Università della Svizzera italiana

Antibody-driven design of a human cytomegalovirus gHgLpUL128L subunit vaccine that selectively elicits potent neutralizing antibodies

Kabanovaa, Anna ; Perez, Laurent ; Lilleri, Daniele ; Marcandalli, Jessica ; Agatic, Gloria ; Becattini, Simone ; Preite, Silvia ; Fuschillo, Dario ; Percivalle,Elena ; Sallusto, Federica ; Gerna, Giuseppe ; Corti, Davide ; Lanzavecchia, Antonio

In: Proceedings of the national academy of sciences of the United States of America, 2014, vol. 111, no. 50, p. 17965-17970

The use of neutralizing antibodies to identify the most effective antigen has been proposed as a strategy to design vaccines capable of eliciting protective B-cell immunity. In this study, we analyzed the human antibody response to cytomegalovirus (human cytomegalovirus, HCMV) infection and found that antibodies to glycoprotein (g)B, a surface glycoprotein that has been developed as a HCMV...

Università della Svizzera italiana

Influenza hemagglutinin membrane anchor

Benton, Donald J. ; Nans, Andrea ; Calder, Lesley J. ; Turner, Jack ; Neu, Ursula ; Lin, Yi Pu ; Ketelaars, Esther ; Kallewaard, Nicole L. ; Corti, Davide ; Lanzavecchia, Antonio ; Gamblin, Steven J. ; Rosenthal, Peter B. ; Skehel, John J.

In: Proceedings of the national academy of sciences of the United States of America, 2018, vol. 115, no. 40, p. 10112-10117

Viruses with membranes fuse them with cellular membranes, to transfer their genomes into cells at the beginning of infection. For Influenza virus, the membrane glycoprotein involved in fusion is the hemagglutinin (HA), the 3D structure of which is known from X-ray crystallographic studies. The soluble ectodomain fragments used in these studies lacked the “membrane anchor” portion of the...

Università della Svizzera italiana

Particle conformation regulates antibody access to a conserved GII.4 norovirus blockade epitope

Lindesmith, Lisa C. ; Donaldson, Eric F. ; Beltramello, Martina ; Pintus, Stefania ; Corti, Davide ; Swanstrom, Jesica ; Debbink, Kari ; Jones, Taylor A. ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Journal of virology, 2014, vol. 88, no. 16, p. 8826-8842

GII.4 noroviruses (NoVs) are the primary cause of epidemic viral acute gastroenteritis. One primary obstacle to successful NoV vaccination is the extensive degree of antigenic diversity among strains. The major capsid protein of GII.4 strains is evolving rapidly, resulting in the emergence of new strains with altered blockade epitopes. In addition to characterizing these evolving blockade...

Università della Svizzera italiana

Within-host evolution results in antigenically distinct GII.4 noroviruses

Debbink, Kari ; Lindesmith, Lisa C. ; Ferris, Martin T. ; Swanstrom, Jesica ; Beltramello, Martina ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Journal of virology, 2014, vol. 88, no. 13, p. 7244–7255

Genogroup II, genotype 4 (GII.4) noroviruses are known to rapidly evolve, with the emergence of a new primary strain every 2 to 4 years as herd immunity to the previously circulating strain is overcome. Because viral genetic diversity is higher in chronic than in acute infection, chronically infected immunocompromised people have been hypothesized to be a potential source for new epidemic...

Università della Svizzera italiana

Human anti–HIV-neutralizing antibodies frequently target a conserved epitope essential for viral fitness

Pietzsch, John ; Scheid, Johannes F. ; Mouquet, Hugo ; Klein, Florian ; Seaman, Michael S. ; Jankovic, Mila ; Corti, Davide ; Lanzavecchia, Antonio ; Nussenzweig, Michel C.

In: Journal of experimental medicine, 2010, vol. 207, no. 9, p. 1995-2002

The identification and characterization of conserved epitopes on the HIV-1 viral spike that are immunogenic in humans and targeted by neutralizing antibodies is an important step in vaccine design. Antibody cloning experiments revealed that 32% of all HIV-neutralizing antibodies expressed by the memory B cells in patients with high titers of broadly neutralizing antibodies recognize one or ...

Università della Svizzera italiana

Isolation of human monoclonal antibodies that potently neutralize human cytomegalovirus infection by targeting different epitopes on the gH/gL/UL128-131A complex

Macagno, Annalisa ; Bernasconi, Nadia L. ; Vanzetta, Fabrizia ; Dander, Erica ; Sarasini, Antonella ; Revello, Maria Grazia ; Gerna, Giuseppe ; Sallusto, Federica ; Lanzavecchia, Antonio

In: Journal of Virology, 2010, vol. 84, no. 2, p. 1005-1013

Human cytomegalovirus (HCMV) is a widely circulating pathogen that causes severe disease in immunocompromised patients and infected fetuses. By immortalizing memory B cells from HCMV-immune donors, we isolated a panel of human monoclonal antibodies that neutralized at extremely low concentrations (90% inhibitory concentration [IC90] values ranging from 5 to 200 pM) HCMV infection of...

Università della Svizzera italiana

CCR6 is expressed on an IL-10-producing, autoreactive memory T cell population with context-dependent regulatory function

Rivino, Laura ; Gruarin, Paola ; Häringer, Barbara ; Steinfelder, Svenja ; Lozza, Laura ; Steckel, Bodo ; Weick, Anja ; Sugliano, Elisa ; Jarrossay, David ; Kühl, Anja A. ; Loddenkemper, Christoph ; Abrignani, Sergio ; Sallusto, Federica ; Lanzavecchia, Antonio ; Geginat, Jens

In: Journal of experimental medicine, 2010, vol. 207, no. 3, p. 565-577

Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10–producing memory T cells. Human CD4+CCR6+ memory T cells contained comparable numbers of IL-17– and IL-10–producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic...