Dr. Anthony Cristillo Presented at the International Conference on Clinical and Cellular Immunology Conference
Dr. Anthony Cristillo presented his research on, “Increased Antibody Breadth in Lupus Rabbits Immunized with an Envelope-Based HIV-1 DNA Prime/Protein Boost Vaccine” in Track 5:HIV at the Clinical and Cellular Immunology Conference. The abstract for Dr. Cristillo’s presentation follows:
A.D. Cristillo1, S. Whitney1, B. Lewis1, J. Livesay1, R. McLinden2 and V.S. Kalyanaraman1
1Advanced BioScience Laboratories Inc, Rockville, Maryland, USA; 2US Military HIV Research Program, HJF
To understand the role of altered B-cell repertoires and neutralizing antibodies of longer H-CDR3, we vaccinated lupus rabbits with an HIV-1 DNA prime/protein boost regimen. We hypothesized that immunization of these rabbits, with a noted defect in B-cell development and antibody selection, would give rise to antibodies of greater breadth and neutralization than would otherwise be noted due to their reactivity to self proteins, lipids or long H-CDR3s.
SLE (lupus) rabbits and New Zealand White (NZW) rabbits were immunized at weeks 0, 4 and 8 with plasmid DNA encoding HIV-1 V2/V3 mutant gp145 or C-tail truncated gp160. DNA–primed rabbits were then boosted intramuscularly with ribi-adjuvanted recombinant protein at weeks 22, 28 and 38. Binding antibody titers were assessed by ELISA, B-cell epitope mapping was performed by pepscan ELISA, and neutralizing antibody screens were conducted using a Tzm-b1 pseudo-virus assay.
Both lupus and NZW rabbits, primed with plasmid DNA (V2/V3mut or Q708) and boosted with adjuvanted protein (gp145-V2/V3mut), generated robust anti-gp145 ELISA titers. Lupus rabbits elicited either comparable or lower antibody titers compared to NZW rabbits when total anti-gp145 antibodies were assayed. However, specific antibody responses to the neutralizing epitopes, 2F5/4E10, were slightly elevated in lupus rabbits. Furthermore, epitope mapping revealed that broader antibody responses were elicited in lupus rabbits compared to NZW rabbits. Our findings suggest that an increased breadth of epitope responses can be achieved by immunizing animals with a defect in B cell development that could give rise to antibodies of longer H-CDR3 and neutralization.
Biography
Anthony Cristillo has completed his Ph.D. from Queen’s University in Kingston, Ontario, Canada and postdoctoral studies from the National Institutes of Health in Bethesda, Maryland. He is the Associate Director of Product Development at Advanced BioScience Laboratories, Inc. He has published more than 25 papers in peer reviewed journals with a focus on molecular and cellular immunology in addition to HIV vaccinology. He has also contributed to several textbooks in the areas of clinical and cellular immunology.
