Tandile Hermanus

National Health Laboratory Service

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Penny L. Moore

University of the Witwatersrand

Lynn Morris

Centre for the AIDS Programme of Research in South Africa

Thandeka Moyo-Gwete

University of the Witwatersrand

Prudence Kgagudi

South African Medical Research Council

Simone I. Richardson

University of the Witwatersrand

Nelia P. Manamela

University of the Witwatersrand

Carolyn Williamson

University of Cape Town

Nigel Garrett

Centre for the AIDS Programme of Research in South Africa

Wendy A. Burgers

Wellcome Centre for Infectious Diseases Research in Africa

Zanele Makhado

University of the Witwatersrand

Cooperative Institutions

University of Cape Town

University of the Witwatersrand

South African Medical Research Council

National Institute of Allergy and Infectious Diseases

National Institutes of Health

University of KwaZulu-Natal

National Health Laboratory Service

National Institute for Communicable Diseases

Fred Hutch Cancer Center

University of Washington

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

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

SSRN Electronic Journal (2021)

Sandile Cele Farina Karim Gila Lustig James Emmanuel San Tandile Hermanus

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).

Immune escape

10.2139/ssrn.3934612

Cite

Citations (1)

Heterologous Immunization with Improved HIV-1 Subtype C Vaccines Elicit Autologous Tier 2 Neutralizing Antibodies with Rapid Viral Replication Control After SHIV Challenge

Viruses (2025)

Gerald K. Chege Rosamund Chapman Alana Keyser Craig H. Adams Kealan Benn

We previously reported on HIV vaccines that elicited autologous Tier 2 neutralizing antibodies (nAbs) in rabbits. In the current study, we sought to establish a proof of concept that HIV vaccines using identical designs elicit Tier 2 nAbs in arhesus macaque (RM) model. DNA and MVA vaccines expressing SIV Gag and HIV-1 Env antigens were constructed, and in vitro expression was confirmed. A soluble envelope protein (gp140 Env) was expressed from a stable HEK293 cell line and purified using lectin affinity and size exclusion chromatography. The expression and secretion of SIV Gag and HIV-1 Env by the DNA and MVA vaccines was verified in vitro. Five RMs were inoculated with two DNA, followed by two MVA, and finally with two gp140 Env vaccines at weeks 0, 4, 8, 12, 20 and 28. Vaccine-induced T cell immunity was measured by IFN-γ ELISpot while nAbs were evaluated against MW965 (Tier 1A), 6644 (Tier 1B), autologous ZM109.5A and a closely-related ZM109.B4 (Tier 2) pseudovirions. Vaccinated RMs were challenged intrarectally with simian-human immunodeficiency virus (SHIV), four weeks after the final vaccination, as was an unvaccinated control group (n = 4). Following vaccination, all the animals developed moderate IFN-γ ELISpot responses after the DNA vaccinations which were boosted by the MVA vaccine. After the gp140 Env boost, all animals developed nAbs with peak median titres at 762 (MW965) and 263 (ZM109.5A). The vaccinated animals became infected after a similar number of challenges to the unvaccinated controls, and the resultant number of viral copies in the blood and the lymphoid tissues were similar. However, the duration of detectable viraemia in the vaccinated animals (median: 2 weeks) was shorter than the controls (median: 8.5 weeks). These data show that the vaccines elicited robust cellular and functional humoral immune responses that resulted in a quicker control of viraemia.

ELISPOT

Heterologous

HIV vaccine

AIDS Vaccines

10.3390/v17020277

Cite

Citations (0)

SARS-CoV-2 evolved during advanced HIV disease immunosuppression has Beta-like escape of vaccine and Delta infection elicited immunity

medRxiv (Cold Spring Harbor Laboratory) (2021)

Sandile Cele Farina Karim Gila Lustig James Emmanuel San Tandile Hermanus

Summary Characterizing SARS-CoV-2 evolution in specific geographies may help predict the properties of variants coming from these regions. We mapped neutralization of a SARS-CoV-2 strain that evolved over 6 months from the ancestral virus in a person with advanced HIV disease. Infection was before the emergence of the Beta variant first identified in South Africa, and the Delta variant. We compared early and late evolved virus to the ancestral, Beta, Alpha, and Delta viruses and tested against convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral, whereas late virus was similar to Beta, exhibiting vaccine escape and, despite pre-dating Delta, strong escape of Delta-elicited neutralization. This example is consistent with the notion that variants arising in immune-compromised hosts, including those with advanced HIV disease, may evolve immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections. Highlights A prolonged ancestral SARS-CoV-2 infection pre-dating the emergence of Beta and Delta resulted in evolution of a Beta-like serological phenotype Serological phenotype includes strong escape from Delta infection elicited immunity, intermediate escape from ancestral virus immunity, and weak escape from Beta immunity Evolved virus showed substantial but incomplete escape from antibodies elicited by BNT162b2 vaccination Graphical abstract

Immune escape

10.1101/2021.09.14.21263564

Cite

Citations (21)

Despite delayed kinetics, people living with HIV achieve equivalent antibody function after SARS-CoV-2 infection or vaccination

