Viral evolution and transmission
The knowledge of the pathogenic mechanisms of infection and disease guide the development of intervention and prevention strategies and new HIV vaccine candidates. At this scope the group focuses mainly on models as mother-to-child transmission of HIV and disease progression in children and adults. In specific Viral evolution and transmission Unit determines the pathways of HIV within the intestinal mucosa, which is the site of viral entry, replication and persistence.
Our main research interests are:
1. The mucosa, the main portal of entry of HIV via all routes of transmission, is the site of major immune subversion early after infection. Data indicate that Dendritic cells (DC) are an early target for HIV and may become a source of virus for the surrounding cells affecting in turn innate and adaptive immune responses. Therefore the group studies with sophisticated imaging technology in vitro and ex vivo: i) the molecular mechanism driving the migration of HIV through the intestinal epithelial barrier; ii) the cellular targets in the mucosa, in specific macrophages and DCs, to identify the possible pathways to invade the tissue and disseminate to other organs; iii) the involvement of DCs and their functional properties in mediating adaptive immune responses at mucosal level; and iv) the role of antibodies with different effector functions in changing the pathways of the virus.
2. The antibody response controlling HIV, as the desirable and ultimate immune response induced by an HIV vaccine. The unit focuses its attention on selected models as mother-to-child transmission of HIV-1 or HIV infected patients controlling the disease or the virus, called Elite and Virus controller. Data show that infected children with slow progression of disease and Elite controllers develop neutralizing antibody and ADCC. Therefore the group: i) characterizes the specificity of these antibody responses to identify relevant targets for a vaccine; ii) developes new approaches to test antibody responses; and iii) adoptes the immunological analysis in preclinical (in rabbits and macaques) and clinical vaccines studies to identify predictive signatures for the development and prioritization of new HIV-1 vaccine candidates.
Agricola J, Munseri PJ, Nilsson C, Bakari M, Aboud S, Lyamuya EF, Tecleab T, Liakina V, Scarlatti G, Robb, ML, Earl PL, Moss B, Wahren B, Mhalu F, Ferrari G, Sandstrom E, Biberfeld G. Three-year durability of immune responses induced by HIV-DNA and HIV-modified vaccinia virus Ankara and effect of a late HIV- MVA boost in Tanzanian volunteers. AIDS Res Hum Retroviruses. 2017 Aug;33(8):880-888.
Le Grand R, Dereuddre-Bosquet N, Dispinseri S, Gosse L, Desjardins D, Shen X, Tolazzi M, Ochsenbauer C, Saidi H, Tomaras G, Prague M, Barnett SW, Thiebaut R, Cope A, Scarlatti G, Shattock RJ. Superior efficacy of a human immunodeficiency virus vaccine combined with antiretroviral prevention in simian-human immunodeficiency virus-challenged nonhuman primates. J Virol. 2016 May 12;90(11):5315-28.
Pogliaghi M, Ripa M, Pensieroso S, Tolazzi M, Chiappetta S, Nozza S, Lazzarin A, Tambussi G, Scarlatti G. Beneficial effects of cART initiated during primary and chronic HIV-1 infection on immunoglobulin-expression of memory B-Cell subsets. PLoS One 2015 Oct 16;10(10):e0140435.
Palma P, Romiti ML, Montesano C, Santilli V, Mora N, Aquilani A, Dispinseri S, Tchidjou HK, Montano M, Eriksson LE, Baldassari S, Bernardi S, Scarlatti G, Wahren B, Rossi P. Therapeutic DNA vaccination of vertically HIV-infected children: report of the first pediatric randomised trial (PEDVAC). PLoS One. 2013 Nov 28;8(11):e79957.
Cavarelli M, Foglieni C, Rescigno M, Scarlatti G. R5 HIV 1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5. EMBO Mol Med. 2013 May; 5(5):7 6-94.
Pensieroso S, Galli L, Nozza S, Ruffin N, Castagna A, Tambussi G, Hejdeman B, Misciagna D, Riva A, Malnati M, Chiodi F, Scarlatti G. B-cell subset alterations and correlated factors in HIV-1 infection. AIDS 2013 May 15;27(8):1209-17.
Heyndrickx L, Heath A, Sheik-Khalil E, Alcami J, Bongertz V, Jansson M, Malnati M, Montefiori D, Moog C, Morris L, Osmanov S, Polonis V, Ramaswamy M, Sattentau QJ, Tolazzi M, Schuitemaker H, Willems B, Wrin T, Fenyö EM, Scarlatti G. International network for comparison of HIV neutralization assays: The NeutNet Report II. PLoSOne 2012, 7 (5): e364338.
Sabin C, Corti D, Buzon V, Seaman MS, Lutje Hulsik D, Hinz A, Vanzetta F, Agatic G, Silacci C, Mainetti L, Scarlatti G, Sallusto F, Weiss RA, Lanzavecchia A, Weissenhorn W. Crystal structure and size-dependent neutralization properties of HK20, a human monoclonal antibody binding to the highly conserved heptad repeat 1 of gp41. PLoS Pathogens 2010 Nov 18;6(11):e1001195.
Cavarelli M, Karlsson I, Ripamonti C, Plebani A, Fenyo EM, Scarlatti G. Flexible use of CCR5 in the absence of CXCR4 use explains the immune deficiency in HIV-1 infected children. AIDS. 2010 Oct 23;24(16):2527-33.
Scarlatti G, Tresoldi E, Björndal A, Fredriksson R, Colognesi C, Deng HK, Malnati M, Plebani A, Siccardi AG, Littman DR, Fenyö EM, Lusso P. In vivo evolution of HIV-1 coreceptor usage and sensitivity to chemokine-mediated suppression. Nature Med 1997; 3: 1259-1265.