Induction of HIV blocking anti-CCR 5 IgA in Peyers ’ s Patches 1 without histopathological alterations 2 3

1 Division of Immunology, Transplantation and Infectious Diseases, San Raffaele 9 Scientific Institute, Milan, Italy 10 2 Molecular Biosensor and Imaging Center, Carnegie Mellon University, Pittsburgh, 11 PA, US 12 3 Inserm, U1016, Institut Cochin, Paris, France 13 4 CNRS UMR 8104, Paris, France 14 5 Entrée Muqueuse du VIH et Immunité Muqueuse Institut Cochin, Univ. Paris 15 Descartes Cité Paris Sorbonne, Paris, France 16 6 Pathology Department, Mouse Histopathology Unit, San Raffaele Scientific 17 Institute, Milan, Italy 18 # Corresponding author 19 8 These authors contributed equally 20 21 22 Running title: HIV protective CCR5 specific IgA 23 24 25 Corresponding author: lopalco.lucia@hsr.it 26 27 28 29 JVI Accepts, published online ahead of print on 8 January 2014 J. Virol. doi:10.1128/JVI.03663-13 Copyright © 2014, American Society for Microbiology. All Rights Reserved.

[1]  L. Lopalco,et al.  Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes , 2013, PloS one.

[2]  O. Pabst.  New concepts in the generation and functions of IgA , 2012, Nature Reviews Immunology.

[3]  L. Lopalco,et al.  Virus like particle based strategy to elicit HIV-protective antibodies to the alpha-helic regions of gp41. , 2012, Virology.

[4]  L. Lopalco,et al.  Isotype modulates epitope specificity, affinity, and antiviral activities of anti–HIV-1 human broadly neutralizing 2F5 antibody , 2012, Proceedings of the National Academy of Sciences.

[5]  L. Lopalco,et al.  Protecting the initial site of viral entry: an alternative HIV vaccine target , 2011, Expert review of vaccines.

[6]  H. Garg,et al.  HIV ENV Glycoprotein-mediated Bystander Apoptosis Depends on Expression of the CCR5 Co-receptor at the Cell Surface and ENV Fusogenic Activity* , 2011, The Journal of Biological Chemistry.

[7]  L. Lopalco,et al.  Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. , 2011, Immunity.

[8]  L. Lopalco.  Natural anti-CCR5 antibodies in HIV-infection and -exposure , 2011, Journal of Translational Medicine.

[9]  M. Bruchez,et al.  Detection and Quantification of β2AR Internalization in Living Cells Using FAP-Based Biosensor Technology , 2010, Journal of biomolecular screening.

[10]  S. Plotkin.  Correlates of Protection Induced by Vaccination , 2010, Clinical and Vaccine Immunology.

[11]  J. Reynes,et al.  CCR5 antagonism in HIV infection: ways, effects, and side effects , 2009, AIDS.

[12]  W. Olson,et al.  CCR5 monoclonal antibodies for HIV-1 therapy , 2009, Current opinion in HIV and AIDS.

[13]  A. Telenti.  Safety concerns about CCR5 as an antiviral target , 2009, Current opinion in HIV and AIDS.

[14]  B. Chain,et al.  HIV blocking antibodies following immunisation with chimaeric peptides coding a short N-terminal sequence of the CCR5 receptor , 2008, Vaccine.

[15]  D. Peabody,et al.  Immunogenic display of diverse peptides on virus-like particles of RNA phage MS2. , 2008, Journal of molecular biology.

[16]  S. Kaveri,et al.  Infection of Macrophages and Dendritic Cells with Primary R5-Tropic Human Immunodeficiency Virus Type 1 Inhibited by Natural Polyreactive Anti-CCR5 Antibodies Purified from Cervicovaginal Secretions , 2008, Clinical and Vaccine Immunology.

[17]  L. Lopalco,et al.  Two Amino Acid Substitutions within the First External Loop of CCR5 Induce Human Immunodeficiency Virus-Blocking Antibodies in Mice and Chickens , 2008, Journal of Virology.

[18]  D. Montefiori,et al.  Protection of macaques against vaginal SHIV challenge by systemic or mucosal and systemic vaccinations with HIV-envelope , 2008, AIDS.

