Generation and Characterization of a Bivalent HIV-1 Subtype C gp120 Protein Boost for Proof-of-Concept HIV Vaccine Efficacy Trials in Southern Africa
| Autor: | Celia C. LaBranche, Mark Wininger, Andrea Carfi, Barton F. Haynes, Carlo Zambonelli, David C. Montefiori, Heather Desaire, Hua-Xin Liao, Daniel F. Clark, Samuel Stephenson, Eden P. Go, Susan W. Barnett, Susan Hilt, Antu K. Dey, Ronald Swanstrom |
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| Rok vydání: | 2016 |
| Předmět: |
RNA viruses
0301 basic medicine Glycosylation Physiology HIV Antigens Glycobiology lcsh:Medicine HIV Infections HIV Envelope Protein gp120 Pathology and Laboratory Medicine Biochemistry Epitope Epitopes 0302 clinical medicine Immunodeficiency Viruses Immune Physiology Cricetinae HIV Seropositivity Medicine and Health Sciences Disulfides 030212 general & internal medicine Post-Translational Modification HIV vaccine lcsh:Science Mammals AIDS Vaccines chemistry.chemical_classification Vaccines Clinical Trials as Topic Immune System Proteins Multidisciplinary Organic Compounds Physics Chinese hamster ovary cell Antibodies Monoclonal virus diseases Animal Models 3. Good health Physical sciences Chemistry Treatment Outcome Medical Microbiology Viral Pathogens Viruses Vertebrates Vaccination and immunization Female Rabbits Pathogens Antibody Research Article Antigenicity Chemical physics Immunology Carbohydrates CHO Cells Biology Research and Analysis Methods Microbiology Antibodies Africa Southern 03 medical and health sciences Model Organisms Cricetulus Viral envelope Virology Retroviruses Animals Humans Antigens Microbial Pathogens Preventive medicine Viral vaccines Immune Sera lcsh:R Lentivirus Organic Chemistry Organisms Chemical Compounds HIV vaccines Biology and Life Sciences HIV Proteins Dimers (Chemical physics) Molecular biology Public and occupational health 030104 developmental biology chemistry Amniotes HIV-1 biology.protein lcsh:Q Protein Multimerization Glycoprotein Mannose |
| Zdroj: | PLoS ONE PLoS ONE, Vol 11, Iss 7, p e0157391 (2016) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0157391 |
| Popis: | The viral envelope glycoprotein (Env) is the major target for antibody (Ab)-mediated vaccine development against the Human Immunodeficiency Virus type 1 (HIV-1). Although several recombinant Env antigens have been evaluated in clinical trials, only the surface glycoprotein, gp120, (from HIV-1 subtype B, MN, and subtype CRF_01AE, A244) used in the ALVAC prime-AIDSVAX gp120 boost RV144 Phase III HIV vaccine trial was shown to contribute to protective efficacy, although modest and short-lived. Hence, for clinical trials in southern Africa, a bivalent protein boost of HIV-1 subtype C gp120 antigens composed of two complementary gp120s, from the TV1.C (chronic) and 1086.C (transmitted founder) HIV-1 strains, was selected. Stable Chinese Hamster Cell (CHO) cell lines expressing these gp120s were generated, scalable purification methods were developed, and a detailed analytical analysis of the purified proteins was conducted that showed differences and complementarity in the antigenicity, glycan occupancy, and glycan content of the two gp120 molecules. Moreover, mass spectrometry revealed some disulfide heterogeneity in the expressed proteins, particularly in V1V2-C1 region and most prominently in the TV1 gp120 dimers. These dimers not only lacked binding to certain key CD4 binding site (CD4bs) and V1V2 epitope-directed ligands but also elicited reduced Ab responses directed to those epitopes, in contrast to monomeric gp120, following immunization of rabbits. Both monomeric and dimeric gp120s elicited similarly high titer Tier 1 neutralizing Abs as measured in standard virus neutralization assays. These results provide support for clinical evaluations of bivalent preparations of purified monomeric TV1.C and 1086.C gp120 proteins. |
| Databáze: | OpenAIRE |
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