Panels of HIV-1 Subtype C Env Reference Strains for Standardized Neutralization Assessments

Journal of Virology - Tập 91 Số 19 - 2017
Peter Hraber1, Cecilia Rademeyer2, Carolyn Williamson2, Michael S. Seaman3, Raphaël Gottardo4, Haili Tang5, Kelli Greene5, Hongmei Gao5, Celia C. LaBranche5, John R. Mascola6, Lynn Morris7, David C. Montefiori5, Bette Korber8,1
1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, New Mexico, USA
2Division of Medical Virology & Institute of Infectious Diseases and Molecular Medicine, University of Cape Town and NHLS, Cape Town, South Africa
3Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
4Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
5Department of Surgery, Duke University Medical Center, Durham, North Carolina. USA
6Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
7National Institute for Communicable Diseases, Johannesburg, South Africa
8New Mexico Consortium, Los Alamos, New Mexico, USA

Tóm tắt

ABSTRACTIn the search for effective immunologic interventions to prevent and treat HIV-1 infection, standardized reference reagents are a cost-effective way to maintain robustness and reproducibility among immunological assays. To support planned and ongoing studies where clade C predominates, here we describe three virus panels, chosen from 200 well-characterized clade C envelope (Env)-pseudotyped viruses from early infection. All 200 Envs were expressed as a single round of replication pseudoviruses and were tested to quantify neutralization titers by 16 broadly neutralizing antibodies (bnAbs) and sera from 30 subjects with chronic clade C infections. We selected large panels of 50 and 100 Envs either to characterize cross-reactive breadth for sera identified as having potent neutralization activity based on initial screening or to evaluate neutralization magnitude-breadth distributions of newly isolated antibodies. We identified these panels by downselection after hierarchical clustering of bnAb neutralization titers. The resulting panels represent the diversity of neutralization profiles throughout the range of virus sensitivities identified in the original panel of 200 viruses. A small 12-Env panel was chosen to screen sera from vaccine trials or natural-infection studies for neutralization responses. We considered panels selected by previously described methods but favored a computationally informed method that enabled selection of viruses representing diverse neutralization sensitivity patterns, given that we do nota prioriknow what the neutralization-response profile of vaccine sera will be relative to that of sera from infected individuals. The resulting 12-Env panel complements existing panels. Use of standardized panels enables direct comparisons of data from different trials and study sites testing HIV-1 clade C-specific products.IMPORTANCEHIV-1 group M includes nine clades and many recombinants. Clade C is the most common lineage, responsible for roughly half of current HIV-1 infections, and is a focus for vaccine design and testing. Standard reference reagents, particularly virus panels to study neutralization by antibodies, are crucial for developing cost-effective and yet rigorous and reproducible assays against diverse examples of this variable virus. We developed clade C-specific panels for use as standardized reagents to monitor complex polyclonal sera for neutralization activity and to characterize the potency and breadth of cross-reactive neutralization by monoclonal antibodies, whether engineered or isolated from infected individuals. We chose from 200 southern African, clade C envelope-pseudotyped viruses with neutralization titers against 16 broadly neutralizing antibodies and 30 sera from chronic clade C infections. We selected panels to represent the diversity of bnAb neutralization profiles and Env neutralization sensitivities. Use of standard virus panels can facilitate comparison of results across studies and sites.

Từ khóa


Tài liệu tham khảo

10.1128/JVI.79.16.10103-10107.2005

10.1097/QAD.0b013e328342ff93

10.1128/JVI.00114-09

10.1086/431514

10.1097/01.aids.0000171418.91786.ad

10.1097/QAD.0b013e32832a1806

10.1016/j.virol.2008.12.025

10.1128/JVI.02051-08

10.1371/journal.ppat.1005742

10.1080/14712598.2017.1282457

10.3390/vaccines4020017

10.1128/JVI.02853-13

10.1086/654816

10.1093/infdis/jis367

10.1080/01621459.1963.10500845

Sneath PHA Sokal RR . 1973. Numerical taxonomy: the principles and practice of numerical classification. Freeman, San Francisco, CA.

10.1097/QAD.0000000000000106

10.1128/JVI.01730-06

10.1080/10635150390235520

10.1093/sysbio/syq010

10.1093/nar/gkv404

10.1128/JVI.00198-11

10.1128/JVI.01705-14

10.1128/JVI.02108-09

10.1371/journal.ppat.1006148

10.1002/0471142735.im1211s64

10.1016/j.jim.2013.11.022

10.1126/science.1187659

10.1126/science.1207532

10.1016/j.cell.2015.03.004

10.1128/JVI.02213-14

10.1016/j.cell.2015.05.007

10.1126/science.1207227

10.1038/nature10373

10.1073/pnas.1217207109

10.1038/nature13036

10.1128/JVI.01791-15

10.1126/science.1178746

10.1073/pnas.1415789111

10.1038/nature11544

10.1128/JVI.75.22.10892-10905.2001

10.1007/0-306-47815-3_5

10.1371/journal.pcbi.1004185

Tibshirani R . 1996. Regression shrinkage and selection via the lasso. J R Stat Soc Series B Stat Methodol58:267–288.

Friedman J Hastie T Tibshirani R . 2008. Regularization paths for generalized linear models via coordinate descent. J Stat Softw33:1–22.

Thông tin
Thông tin xuất bản

Journal of Virology

Tập 91 Số 19

Thông tin tác giả