title: Humoral responses to HIVconsv induced by heterologous vaccine modalities in rhesus macaques.
abstract: Vaccines delivering T cell immunogen HIVconsv vectored by plasmid DNA, non-replicating simian adenovirus and non-replicating modified vaccinia virus Ankara (MVA) are under clinical evaluation in phase I/IIa trials in UK, Europe, and Africa. While these vaccines aim to induce effector T cell responses specific for HIV-1, we here characterized the humoral responses induced by HIVconsv administration to macaques using six different vaccine modalities: plasmid DNA, human adenovirus serotype 5, simian adenovirus serotype 63, MVA, Semliki Forest virus replicons, and adjuvanted overlapping synthetic long peptides (SLP). We found that only the SLP formulation, but none of the genetic vaccine platforms induced antibodies recognizing linear HIVconsv epitopes, median 32/46 SLP.HIVconsv peptides. These antibodies bound to 15-mer and SLP peptides, recombinant gp120 and trimeric gp140 of HIV-1 Bal, YU2, JRFL, and UG037, but failed to react with HIV-1 Bal and IIIB virions and HIV-1 Bal- and IIIB-infected human cells, and consequently failed to induce neutralizing antibodies. The HIVconsv immunogen contains conserved regions derived from Gag, Pol, Vif, and Env proteins of HIV-1, and antibodies induced by the SLP.HIVconsv vaccination resulted in positive signals in routine HIV-1 tests. Thus, only HIVconsv delivered by SLP resulted in seroconversion, an observation that provides important guidance for recruiting volunteers into future clinical trials. Furthermore, our data confirms that vaccine delivery by SLP induces humoral as well as cellular immune responses and could be considered for inclusion in future vaccine regimens where this is required.
authors.affiliation: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive Oxford, OX3 7DQ, UK.
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Borthwick
authors.affiliation: Nuffield Department of Medicine, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Oxford, OX3 9DS, UK.
authors.forename: Maximillian
authors.initials: M
authors.lastname: Rosario
authors.affiliation: Nuffield Department of Medicine, The Sir William Dunn School of Pathology, University of Oxford, South Parks Road Oxford, OX1 3RE, UK.
authors.forename: Torben
authors.initials: T
authors.lastname: Schiffner
authors.affiliation: Nuffield Department of Medicine, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Oxford, OX3 9DS, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Bowles
authors.affiliation: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive Oxford, OX3 7DQ, UK.
authors.forename: Tina
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Liljeström
authors.affiliation: Nuffield Department of Medicine, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Oxford, OX3 9DS, UK.
authors.forename: Guillaume E
authors.initials: GE
authors.lastname: Stewart-Jones
authors.affiliation: Departement of Immunohematology and Blood Transfusion, Leiden University Medical Centre Leiden, the Netherlands.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.affiliation: Departement of Immunohematology and Blood Transfusion, Leiden University Medical Centre Leiden, the Netherlands.
authors.forename: Cornelis J M
authors.initials: CJ
authors.lastname: Melief
authors.affiliation: Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive Oxford, OX3 7DQ, UK ; Nuffield Department of Medicine, MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, The John Radcliffe Oxford, OX3 9DS, UK.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Hanke
keywords: Antibodies; HIV vaccines; conserved regions; macaques; synthetic long peptides