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Immunization with Clinical HIV-1 Env Proteins Induces Broad Antibody Dependent Cellular Cytotoxicity-Mediating Antibodies in a Rabbit Vaccination Model.
- Source :
-
AIDS research and human retroviruses [AIDS Res Hum Retroviruses] 2018 Feb; Vol. 34 (2), pp. 206-217. Date of Electronic Publication: 2017 Nov 17. - Publication Year :
- 2018
-
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.NKR <subscript>CCR5</subscript> 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.
- Subjects :
- AIDS Vaccines administration & dosage
AIDS Vaccines isolation & purification
Animals
Antibodies, Neutralizing blood
Cross Reactions
Female
HIV Infections virology
HIV-1 isolation & purification
Humans
Immunization Schedule
Leukocytes, Mononuclear immunology
Male
Rabbits
Vaccines, DNA administration & dosage
Vaccines, DNA immunology
Vaccines, DNA isolation & purification
Vaccines, Subunit administration & dosage
Vaccines, Subunit immunology
Vaccines, Subunit isolation & purification
env Gene Products, Human Immunodeficiency Virus isolation & purification
AIDS Vaccines immunology
Antibody-Dependent Cell Cytotoxicity
HIV Antibodies blood
HIV-1 immunology
env Gene Products, Human Immunodeficiency Virus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1931-8405
- Volume :
- 34
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- AIDS research and human retroviruses
- Publication Type :
- Academic Journal
- Accession number :
- 28982260
- Full Text :
- https://doi.org/10.1089/AID.2017.0140