Università della Svizzera italiana

Conformational occlusion of blockade antibody epitopes, a novel mechanism of GII.4 human norovirus immune evasion

Lindesmith, Lisa C. ; Mallory, Michael L. ; Debbink, Kari ; Donaldson, Eric F. ; Brewer-Jensen, Paul D. ; Swann, Excel W. ; Sheahan, Timothy P. ; Graham, Rachel L. ; Beltramello, Martina ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: mSphere, 2018, vol. 3, no. 1, p. e00518-17

Extensive antigenic diversity within the GII.4 genotype of human norovirus is a major driver of pandemic emergence and a significant obstacle to development of cross- protective immunity after natural infection and vaccination. However, human and mouse monoclonal antibody studies indicate that, although rare, antibodies to conserved GII.4 blockade epitopes are generated. The mechanisms by...

Università della Svizzera italiana

Serum immunoglobulin a cross-strain blockade of human noroviruses

Lindesmith, Lisa C. ; Beltramello, Martina ; Swanstrom, Jesica ; Jones, Taylor A. ; Corti, Davide ; Lanzavecchia, Antonio ; Baric, Ralph S.

In: Open forum infectious diseases, 2015, vol. 2, no. 3, p. ofv084

Background: Human noroviruses are the leading cause of acute viral gastroenteritis, justifying vaccine development despite a limited understanding of strain immunity. After genogroup I (GI).1 norovirus infection and immunization, blockade antibody titers to multiple virus-like particles (VLPs) increase, suggesting that GI cross-protection may occur. Methods: Immunoglobulin (Ig)A was purified...

Università della Svizzera italiana

The neonatal Fc receptor (FcRn) enhances human immunodeficiency virus type 1 (HIV-1) transcytosis across epithelial cells

Gupta, Sandeep ; Gach, Johannes S. ; Becerra, Juan C. ; Phan, Tran B. ; Pudney, Jeffrey ; Moldoveanu, Zina ; Joseph, Sarah B. ; Landucci, Gary ; Supnet, Medalyn Jude ; Ping, Li-Hua ; Corti, Davide ; Moldt, Brian ; Hel, Zdenek ; Lanzavecchia, Antonio ; Ruprecht, Ruth M. ; Burton, Dennis R. ; Mestecky, Jiri ; Anderson, Deborah J. ; Forthal, Donald N.

In: Plos pathogens, 2013, vol. 9, no. 11, p. e1003776

The mechanisms by which human immunodeficiency virus type 1 (HIV-1) crosses mucosal surfaces to establish infection are unknown. Acidic genital secretions of HIV-1-infected women contain HIV-1 likely coated by antibody. We found that the combination of acidic pH and Env- specific IgG, including that from cervicovaginal and seminal fluids of HIV-1-infected individuals, augmented transcytosis...

Università della Svizzera italiana

Immunogenetic mechanisms driving norovirus GII.4 antigenic variation

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

In: Plos pathogens, 2012, vol. 8, no. 5, p. e1002705

Noroviruses are the principal cause of epidemic gastroenteritis worldwide with GII.4 strains accounting for 80% of infections. The major capsid protein of GII.4 strains is evolving rapidly, resulting in new epidemic strains with altered antigenic potentials. To test if antigenic drift may contribute to GII.4 persistence, human memory B cells were immortalized and the resulting human monoclonal...

Università della Svizzera italiana

In-depth analysis of the antibody response of individuals exposed to primary dengue virus infection

Alwis, Ruklanthi de ; Beltramello, Martina ; Messer, William B. ; Sukupolvi-Petty, Soila ; Wahala, Wahala M. P. B. ; Kraus, Annette ; Olivarez, Nicholas P. ; Pham, Quang ; Brian, James ; Tsai, Wen-Yang ; Wang, Wei-Kung ; Halstead, Scott ; Kliks, Srisakul ; Diamond, Michael S. ; Baric, Ralph ; Lanzavecchia, Antonio ; Sallusto, Federica ; Silva, Aravinda M. de

In: Plos neglected tropical diseases, 2011, vol. 5, no. 6, p. e1188

Humans who experience a primary dengue virus (DENV) infection develop antibodies that preferentially neutralize the homologous serotype responsible for infection. Affected individuals also generate cross-reactive antibodies against heterologous DENV serotypes, which are non-neutralizing. Dengue cross-reactive, non-neutralizing antibodies can enhance infection of Fc receptor bearing cells and,...

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...