15 results on '"Bhiman J"'
Search Results
2. A1 The role of virus-antibody co-evolution in the development of a V3-glycan-directed HIV-1 broadly neutralizing antibody lineage
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Kitchin, D, primary, Bhiman, J, additional, Mvududu, D, additional, Oosthuysen, B, additional, Lambson, B, additional, Madzorera, S, additional, Anthony, C, additional, Abdool Karim, S S, additional, Garrett, N J, additional, Doria-Rose, N A, additional, Mascola, J R, additional, Morris, L, additional, and Moore, P L, additional
- Published
- 2019
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3. A38 Diversity analyses of HIV-1 envelope glycoproteins in HIV-infected individuals with and without broadly neutralizing antibodies
- Author
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Mabvakure, B., primary, Scheepers, C., additional, Nonyane, M., additional, Lambson, B., additional, Madzorera, S., additional, Kitchin, D., additional, Bhiman, J., additional, Wibmer, K., additional, Abdool Karim, S., additional, Williamson, C., additional, Morris, L., additional, and Moore, P.L., additional
- Published
- 2017
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4. Efficacy of the ChAdOxl nCoV-19 Covid-19 Vaccine against the B.1.351 Variant.
- Author
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Madhi, S. A., Baillie, V., Cutland, C. L., Voysey, M., Koen, A. L., Fairlie, L., Padayachee, S. D., Dheda, K., Barnabas, S. L., Bhorat, Q. E., Briner, C., Kwatra, G., Ahmed, K., Aley, P., Bhikha, S., Bhiman, J. N., Bhorat, A.'.E., Plessis, J. du, Esmail, A., and Groenewald, M.
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COVID-19 vaccines , *VACCINE effectiveness , *SARS-CoV-2 , *HIV , *COVID-19 - Abstract
BACKGROUND: Assessment of the safety and efficacy of vaccines against the severe acute respiradetory syndrome coronavirus 2 (SARS-CoV-2) in different populations is essential, as is investigation of the efficacy of the vaccines against emerging SARS-CoV-2 variants concern, including the B.1.351 (501Y.V2) variant first identified in South Africa. METHODS: We conducted a multicenter, double-blind, randomized, controlled trial to assess the safety and efficacy of the ChAdOxl nCoV-19 vaccine (AZD1222) in people not infected with the human immunodeficiency virus (HIV) in South Africa. Participants 18 to less than 65 years of age were assigned in a 1:1 ratio to receive two doses of vaccine containing 5x1O10 viral particles or placebo (0.9% sodium chloride solution) 21 to 35 days apart. Serum samples obtained from 25 participants after the second dose were tested by pseudovirus and live-virus neutralization assays against the original D6146 virus and the B.1.351 variant. The primary end points were safety and efficacy of the vaccine against laboratory-confirmed symptomatic coronavirus 2019 illness (Covid-19) more than 14 days after the second dose. RESULTS: Between June 24 and November 9,2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid49 developed in 23 of 717 placebo recipients (3.296) and in 19 of750 vaccine recipients (2.596), for an efficacy of 21.9% (95% confidence interval ICI], -49.9 to 59.8). Among the 42 participants with Covid49, 39 cases (95.1% of 41 with sequencing data) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, 76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups. CONCLUSIONS: A two-dose regimen of the ChAdOxl nCoV-19 vaccine did not show protection against mild-to-moderate Covid49 due to the B.1.351 variant. [ABSTRACT FROM AUTHOR]
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- 2021
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5. Priming antibody responses to the fusion peptide in rhesus macaques.
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Cottrell CA, Pratap PP, Cirelli KM, Carnathan DG, Enemuo CA, Antanasijevic A, Ozorowski G, Sewall LM, Gao H, Allen JD, Nogal B, Silva M, Bhiman J, Pauthner M, Irvine DJ, Montefiori D, Crispin M, Burton DR, Silvestri G, Crotty S, and Ward AB
- Abstract
Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to prime and elicit antibody responses against the conserved fusion peptide (FP). GC responses and antibody specificities were tracked longitudinally using lymph node fine-needle aspirates and electron microscopy polyclonal epitope mapping (EMPEM), respectively, to show antibody responses to the FP/N611 glycan hole region were primed, although exhibited limited neutralization breadth. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design., (© 2024. The Author(s).)
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- 2024
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6. Knowledge, attitudes, practices and intention to get vaccinated against COVID-19: results from a cross-sectional survey in three peri-urban communities in South Africa.
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Weiner R, Magni S, Maakamadi T, Fellows T, Aitken S, Yun J, Tempia S, von Gottberg A, Bhiman J, Walaza S, Moyes J, Cawood C, Martinson N, Lebina L, Cohen C, and Wolter N
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- Humans, Aged, Cross-Sectional Studies, South Africa epidemiology, Health Knowledge, Attitudes, Practice, Seroepidemiologic Studies, Intention, COVID-19 prevention & control
- Abstract
Introduction: South Africa has the largest number of confirmed cases of COVID-19 in Africa. Data to inform public health strategies to mitigate the spread of new variants and severity of disease is needed, including information on knowledge, attitudes and practices (KAP) regarding COVID-19, factors associated with intention to get vaccinated, and viewpoints on reliable sources of data., Methods: we investigated these topics as part of the COVID-19 healthcare utilization and seroprevalence (HUTS) cross-sectional survey in three communities in South Africa: Mitchell´s Plain (Western Cape Province), Pietermaritzburg (KwaZulu-Natal Province) and Klerksdorp (North West Province) during and after the second wave of COVID-19 prior to vaccine availability., Results: primary caregivers from 5799 households participated in the study, 41.1% from Pietermaritzburg, 34.2% from Klerksdorp and 24.7% from Mitchells Plain. Two-thirds and 94.7% of respondents had correct knowledge on the cause and spread of COVID-19, respectively. Knowledge measures were significantly associated with age less than 65 years, the highest level of education and site (Mitchells Plain). Desired preventive behaviors were associated with higher socio-economic status. While 64.7% of people intended to get vaccinated, those over 64 years of age were more likely to intend to vaccinate (aOR: 1.25, 95% CI: 1.06-1.47). Vaccine intention related to protection of self (58.4%) and family (40.0%). The most trusted source of COVID-19 information was television (59.3%) followed by radio (20.0%)., Conclusion: these data can be used to design targeted public health campaigns for the current COVID-19 and future epidemics, ensuring that socio-economic constraints and preference for trusted information are considered., Competing Interests: The authors declare no competing interest., (Copyright: Renay Weiner et al.)
- Published
- 2023
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7. Focusing antibody responses to the fusion peptide in rhesus macaques.
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Cottrell CA, Pratap PP, Cirelli KM, Carnathan DG, Enemuo CA, Antanasijevic A, Ozorowski G, Sewall LM, Gao H, Greene KM, Allen JD, Ngo JT, Choe Y, Nogal B, Silva M, Bhiman J, Pauthner M, Irvine DJ, Montefiori D, Crispin M, Burton DR, Silvestri G, Crotty S, and Ward AB
- Abstract
Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to elicit immune responses against the conserved fusion peptide. Antibody specificities and GC responses were tracked longitudinally using electron microscopy polyclonal epitope mapping (EMPEM) and lymph node fine-needle aspirates, respectively. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design., Competing Interests: Conflicts of Interest None.
- Published
- 2023
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8. Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020.
