytometry phenotyping of longitudinal samples with markers of B cell maturation, homing, and regulatory features. This revealed a coordinated B cell response to COVID-19 that differed significantly between HIV-ve and PLWH. Memory B cells in PLWH displayed evidence of reduced germinal centre (GC) activity, homing capacity, and class-switching responses, with increased PD-L1 expression, and decreased Tfh frequency. This was mirrored by increased extrafollicular (EF) activity, with dynamic changes in activated double negative (DN2) and activated naïve B cells, which correlated with anti-RBD-titres in these individuals. An elevated SARS-CoV-2-specific EF response in PLWH was confirmed using viral spike and RBD bait proteins. Despite similar disease severity, these trends were highest in participants with uncontrolled HIV, implicating HIV in driving these changes. EF B cell responses are rapid but give rise to lower affinity antibodies, less durable long-term memory, and reduced capacity to adapt to new variants. Further work is needed to determine the long-term effects of HIV on SARS-CoV-2 immunity, particularly as new variants emerge. This work was supported by a grant from the Wellcome Trust to the Africa Health Research Institute (Wellcome Trust Strategic Core Award [grant number 201433/Z/16/Z]). Additional funding was received from the South African Department of Science and Innovation through the National Research Foundation (South African Research Chairs Initiative [grant number 64809]), and the Victor Daitz Foundation.

Divergence of Delta and Beta Variants and SARS-CoV-2 Evolved in Advanced HIV Disease into Two Serological Phenotypes

SARS-CoV-2 continues to evolve variants which escape antibody neutralization and have enhanced transmission. One variant may escape immunity elicited by another, and the Delta variant has been reported to escape Beta variant infection elicited immunity. Mapping the serological distance between current and emerging variants will likely guide design of vaccines which can target all variants. Here we mapped neutralization of SARSCoV-2 ancestral and Beta and Delta variant viruses by antibodies elicited by each variant in SARS-CoV-2 convalescent individuals. We also serologically characterized and mapped SARS-CoV-2 which evolved from an ancestral strain in prolonged infection in an immunosuppressed individual due to advanced HIV disease. Beta virus showed moderate (7-fold) and Delta virus slight escape from neutralizing immunity elicited by ancestral virus infection. In contrast, Delta virus had pronounced escape from Beta elicited immunity (12fold), and Beta virus even stronger escape from Delta immunity (34-fold). Evolved virus had 9-fold escape from ancestral immunity, 27-fold escape from Delta immunity, but was effectively neutralized by Beta immunity. We conclude that Beta and Delta variants are serologically distant, further than each is from ancestral virus. An example of SARS-CoV2 evolved during advanced HIV disease immune suppression is serologically close to Beta and far from Delta. These results suggest that SARS-CoV-2 is diverging into distinct serological phenotypes which may become serotypes, and that vaccines tailored to one variant may become vulnerable to infections with another. Funding: This study was supported by the Bill and Melinda Gates award INV-018944 (AS), National Institutes of Health award R01 AI138546 (AS), South African Medical Research Council awards (AS, TdO, PLM) and National Institutes of Health U01 AI151698 (WVV). PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the NRF (Grant No 9834). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Declaration of Interests: None to declare. Ethics Approval Statement: Nasopharyngeal and oropharyngeal swab samples and plasma samples were obtained from hospitalized adults with PCR-confirmed SARS-CoV-2 infection who were enrolled in a prospective cohort study approved by the Biomedical Research Ethics Committee at the University of KwaZulu–Natal (reference BREC/00001275/2020).

Biology of Invasive Plants 1. Pyracantha angustifolia (Franch.) C.K. Schneid

The South African Working for Water (WfW) Programme of the Department of Environmental Affairs: National Resource Management is acknowledged for providing funding. Funding for this work was also provided by the South African Research Chairs Initiative of the Department of Science and Technology; the Afromontane Research Unit, South African National Biodiversity Institute, Centre for Invasion Biology; and the National Research Foundation (NRF) of South Africa.

Early antiretroviral treatment of infants to attain HIV remission

BackgroundStudies in adults and children suggested that starting antiretroviral therapy (ART) soon after infection positively influences early events in HIV infection raising the possibility that remission may be achieved in some. MethodsWe designed an analytic treatment interruption (ATI) trial to test the hypothesis that a sizable minority of HIV-infected neonates who initiated ART <14 days of birth and maintained on ART would be able to maintain viral suppression when ART was withdrawn. To yield the target cohort for this trial, 73 HIV-infected neonates identified at one hospital in Johannesburg, South Africa, were initiated on ART <14 days of birth and maintained on ART tracking viral load (VL) decline and immune recovery (clinicaltrials.gov # NCT02431975). FindingsThree HIV-infected infants (4.1%) died and nine (12.3%) were lost to follow-up before 48 weeks of age. Of those surviving on study, 52.5% attained and sustained VL <50 copies/ml and half of these sustained CD4+ T-cell percentage >30% which were the primary entry criteria for the ATI trial. Proportions achieving ATI eligibility criteria were similar in the 46 infants starting ART <48 h (19.6%) to 27 infants starting 2–14 days (25.9%) (p = 0.567). InterpretationVery early ART on its own, using regimens available when the trial was designed, is insufficient to attain minimum entry criteria needed to justify our trial of ART interruption. Decisions about how quickly to start ART should be based on optimizing standard clinical outcomes rather than with the expectation that remission can be attained. FundingNICHD/NIAID (U01HD080441), South African Research Chairs Initiative of DST and NRF (South Africa).

