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Immunization with clinical HIV-1 env proteins induces broad antibody dependent cellular cytotoxicity-mediating antibodies in a rabbit vaccination model

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Show simple item record Karlsson, I. en_US Borggren, M. en_US Jensen, S. S. en_US Heyndrickx, L. en_US Stewart-Jones, G. en_US Scarlatti, G. en_US Fomsgaard, A. en_US 2019-06-04T12:21:40Z 2019-06-04T12:21:40Z 2018 en_US
dc.identifier.issn 0889-2229 en_US
dc.identifier.doi en_US
dc.identifier.other en_US
dc.identifier.other 52 en_US
dc.identifier.other ITG-B4A; DBM; U-VIROL; JIF; DOI; PDF; PMC; Abstract; ITMPUB; DSPACE65 en_US
dc.description.abstract The induction of both neutralizing antibodies and non-neutralizing antibodies with effector functions, for example, antibody-dependent cellular cytotoxicity (ADCC), is desired in the search for effective vaccines against HIV-1. In the pursuit of novel immunogens capable of inducing an efficient antibody response, rabbits were immunized with selected antigens using different prime-boost strategies. We immunized 35 different groups of rabbits with Env antigens from clinical HIV-1 subtypes A and B, including immunization with DNA alone, protein alone, and DNA prime with protein boost. The rabbit sera were screened for ADCC activity using a GranToxiLux-based assay with human peripheral blood mononuclear cells as effector cells and CEM.NKRCCR5 cells coated with HIV-1 envelope as target cells. The groups with the highest ADCC activity were further characterized for cross-reactivity between HIV-1 subtypes. The immunogen inducing the most potent and broadest ADCC response was a trimeric gp140. The ADCC activity was highest against the HIV-1 subtype corresponding to the immunogen. The ADCC activity did not necessarily reflect neutralizing activity in the pseudovirus-TZMbl assay, but there was an overall correlation between the two antiviral activities. We present a rabbit vaccination model and an assay suitable for screening HIV-1 vaccine candidates for the induction of ADCC-mediating antibodies in addition to neutralizing antibodies. The antigens and/or immunization strategies capable of inducing antibodies with ADCC activity did not necessarily induce neutralizing activity and vice versa. Nevertheless, we identified vaccine candidates that were able to concurrently induce both types of responses and that had ADCC activity that was cross-reactive between different subtypes. When searching for an effective vaccine candidate, it is important to evaluate the antibody response using a model and an assay measuring the desired function. en_US
dc.language English en_US
dc.relation.uri en_US
dc.subject HIV-1 en_US
dc.subject Viral diseases en_US
dc.subject Antibodies en_US
dc.subject Vaccine development en_US
dc.title Immunization with clinical HIV-1 env proteins induces broad antibody dependent cellular cytotoxicity-mediating antibodies in a rabbit vaccination model en_US
dc.type Article en_US
dc.citation.issue 2 en_US
dc.citation.jtitle AIDS Research and Human Retroviruses en_US
dc.citation.volume 34 en_US
dc.citation.pages 206-217 en_US
dc.citation.abbreviation AIDS Res Hum Retroviruses en_US

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