Aggregate complexes of HIV-1 induced by multimeric antibodies.

Stieh, Daniel J

King, Deborah F

Klein, Katja

Liu, Pinghuang

Shen, Xiaoying

Hwang, Kwan Ki

Ferrari, Guido

Montefiori, David C

Haynes, Barton

Pitisuttithum, Punnee

Kaewkungwal, Jaranit

Nitayaphan, Sorachai

Rerks-Ngarm, Supachai

Michael, Nelson L

Robb, Merlin L

Kim, Jerome H

Denny, Thomas N

Tomaras, Georgia D

Shattock, Robin J

England

2017-06-01T19:10:31Z

2017-06-01T19:10:31Z

2014-10-02

BACKGROUND: Antibody mediated viral aggregation may impede viral transfer across mucosal surfaces by hindering viral movement in mucus, preventing transcytosis, or reducing inter-cellular penetration of epithelia thereby limiting access to susceptible mucosal CD4 T cells and dendritic cells. These functions may work together to provide effective immune exclusion of virus from mucosal tissue; however little is known about the antibody characteristics required to induce HIV aggregation. Such knowledge may be critical to the design of successful immunization strategies to facilitate viral immune exclusion at the mucosal portals of entry. RESULTS: The potential of neutralizing and non-neutralizing IgG and IgA monoclonals (mAbs) to induce HIV-1 aggregation was assessed by Dynamic light scattering (DLS). Although neutralizing and non-neutralizing IgG mAbs and polyclonal HIV-Ig efficiently aggregated soluble Env trimers, they were not capable of forming viral aggregates. In contrast, dimeric (but not monomeric) IgA mAbs induced stable viral aggregate populations that could be separated from uncomplexed virions. Epitope specificity influenced both the degree of aggregation and formation of higher order complexes by dIgA. IgA purified from serum of uninfected RV144 vaccine trial responders were able to efficiently opsonize viral particles in the absence of significant aggregation, reflective of monomeric IgA. CONCLUSIONS: These results collectively demonstrate that dIgA is capable of forming stable viral aggregates providing a plausible basis for testing the effectiveness of aggregation as a potential protection mechanism at the mucosal portals of viral entry.

https://www.ncbi.nlm.nih.gov/pubmed/25274446

s12977-014-0078-8

1742-4690

https://hdl.handle.net/10161/14673

eng

Springer Nature

Retrovirology

10.1186/s12977-014-0078-8

Antibodies, Monoclonal

HIV Antibodies

HIV-1

Humans

Immunoglobulin A

Immunoglobulin G

Aggregate complexes of HIV-1 induced by multimeric antibodies.

Journal article

Shen, Xiaoying|0000-0001-8076-1931|0000-0002-8387-3952

Ferrari, Guido|0000-0001-7747-3349

Montefiori, David C|0000-0003-0856-6319

Tomaras, Georgia D|0000-0001-8076-1931

https://www.ncbi.nlm.nih.gov/pubmed/25274446

78

Basic Science Departments

Clinical Science Departments

Duke

Duke Cancer Institute

Duke Human Vaccine Institute

Immunology

Institutes and Centers

Medicine

Medicine, Duke Human Vaccine Institute

Molecular Genetics and Microbiology

School of Medicine

Staff

Surgery

Surgery, Surgical Sciences

Published online

11