Frontiers in Immunology (2023)

Boitumelo M. Motsoeneng Nelia P. Manamela Haajira Kaldine Prudence Kgagudi Tandile Hermanus

The kinetics of Fc-mediated functions following SARS-CoV-2 infection or vaccination in people living with HIV (PLWH) are not known. We compared SARS-CoV-2 spike-specific Fc functions, binding, and neutralization in PLWH and people without HIV (PWOH) during acute infection (without prior vaccination) with either the D614G or Beta variants of SARS-CoV-2, or vaccination with ChAdOx1 nCoV-19. Antiretroviral treatment (ART)–naïve PLWH had significantly lower levels of IgG binding, neutralization, and antibody-dependent cellular phagocytosis (ADCP) compared with PLWH on ART. The magnitude of antibody-dependent cellular cytotoxicity (ADCC), complement deposition (ADCD), and cellular trogocytosis (ADCT) was differentially triggered by D614G and Beta. The kinetics of spike IgG-binding antibodies, ADCC, and ADCD were similar, irrespective of the infecting variant between PWOH and PLWH overall. However, compared with PWOH, PLWH infected with D614G had delayed neutralization and ADCP. Furthermore, Beta infection resulted in delayed ADCT, regardless of HIV status. Despite these delays, we observed improved coordination between binding and neutralizing responses and Fc functions in PLWH. In contrast to D614G infection, binding responses in PLWH following ChAdOx-1 nCoV-19 vaccination were delayed, while neutralization and ADCP had similar timing of onset, but lower magnitude, and ADCC was significantly higher than in PWOH. Overall, despite delayed and differential kinetics, PLWH on ART develop comparable responses to PWOH, supporting the prioritization of ART rollout and SARS-CoV-2 vaccination in PLWH.

Receptor–ligand kinetics

10.3389/fimmu.2023.1231276

Cite

Citations (6)

Potent and Broad Neutralization of HIV-1 Subtype C by Plasma Antibodies Targeting a Quaternary Epitope Including Residues in the V2 Loop

Journal of Virology (2011)

Penny L. Moore Elin S. Gray Daniel J. Sheward Maphuti Madiga Nthabeleng Ranchobe

ABSTRACT The targets of broadly cross-neutralizing (BCN) antibodies are of great interest in the HIV vaccine field. We have identified a subtype C HIV-1-superinfected individual, CAP256, with high-level BCN activity, and characterized the antibody specificity mediating breadth. CAP256 developed potent BCN activity peaking at 3 years postinfection, neutralizing 32 (76%) of 42 heterologous viruses, with titers of antibodies against some viruses exceeding 1:10,000. CAP256 showed a subtype bias, preferentially neutralizing subtype C and A viruses over subtype B viruses. CAP256 BCN serum targeted a quaternary epitope which included the V1V2 region. Further mapping identified residues F159, N160, L165, R166, D167, K169, and K171 (forming the FN/LRD-K-K motif) in the V2 region as crucial to the CAP256 epitope. However, the fine specificity of the BCN response varied over time and, while consistently dependent on R166 and K169, became gradually less dependent on D167 and K171, possibly contributing to the incremental increase in breadth over 4 years. The presence of an intact FN/LRD-K-K motif in heterologous viruses was associated with sensitivity, although the length of the adjacent V1 loop modulated the degree of sensitivity, with a shorter V1 region significantly associated with higher titers. Repair of the FN/LRD-K-K motif in resistant heterologous viruses conferred sensitivity, with titers sometimes exceeding 1:10,000. Comparison of the CAP256 epitope with that of the PG9/PG16 monoclonal antibodies suggested that these epitopes overlapped, adding to the mounting evidence that this may represent a common neutralization target that should be further investigated as a potential vaccine candidate.

Heterologous

V3 loop

Linear epitope

10.1128/jvi.02658-10

Cite

Citations (162)

The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256

PLoS ONE (2018)

Michiel T. van Diepen Rosamund Chapman Penny L. Moore Emmanuel Margolin Tandile Hermanus

With the HIV-1 epidemic in southern Africa still rising, a prophylactic vaccine against the region's most prolific subtype (subtype C) would be a significant step forward. In this paper we report on the effect of 2 different adjuvants, AddaVax and AlhydroGel, formulated with HIV-1 subtype C gp140, on the development of binding and neutralising antibody titres in rabbits. AddaVax is a squalene-based oil-in-water nano-emulsion (similar to MF59) which can enhance both cellular and humoral immune responses, whilst AlhydroGel (aluminium hydroxide gel) mainly drives a Th2 response. The gp140 gene tested was derived from the superinfecting virus (SU) from participant CAP256 in the CAPRISA 002 Acute infection cohort. The furin cleavage site of the Env protein was replaced with a flexible linker and an I559P mutation introduced. Lectin affinity purified soluble Env protein was mainly trimeric as judged by molecular weight using BN-PAGE and contained intact broadly neutralising epitopes for the V3-glycan supersite (monoclonal antibodies PGT128 and PGT135), the CD4 binding site (VRC01) and the V2-glycan (PG9) but not for the trimer-specific monoclonal antibodies PG16, PGT145 and CAP256-VRC26_08. When this soluble Env protein was tested in rabbits, AlhydroGel significantly enhanced soluble Env and V1V2 binding antibodies when compared to AddaVax. Finally, AlhydroGel resulted in significantly higher neutralization titres for a subtype C Tier 1A virus (MW965.26) and increased neutralization breadth to Tier 1A and 1B viruses. However, no autologous Tier 2 neutralisation was observed. These data suggest that adjuvant selection is critical for developing a successful vaccine and AlhydroGel should be further investigated. Additional purification of trimeric native-like CAP256 Env and/or priming with DNA or MVA might enhance the induction of neutralizing antibodies and possible Tier 2 HIV-1 neutralisation.