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Williams T, Jackson S, Barr I, Bi S, Bhiman J, Ellis J, von Gottberg A, Lindstrom S, Peret T, Rughooputh S, Viegas M, Hirve S, Zambon M, Zhang W, Dia N, Razanazatovo N, Al-Nabet ADMH, Abubakar A, Tivane A, Barakat A, Naguib A, Aziz A, Vicari A, Moen A, Govindakarnavar A, Hall A, Darmaa B, Nathalie B, Herring B, Caetano BC, Whittaker B, Baumeister E, Nakouné E, Guthrie E, Inbanathan F, Nair H, Campbell H, Kadjo HA, Oumzil H, Heraud JM, Mott JA, Namulondo J, Leite J, Nahapetyan K, Al Ariqi L, Gazo MHI, Chadha M, Pisareva M, Venter M, Siqueira MM, Lumandas M, Niang M, Albuaini M, Salman M, Oberste S, Srikantiah P, Tang P, Couto P, Smith P, Coyle PV, Dussart P, Nguyen PN, Okada PA, Wijesinghe PR, Samuel R, Brown R, Pebody R, Fasce R, Jha R, Lindstrom S, Gerber S, Potdar V, Dong X, and Deng YM
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- United States, Humans, Laboratories, World Health Organization, Australia, Respiratory Syncytial Virus, Human genetics, Viruses
- Abstract
Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019-2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019-2020 WHO RSV EQA., Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories., Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping., Conclusions: The WHO RSV EQA 2019-2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets., Competing Interests: No conflict of interest is declared by authors., (© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)
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- 2023
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9. High prevalence of SARS-CoV-2 antibodies in pregnant women after the second wave of infections in the inner-city of Johannesburg, Gauteng Province, South Africa.
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Sawry S, Le Roux J, Wolter N, Mbatha P, Bhiman J, Balkus J, von Gottberg A, Cohen C, Chersich M, Kekana M, Ndlovu T, Shipalana A, Mthimunye W, Patel F, Gous H, Walaza S, Tempia S, Rees H, and Fairlie L
- Subjects
- Pregnancy, Female, Humans, Adult, Prevalence, Pregnant Women, Seroepidemiologic Studies, South Africa epidemiology, Cross-Sectional Studies, SARS-CoV-2, Antibodies, Viral, COVID-19 epidemiology, HIV Infections epidemiology
- Abstract
Objectives: After South Africa's second wave of COVID-19, this study estimated the SARS-CoV-2 seroprevalence among pregnant women in inner-city Johannesburg, South Africa., Methods: In this cross-sectional survey, 500 pregnant women who were non-COVID-19-vaccinated (aged ≥12 years) were enrolled, and demographic and clinical data were collected. Serum samples were tested using the Wantai SARS-CoV-2 spike antibody enzyme-linked immunosorbent assay and Roche Elecsys® anti-SARS-CoV-2 nucleocapsid antibody assays. Seropositivity was defined as SARS-CoV-2 antibodies on either (primary) or both (secondary) assays. Univariate Poisson regression assessed risk factors associated with seropositivity., Results: The median age was 27.4 years, and HIV prevalence was 26.7%. SARS-CoV-2 seroprevalence was 64.0% (95% confidence interval [CI]: 59.6-68.2%) on the primary and 54% (95% CI: 49.5-58.4%) on the secondary measure. Most (96.6%) women who were SARS-CoV-2-seropositive reported no symptoms. On the Roche assay, we detected lower seroprevalence among women living with HIV than women without HIV (48.9% vs 61.7%, P-value = 0.018), and especially low levels among women living with HIV with a clusters of differentiation 4 <350 cells/ml compared with women without immune suppression (22.2% vs 56.4%, prevalence rate ratio = 0.4; 95% CI: 0.2-0.9; P-value = 0.046)., Conclusion: Pregnant women attending routine antenatal care had a high SARS-CoV-2 seroprevalence after the second wave in South Africa, and most had asymptomatic infections. Seroprevalence surveys in pregnant women present a feasible method of monitoring the course of the pandemic over time., Competing Interests: Declaration of competing interest CC has received grant support from Sanofi Pasteur and Advanced Vaccine Initiative and payment of travel costs from Parexel. NW and AvG have received grant support from Sanofi Pasteur and the Bill and Melinda Gates Foundation., (Copyright © 2022. Published by Elsevier Ltd.)
- Published
- 2022
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10. Reduced amplification efficiency of the RNA-dependent-RNA-polymerase target enables tracking of the Delta SARS-CoV-2 variant using routine diagnostic tests.
