title: Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate.
abstract: Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV envelopes of different clades. An epitope mapping analysis reveals that, on average, the binding is mostly focused on the C1, C2, V3, V5 and C5 regions. Immune sera show neutralization activity to Tier 1 isolates of different clades, demonstrating cross clade neutralizing activity which needs to be further broadened by possible structural modifications of the clade A gp14094UG018. Our results provide a rationale for the design and evaluation of immunogens and the clade A gp14094UG018 shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity.
authors.affiliation: Molecular Biology and Viral Oncogenesis Unit, Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Pascale" - IRCCS, Naples, Italy.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Visciano
authors.forename: Maria
authors.initials: M
authors.lastname: Tagliamonte
authors.forename: Guillaume
authors.initials: G
authors.lastname: Stewart-Jones
authors.forename: Leo
authors.initials: L
authors.lastname: Heyndrickx
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Marianne
authors.initials: M
authors.lastname: Jansson
authors.forename: Anders
authors.initials: A
authors.lastname: Fomsgaard
authors.forename: Berit
authors.initials: B
authors.lastname: Grevstad
authors.forename: Meghna
authors.initials: M
authors.lastname: Ramaswamy
authors.forename: Franco M
authors.initials: FM
authors.lastname: Buonaguro
authors.forename: Maria Lina
authors.initials: ML
authors.lastname: Tornesello
authors.forename: Priscilla
authors.initials: P
authors.lastname: Biswas
authors.forename: Gabriella
authors.initials: G
authors.lastname: Scarlatti
authors.forename: Luigi
authors.initials: L
authors.lastname: Buonaguro
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000145:classification; D006801:Humans; D056724:Immunity, Humoral; D007114:Immunization; D009500:Neutralization Tests; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology; D014454:Uganda; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D011994:Recombinant Proteins; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1