Furin

Polyclonal antibodies

10.1371/journal.pone.0208310

Cite

Citations (18)

Comparison of the neutralization sensitivity of South African and Indian HIV-1 subtype C viruses to South African plasma antibodies

Retrovirology (2012)

Tandile Hermanus Nonhlanhla N. Mkhize Patricia M. Moore Molati Nonyane J Battacharya

Methods Plasma from 44 chronically HIV-1 subtype C infected SA individuals in the CAPRISA 002 Acute Infection cohort were used to assess the neutralization sensitivity of 10 SA and 9 Indian Tier 2 viruses in a TZM-bl assay. Intra-subtype neutralization activity between SA and Indian viruses was determined. The envelope sequence of the Indian panel was analyzed in order to identify epitopes known to be targeted by the neutralizing antibodies in a subset of the CAPRISA plasmas.

10.1186/1742-4690-9-s2-p66

Cite

Citations (1)

Fc effector activity and neutralization against SARS-CoV-2 BA.4 is compromised in convalescent sera, regardless of the infecting variant

bioRxiv (Cold Spring Harbor Laboratory) (2022)

Simone I. Richardson Prudence Kgagudi Nelia P. Manamela Haajira Kaldine Elizabeth M. Venter

Summary The SARS-CoV-2 Omicron BA.1 variant, which exhibits high level neutralization resistance, has since evolved into several sub-lineages including BA.4 and BA.5, which have dominated the fifth wave of infection in South Africa. Here we assessed the sensitivity of BA.4 to neutralization and antibody dependent cellular cytotoxicity (ADCC) in convalescent donors infected with four previous variants of SARS-CoV-2, as well as in post-vaccination breakthrough infections (BTIs) caused by Delta or BA.1. We confirm that BA.4 shows high level resistance to neutralization, regardless of the infecting variant. However, breakthrough infections, which trigger potent neutralization, retained activity against BA.4, albeit at reduced titers. Fold reduction of neutralization in BTIs was lower than that seen in unvaccinated convalescent donors, suggesting maturation of neutralizing responses to become more resilient against VOCs in hybrid immunity. BA.4 sensitivity to ADCC was reduced but remained detectable in both convalescent donors and in BTIs. Overall, the high neutralization resistance of BA.4, even to antibodies from BA.1 infections, provides an immunological mechanism for the rapid spread of BA.4 immediately after a BA.1-dominated wave. Furthermore, although ADCC activity against BA.4 was reduced, residual activity may nonetheless contribute to the protection from disease.

10.1101/2022.07.14.500042

Cite

Citations (3)

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants

PLOS Global Public Health (2024)

Catherine Riou Jinal N. Bhiman Yashica Ganga Shobna Sawry Frances Ayres

We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Overall, in the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: The study has been registered to the South African National Clinical Trial Registry (SANCTR): DOH-27-012022-7841 . The approval letter from SANCTR has been provided in the up-loaded documents.

10.1371/journal.pgph.0002703

Cite

Citations (3)

Antibody-dependent cellular cytotoxicity against SARS-CoV-2 Omicron sub-lineages is reduced in convalescent sera regardless of infecting variant

Cell Reports Medicine (2022)

Simone I. Richardson Prudence Kgagudi Nelia P. Manamela Haajira Kaldine Elizabeth M. Venter

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.4 and BA.5 variants caused major waves of infections. Here, we assess the sensitivity of BA.4 to binding, neutralization, and antibody-dependent cellular cytotoxicity (ADCC) potential, measured by FcγRIIIa signaling, in convalescent donors infected with four previous variants of SARS-CoV-2, as well as in post-vaccination breakthrough infections (BTIs) caused by Delta or BA.1. We confirm that BA.4 shows high-level neutralization resistance regardless of the infecting variant. However, BTIs retain activity against BA.4, albeit at reduced titers. BA.4 sensitivity to ADCC is reduced compared with other variants but with smaller fold losses compared with neutralization and similar patterns of cross-reactivity. Overall, the high neutralization resistance of BA.4, even to antibodies from BA.1 infection, provides an immunological mechanism for the rapid spread of BA.4 immediately after a BA.1-dominated wave. Furthermore, although ADCC potential against BA.4 is reduced, residual activity may contribute to observed protection from severe disease.

10.1016/j.xcrm.2022.100910

Cite

Citations (14)