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Valley-Omar Z, Marais G, Iranzadeh A, Naidoo M, Korsman S, Maponga T, Hussey H, Davies MA, Boulle A, Doolabh D, Laubscher M, Wojno J, Deetlefs JD, Maritz J, Scott L, Msomi N, Naicker C, Tegally H, de Oliveira T, Bhiman J, Williamson C, Preiser W, Hardie D, and Hsiao NY
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- Diagnostic Tests, Routine, Humans, RNA, RNA-Dependent RNA Polymerase, COVID-19 diagnosis, COVID-19 virology, COVID-19 Nucleic Acid Testing, SARS-CoV-2 genetics
- Abstract
Routine SARS-CoV-2 surveillance in the Western Cape region of South Africa (January-August 2021) found a reduced RT-PCR amplification efficiency of the RdRp-gene target of the Seegene, Allplex 2019-nCoV diagnostic assay from June 2021 when detecting the Delta variant. We investigated whether the reduced amplification efficiency denoted by an increased RT-PCR cycle threshold value (RΔE) can be used as an indirect measure of SARS-CoV-2 Delta variant prevalence. We found a significant increase in the median RΔE for patient samples tested from June 2021, which coincided with the emergence of the SARS-CoV-2 Delta variant within our sample set. Whole genome sequencing on a subset of patient samples identified a highly conserved G15451A, non-synonymous mutation exclusively within the RdRp gene of Delta variants, which may cause reduced RT-PCR amplification efficiency. While whole genome sequencing plays an important in identifying novel SARS-CoV-2 variants, monitoring RΔE value can serve as a useful surrogate for rapid tracking of Delta variant prevalence., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2022
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11. Rapid epidemic expansion of the SARS-CoV-2 Omicron variant in southern Africa.
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Viana R, Moyo S, Amoako DG, Tegally H, Scheepers C, Althaus CL, Anyaneji UJ, Bester PA, Boni MF, Chand M, Choga WT, Colquhoun R, Davids M, Deforche K, Doolabh D, du Plessis L, Engelbrecht S, Everatt J, Giandhari J, Giovanetti M, Hardie D, Hill V, Hsiao NY, Iranzadeh A, Ismail A, Joseph C, Joseph R, Koopile L, Kosakovsky Pond SL, Kraemer MUG, Kuate-Lere L, Laguda-Akingba O, Lesetedi-Mafoko O, Lessells RJ, Lockman S, Lucaci AG, Maharaj A, Mahlangu B, Maponga T, Mahlakwane K, Makatini Z, Marais G, Maruapula D, Masupu K, Matshaba M, Mayaphi S, Mbhele N, Mbulawa MB, Mendes A, Mlisana K, Mnguni A, Mohale T, Moir M, Moruisi K, Mosepele M, Motsatsi G, Motswaledi MS, Mphoyakgosi T, Msomi N, Mwangi PN, Naidoo Y, Ntuli N, Nyaga M, Olubayo L, Pillay S, Radibe B, Ramphal Y, Ramphal U, San JE, Scott L, Shapiro R, Singh L, Smith-Lawrence P, Stevens W, Strydom A, Subramoney K, Tebeila N, Tshiabuila D, Tsui J, van Wyk S, Weaver S, Wibmer CK, Wilkinson E, Wolter N, Zarebski AE, Zuze B, Goedhals D, Preiser W, Treurnicht F, Venter M, Williamson C, Pybus OG, Bhiman J, Glass A, Martin DP, Rambaut A, Gaseitsiwe S, von Gottberg A, and de Oliveira T
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- Antibodies, Neutralizing immunology, Botswana epidemiology, COVID-19 immunology, COVID-19 transmission, Humans, Models, Molecular, Mutation, Phylogeny, Recombination, Genetic, SARS-CoV-2 classification, SARS-CoV-2 immunology, South Africa epidemiology, Spike Glycoprotein, Coronavirus genetics, Spike Glycoprotein, Coronavirus immunology, COVID-19 epidemiology, COVID-19 virology, Immune Evasion, SARS-CoV-2 isolation & purification
- Abstract
The SARS-CoV-2 epidemic in southern Africa has been characterized by three distinct waves. The first was associated with a mix of SARS-CoV-2 lineages, while the second and third waves were driven by the Beta (B.1.351) and Delta (B.1.617.2) variants, respectively
1-3 . In November 2021, genomic surveillance teams in South Africa and Botswana detected a new SARS-CoV-2 variant associated with a rapid resurgence of infections in Gauteng province, South Africa. Within three days of the first genome being uploaded, it was designated a variant of concern (Omicron, B.1.1.529) by the World Health Organization and, within three weeks, had been identified in 87 countries. The Omicron variant is exceptional for carrying over 30 mutations in the spike glycoprotein, which are predicted to influence antibody neutralization and spike function4 . Here we describe the genomic profile and early transmission dynamics of Omicron, highlighting the rapid spread in regions with high levels of population immunity., (© 2022. The Author(s).)- Published
- 2022
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12. SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection.
