title: Membrane bound Indian clade C HIV-1 envelope antigen induces antibodies to diverse and conserved epitopes upon DNA prime/protein boost in rabbits.
abstract: The partial success of RV144 human clinical trial demonstrated that ALVAC prime/envelope protein boost vaccine regimen may represent a promising strategy for the development of an effective HIV-1 vaccine. Our earlier study demonstrated that a trimeric HIV-1 envelope gp145 from an Indian clade C isolate elicited cross clade neutralizing antibodies primarily towards Tier 1 isolates. In the present study, we examined the immunogenicity of DNA prime/envelope protein boost vaccine in rabbits using gp160 DNA of the Indian clade C isolate with various cytoplasmic tail truncations and trimeric gp145 protein. Cytoplasmic tail mutants of gp160 exposed epitopes that reacted strongly with a number of broadly neutralizing human monoclonal antibodies against HIV-1. Overall, envelope specific titers were found to be similar in all rabbit groups with higher pseudovirus neutralization in protein only immunized rabbits. The complete linear epitope mapping of rabbit immune sera revealed strong binding to C1, C2, V3, C3 and C4 domains of gp145. Importantly, reactivity of gp41 ecto-domain peptides was observed in DNA prime/protein boost sera but not in the sera of rabbits immunized with protein alone. Moreover, membrane anchored but not soluble envelope encoding DNA immunization elicited antibodies against linear epitopes on the conserved gp41 ecto-domain. Together, these results suggest that priming with DNA encoding cytoplasmic domains of Env alters the quality of antibodies elicited following protein boost and hence may be utilized to generate protective immunity by HIV-1 vaccine.
authors.affiliation: Laboratory of Molecular Virology and Cell Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India.
authors.forename: Sneha Priya
authors.initials: SP
authors.lastname: Rangasamy
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, MD, USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Menon
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, MD, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Dhopeshwarkar
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, MD, USA.
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.affiliation: Advanced Bioscience Laboratories Inc., Rockville, MD, USA.
authors.forename: Kalyanaraman S
authors.initials: KS
authors.lastname: Vaniambadi
authors.affiliation: Laboratory of Molecular Virology and Cell Biology, Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, India. Electronic address: mahalingam@iitm.ac.in.
authors.forename: Sundarasamy
authors.initials: S
authors.lastname: Mahalingam
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D001666:Binding Sites, Antibody; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D019302:HIV Envelope Protein gp160 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D009500:Neutralization Tests; D011817:Rabbits; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D019444:Vaccines, DNA
keywords: AIDS; Antibodies; DNA prime; Rabbits; Vaccination