[19]  John P. Moore,et al.  Antiretroviral drug-based microbicides to prevent HIV-1 sexual transmission. , 2008, Annual review of medicine.

[20]  L. Lopalco,et al.  Natural mucosal antibodies reactive with first extracellular loop of CCR5 inhibit HIV-1 transport across human epithelial cells , 2007, AIDS.

[21]  L. Lopalco,et al.  Long-lasting CCR5 internalization by antibodies in a subset of long-term nonprogressors: a possible protective effect against disease progression. , 2006, Blood.

[22]  M Anthony Moody,et al.  Antibody polyspecificity and neutralization of HIV-1: a hypothesis. , 2006, Human antibodies.

[23]  Hideaki Shibata,et al.  Effects of Immunization with CCR5-Based Cycloimmunogen on Simian/HIVSF162P3 Challenge1 , 2006, The Journal of Immunology.

[24]  L. Lopalco,et al.  Induction of Murine Mucosal CCR5-Reactive Antibodies as an Anti-Human Immunodeficiency Virus Strategy , 2005, Journal of Virology.

[25]  D. Montefiori,et al.  Mucosal and systemic anti-HIV responses in rhesus macaques following combinations of intranasal and parenteral immunizations. , 2004, AIDS research and human retroviruses.

[26]  L. Lopalco,et al.  CCR5-specific mucosal IgA in saliva and genital fluids of HIV-exposed seronegative subjects. , 2004, Blood.

[27]  L. Bergmeier,et al.  CCR5 targeted SIV vaccination strategy preventing or inhibiting SIV infection. , 2004, Vaccine.

[28]  Paul S. Albert,et al.  Induction of Autoantibodies to CCR5 in Macaques and Subsequent Effects upon Challenge with an R5-Tropic Simian/Human Immunodeficiency Virus , 2004, Journal of Virology.

[29]  J. Binley,et al.  Redox-Triggered Infection by Disulfide-Shackled Human Immunodeficiency Virus Type 1 Pseudovirions , 2003, Journal of Virology.

[30]  Marc Parmentier,et al.  Multiple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies. , 2002, Molecular biology of the cell.

[31]  H. Kessler,et al.  Anti-CCR5 antibodies in sera of HIV-positive individuals. , 2001, Human immunology.

[32]  L. Lopalco,et al.  CCR5-Reactive Antibodies in Seronegative Partners of HIV-Seropositive Individuals Down-Modulate Surface CCR5 In Vivo and Neutralize the Infectivity of R5 Strains of HIV-1 In Vitro1 , 2000, The Journal of Immunology.

[33]  G Vassart,et al.  Multiple Charged and Aromatic Residues in CCR5 Amino-terminal Domain Are Involved in High Affinity Binding of Both Chemokines and HIV-1 Env Protein* , 1999, The Journal of Biological Chemistry.

[34]  H. Guy,et al.  Epitope Mapping of CCR5 Reveals Multiple Conformational States and Distinct but Overlapping Structures Involved in Chemokine and Coreceptor Function* , 1999, The Journal of Biological Chemistry.

[35]  E. Buratti,et al.  The neutralizing antibody response against a conserved region of human immunodeficiency virus type 1 gp41 (amino acid residues 731-752) is uniquely directed against a conformational epitope. , 1998, The Journal of general virology.

[36]  K. McCoy,et al.  The immune geography of IgA induction and function , 2008, Mucosal Immunology.

[37]  S. Kaveri,et al.  HIV-1 Dendritic Cells with Primary R 5-Tropic Milk Block Infection of Macrophages and Natural Antibodies to CCR 5 from Breast Belec and , 2005 .

[38]  E. Buratti,et al.  V3 loop core region serotyping of HIV-1 infected patients using the FHV epitope presenting system. , 1997, Journal of virological methods.

[39]  E. Buratti,et al.  Conformational display of two neutralizing epitopes of HIV-1 gp41 on the Flock House virus capsid protein. , 1996, Journal of immunological methods.

[40]  S. Arya,et al.  Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. , 1995, Science.

[41]  F. Baralle,et al.  A new epitope presenting system displays a HIV-1 V3 loop sequence and induces neutralizing antibodies. , 1995, Vaccine.

[42]  F. Vogel,et al.  A compendium of vaccine adjuvants and excipients. , 1995, Pharmaceutical biotechnology.