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Cele S, Jackson L, Khoury DS, Khan K, Moyo-Gwete T, Tegally H, San JE, Cromer D, Scheepers C, Amoako D, Karim F, Bernstein M, Lustig G, Archary D, Smith M, Ganga Y, Jule Z, Reedoy K, Hwa SH, Giandhari J, Blackburn JM, Gosnell BI, Abdool Karim SS, Hanekom W, von Gottberg A, Bhiman J, Lessells RJ, Moosa MS, Davenport MP, de Oliveira T, Moore PL, and Sigal A
- Abstract
The emergence of SARS-CoV-2 Omicron, first identified in Botswana and South Africa, may compromise vaccine effectiveness and the ability of antibodies triggered by previous infection to protect against re-infection (1). Here we investigated whether Omicron escapes antibody neutralization in South Africans, either previously SARS-CoV-2 infected or uninfected, who were vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa and compared plasma neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation, observing that Omicron still required ACE2 to infect. For neutralization, blood samples were taken soon after vaccination, so that vaccine elicited neutralization was close to peak. Neutralization capacity of the D614G virus was much higher in infected and vaccinated versus vaccinated only participants but both groups had 22-fold Omicron escape from vaccine elicited neutralization. Previously infected and vaccinated individuals had residual neutralization predicted to confer 73% protection from symptomatic Omicron infection, while those without previous infection were predicted to retain only about 35%. Both groups were predicted to have substantial protection from severe disease. These data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly boosting, could maintain reasonable effectiveness against Omicron. A waning neutralization response is likely to decrease vaccine effectiveness below these estimates. However, since protection from severe disease requires lower neutralization levels and involves T cell immunity, such protection may be maintained.
- Published
- 2021
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13. A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity.
- Author
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Silva M, Kato Y, Melo MB, Phung I, Freeman BL, Li Z, Roh K, Van Wijnbergen JW, Watkins H, Enemuo CA, Hartwell BL, Chang JYH, Xiao S, Rodrigues KA, Cirelli KM, Li N, Haupt S, Aung A, Cossette B, Abraham W, Kataria S, Bastidas R, Bhiman J, Linde C, Bloom NI, Groschel B, Georgeson E, Phelps N, Thomas A, Bals J, Carnathan DG, Lingwood D, Burton DR, Alter G, Padera TP, Belcher AM, Schief WR, Silvestri G, Ruprecht RM, Crotty S, and Irvine DJ
- Subjects
- Animals, B-Lymphocytes immunology, CD4-Positive T-Lymphocytes immunology, Female, Lymph physiology, Macaca mulatta, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Nanoparticles, Rats, Rats, Wistar, Adaptive Immunity drug effects, Adjuvants, Immunologic pharmacology, Lymph drug effects, Saponins pharmacology, Toll-Like Receptors agonists
- Abstract
Saponins are potent and safe vaccine adjuvants, but their mechanisms of action remain incompletely understood. Here, we explored the properties of several saponin formulations, including immune-stimulatory complexes (ISCOMs) formed by the self-assembly of saponin and phospholipids in the absence or presence of the Toll-like receptor 4 agonist monophosphoryl lipid A (MPLA). We found that MPLA self-assembles with saponins to form particles physically resembling ISCOMs, which we termed saponin/MPLA nanoparticles (SMNP). Saponin-containing adjuvants exhibited distinctive mechanisms of action, altering lymph flow in a mast cell–dependent manner and promoting antigen entry into draining lymph nodes. SMNP was particularly effective, exhibiting even greater potency than the compositionally related adjuvant AS01
B in mice, and primed robust germinal center B cell, TFH , and HIV tier 2 neutralizing antibodies in nonhuman primates. Together, these findings shed new light on mechanisms by which saponin adjuvants act to promote the immune response and suggest that SMNP may be a promising adjuvant in the setting of HIV, SARS-CoV-2, and other pathogens.- Published
- 2021
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14. Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.
