Oral Abstract Session 01 - Global HIV Vaccine Enterprise

Plenary 03: New Concepts in Immune Induction
PL03.01
Follicular T Helper Cells in Vaccination and Lentivirus
Pathogenesis
R.A. Koup 1
1 Vaccine Research Center, Bethesda, MD, USA
Follicular CD4 T helper (TFH) cells promote the survival, isotype
switching and selection of high affinity memory B cells and plasma
cells. We investigated the phenotype, function, localization and
molecular profile of TFH in rhesus macaques. Similar to human
TFH, rhesus macaque TFH are characterized by a CCR7lowPD-
1highCTLA-4highICOShighCXCR4high phenotype and represent
a heterogeneous population with regard to cytokine function.
SIV infection leads to their expansion in lymphoid tissues, which
is associated with increased frequency of activated germinal
center B cells and SIV-specific antibodies. We have tested several
adjuvant preparations (in association with HIV Env vaccination) to
determine their potency in stimulating TFH cells, and any impact
upon the magnitude and quality of the antibody response.
We have also studied SHIV-infected monkeys and HIV-infected
humans to determine the levels and duration of lentivirus
antigen persistence that are associated with the induction of TFH
and broadly neutralizing antibody responses.
PL03.02
Plenary Sesions
Maturation Pathways of Broad Neutralizing
Antibodies: Blueprints for Vaccine Design
B. Haynes 1
1 Duke University Medical Center, Durham, NC, USA
Most broad neutralizing antibodies (bnAbs) share one of several
unusual characteristics: long heavy chain complementarity
determining regions, high levels of somatic mutations,
polyreactivity and VH restricted usage. All of these antibody
characteristics reflect traits that disfavor bnAb induction.
Antibody clonal lineages are being elucidated from chronically
HIV-1 infected subjects who make bnAbs to define bnAb
maturation pathways, and to design new prime, boost vaccine
regimens based on bnAb lineages. For vaccine induction of
bnAbs that are controlled by immune tolerance, deletional
mechanisms must be incomplete, and the remaining bnAb B cells
must be able to be activated by immunogens to make clinically
relevant levels of plasma antibodies. This talk will discuss lessons
learned from the study of bnAb clonal lineages and report results
of immunization strategies to stimulate anergic bnAb B cells.
AIDS Vaccine 2012
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PLENARY SESSIONS