Mycobacterium Tuberculosis Blood Stream Infection Prevalence, Diagnosis, and Mortality Hazard in HIV-Positive Adults: A Systematic Review and Meta-Analysis of Individual Patient Data

Background: The clinical and epidemiological significance of HIV-associated Mycobacterium tuberculosis blood stream infection (MTB-BSI) is incompletely understood. We hypothesised that MTB-BSI prevalence has been underestimated, that MTB-BSI independently predicts death, and sputum Xpert has suboptimal diagnostic yield for MTB-BSI. Methods: We conducted a systematic review and individual patient data (IPD) meta-analysis of studies performing routine mycobacterial blood-culture (TBBC), including HIV-positive adults aged ≥13-years with suspected tuberculosis. Predicted probabilities of MTB-BSI from mixed-effects modelling were used to estimate prevalence. Estimates of diagnostic yield of sputum (Xpert or culture if Xpert unavailable) and urinelipoarabinomannan for MTB-BSI were obtained by two-level random-effect meta-analysis, mortality hazard of MTB-BSI by mixed-effect Cox proportional-hazard modelling, and effect of treatment delay with propensity-score analysis. Findings 5751 patients met inclusion criteria. Predicted probability of MTB-BSI was 45% (95%CI 38-52%) for danger-sign positive tuberculosis inpatients with cohort median CD4 count of 76 cells/μL. Diagnostic yield of sputum was 77% (95%CI 63–87%), rising to 89% (95%CI 80-94%) when combined with urinelipoarabinomannan testing. MTB-BSI increased hazard of death before 30-days (aHR2·5, 95%CI 2·1–3·1). In a propensity-score matched cohort (n=630), mortality increased with treatment delay >4 days in MTB-BSI (OR 3·2, 95%CI 1·1–10·3). Interpretation: In critically-ill adults with HIV-tuberculosis, MTB-BSI is a very frequent manifestation of tuberculosis and strongly predicts mortality. Better diagnostic yield in patients with MTB-BSI can be achieved by parallel use of sputum-Xpert and urine-LAM. Treatment delay may increase mortality hazard. Funding Statement: This study was supported by Wellcome fellowships 109105z/15/a, 105165/Z14/A. Charlotte Schutz was funded by the South African Medical Research Council under the National Health Scholars Programme. Moshi, Tanzania research was supported by an International Studies on AIDS Associated Co-infections (ISAAC) award, a program funded by the US National Institutes of Health (NIH) (U01 AI062563). John A. Crump receives support from US NIH R01AI121378. Elizabeth L. Corbett is supported by a Wellcome trust senior fellowship in clinical science (WT200901). Gary Maartens was supported in part by National Research Fund incentive funding (UID: 85810). Susan E. Dorman was supported by contract #HHSN2722000900050C and grant K24AI104830 (to SED), both from the US National Institutes of Health. Douglas Wilson was supported by BMS Secure the Future. Graeme Meintjes was supported by the Wellcome Trust (098316 and 203135/Z/16/Z), the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (Grant No 64787), NRF incentive funding (UID: 85858) and the South African Medical Research Council through its TB and HIV Collaborating Centres Programme with funds received from the National Department of Health (RFA# SAMRC-RFA-CC: TB/HIV/AIDS-01-2014). Declaration of Interests: David Alland is on the Scientific Advisory Board of Specific Technologies and receives a portion of the licensing income paid by Cepheid to Rutgers University for sales of the Xpert Ultra assay. Neil Martinson has received institutional grants for collection of specimens for Roche and Becton Dickinson, and from Pfizer for assessing incident pneumonia. All other authors declare no competing interests. Ethics Approval Statement: PROSPERO registration: CRD42016050022.

Examination of High-Porosity Activated Carbon Obtained from Dehydration of White Sugar for Electrochemical Capacitor Applications

The South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa under Grant no. 61056.

Expanding the Borders of Common Article 3 in Non-International Armed Conflicts: Amending Its Geographical Application Through Subsequent Practice?

The South African Research Chairs Initiative of the Department of Science and Technology and the National Research Foundation of South Africa (Grant no. 98338).

Cycling and floating performance of symmetric supercapacitor derived from coconut shell biomass

This work present two-step synthesizes route to low-cost mesoporous carbon from coconut shell. The electrochemical characterization of the coconut shell based activated carbon (CSAC) material as electrode for supercapacitor showed a specific capacitance of 186 F g-1, energy density of ∼11 Wh kg-1 and power density of 325 W kg-1 at a 0.5 A g-1 with an excellent stability after floating for 100 h and cycling for 10000 cycles in polymer gel electrolyte. The CSAC showed very good potential as a stable material for supercapacitors desirable for high power applications.

Activated carbon derived from tree bark biomass with promising material properties for supercapacitors

The South African Research Chairs Initiative of the Department of Science and Technology, Republic of South Africa and National Research Foundation of South Africa (Grant no. 97994).

Synthesis of 3D porous carbon based on cheap polymers and graphene foam for high-performance electrochemical capacitors

South African Research Chairs Initiative (SARChi) in Carbon Technology and Materials of the Department of Science and Technology (DST) and the National Research Foundation (NRF). University of Pretoria.

Chemical–structural properties of South African bituminous coals: Insights from wide angle XRD–carbon fraction analysis, ATR–FTIR, solid state 13 C NMR, and HRTEM techniques

South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Chair Grant No.: 86880, UID 85643, Grant No.: 85632)