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Antanasijevic A, Sewall LM, Cottrell CA, Carnathan DG, Jimenez LE, Ngo JT, Silverman JB, Groschel B, Georgeson E, Bhiman J, Bastidas R, LaBranche C, Allen JD, Copps J, Perrett HR, Rantalainen K, Cannac F, Yang YR, de la Peña AT, Rocha RF, Berndsen ZT, Baker D, King NP, Sanders RW, Moore JP, Crotty S, Crispin M, Montefiori DC, Burton DR, Schief WR, Silvestri G, and Ward AB
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- Animals, Antibodies, Monoclonal chemistry, Antibodies, Monoclonal ultrastructure, Antibodies, Neutralizing chemistry, Antibodies, Neutralizing ultrastructure, Cryoelectron Microscopy methods, Epitopes chemistry, Epitopes immunology, Epitopes metabolism, Glycosylation, HIV Antibodies chemistry, HIV Antibodies ultrastructure, HIV Infections immunology, HIV Infections prevention & control, HIV Infections virology, HIV-1 genetics, HIV-1 immunology, HIV-1 metabolism, Humans, Macaca mulatta, Models, Molecular, Protein Conformation, env Gene Products, Human Immunodeficiency Virus ultrastructure, AIDS Vaccines immunology, Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, Antibody Formation immunology, HIV Antibodies immunology, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
Engineered ectodomain trimer immunogens based on BG505 envelope glycoprotein are widely utilized as components of HIV vaccine development platforms. In this study, we used rhesus macaques to evaluate the immunogenicity of several stabilized BG505 SOSIP constructs both as free trimers and presented on a nanoparticle. We applied a cryoEM-based method for high-resolution mapping of polyclonal antibody responses elicited in immunized animals (cryoEMPEM). Mutational analysis coupled with neutralization assays were used to probe the neutralization potential at each epitope. We demonstrate that cryoEMPEM data can be used for rapid, high-resolution analysis of polyclonal antibody responses without the need for monoclonal antibody isolation. This approach allowed to resolve structurally distinct classes of antibodies that bind overlapping sites. In addition to comprehensive mapping of commonly targeted neutralizing and non-neutralizing epitopes in BG505 SOSIP immunogens, our analysis revealed that epitopes comprising engineered stabilizing mutations and of partially occupied glycosylation sites can be immunogenic., (© 2021. The Author(s).)
- Published
- 2021
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15. Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.
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Bradley T, Fera D, Bhiman J, Eslamizar L, Lu X, Anasti K, Zhang R, Sutherland LL, Scearce RM, Bowman CM, Stolarchuk C, Lloyd KE, Parks R, Eaton A, Foulger A, Nie X, Karim SSA, Barnett S, Kelsoe G, Kepler TB, Alam SM, Montefiori DC, Moody MA, Liao HX, Morris L, Santra S, Harrison SC, and Haynes BF
- Subjects
- Amino Acid Sequence, Animals, Female, Humans, Macaca mulatta, Male, Molecular Sequence Data, AIDS Vaccines immunology, AIDS Vaccines pharmacology, Antibodies, Neutralizing immunology, HIV Antibodies immunology, HIV-1 genetics, HIV-1 immunology, env Gene Products, Human Immunodeficiency Virus genetics, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
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