title: Aggregate complexes of HIV-1 induced by multimeric antibodies.
abstract: 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.
authors.affiliation: Center for Infection, Department of Cellular and Molecular Medicine, St George's, University of London, London, SW17 0RE, UK. dstieh@northwestern.edu.|Current address: Department of Cellular and Molecular Biology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 60611, USA. dstieh@northwestern.edu.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stieh
authors.affiliation: Mucosal Infection & Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary's Campus, London, W2 1PG, UK. d.king@imperial.ac.uk.
authors.forename: Deborah F
authors.initials: DF
authors.lastname: King
authors.affiliation: Mucosal Infection & Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary's Campus, London, W2 1PG, UK. k.klein11@imperial.ac.uk.
authors.forename: Katja
authors.initials: K
authors.lastname: Klein
authors.affiliation: Duke Human Vaccine Center, Duke University Medical Center, Durham, NC, 27710, USA. ping.liu@duke.edu.|Current address: Division of Swine Infectious Diseases, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. ping.liu@duke.edu.
authors.forename: Pinghuang
authors.initials: P
authors.lastname: Liu
authors.affiliation: Duke Human Vaccine Center, Duke University Medical Center, Durham, NC, 27710, USA. sxshen@duke.edu.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Duke Human Vaccine Center, Duke University Medical Center, Durham, NC, 27710, USA. kkhwang@duke.edu.
authors.forename: Kwan Ki
authors.initials: KK
authors.lastname: Hwang
authors.affiliation: Duke Human Vaccine Center, Duke University Medical Center, Durham, NC, 27710, USA. gflmp@duke.edu.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Duke Human Vaccine Center, Duke University Medical Center, Durham, NC, 27710, USA. id.montefiori@duke.edu.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke Human Vaccine Center, Duke University Medical Center, Durham, NC, 27710, USA. hayne002@mc.duke.edu.
authors.forename: Barton
authors.initials: B
authors.lastname: Haynes
authors.affiliation: Faculty of Tropical Medicine, Mahidol, Thailand. punnee.pit@mahidol.ac.th.
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.affiliation: Faculty of Tropical Medicine, Mahidol, Thailand. tmjkk@mahidol.ac.th.
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. Sorachain@afrims.org.
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.affiliation: Ministry of Public Health, Bangkok, Thailand. supachai@health.moph.go.th.
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.affiliation: Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America. nmichael@hivresearch.org.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America. mrobb@hivresearch.org.
authors.forename: Merlin L
authors.initials: ML
authors.lastname: Robb
authors.affiliation: Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America. jkim@hivresearch.org.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Duke Human Vaccine Center, Duke University Medical Center, Durham, NC, 27710, USA. thomas.denny@duke.edu.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Denny
authors.affiliation: Duke Human Vaccine Center, Duke University Medical Center, Durham, NC, 27710, USA. georgia.tomaras@duke.edu.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Mucosal Infection & Immunity Group, Section of Infectious Diseases, Imperial College London, St Mary's Campus, London, W2 1PG, UK. r.shattock@imperial.ac.uk.
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G