Oral Abstract Session 01 - Global HIV Vaccine Enterprise

Oral Abstract Session 07: B Cell Responses
OA07.05
Non-neutralizing IgG Anti-PID Antibodies Decreased
Viral Load Following High Dose Vaginal Challenge of
Non-human Primates
C. Moog 1 , N. Dereuddre-Bosquet 2 , M. Biedma 1 , S. Schmidt 1 ,
T. Decoville 1 , I. Mangeot 2 , S. Zolla-Pazner 3 , B. Vcelar 4 ,
D. Katinger 4 , V. Holl 5 , R. Le Grand 2
1 INSERM, Strasbourg, France; 2 CEA, Fontenay-aux-Roses,
France; 3 NYU, New York, NY, USA; 4 Polymun Scientific GmbH,
Vienna, Austria; 5 Covance, Geneva, Switzerland
Background: Fc-mediated inhibitory activity of neutralizing
antibodies has been shown to participate in HIV protection
(Hessell et al. 2007). In addition, a non-neutralizing antibody
F240 was found to partially protect macaques from SHIV vaginal
transmission (Moore et al., 2011). However, mechanisms
involved in this protection need further investigations. In this
study, two non-neutralizing antibodies have been selected on
the basis of their Fc-mediated inhibitory functions in vitro for
further analysis of their protective role on vaginal challenge in
non-human primate (NHP).
Methods: We have assessed and scored various in vitro
HIV-inhibitory activities of non-neutralizing antibodies: Fcmediated
inhibition of macrophages through phagocytosis
of immunecomplexes, ADCC in primary infected CD4+ T
lymphocytes by autologous NK cells, capture of native primary
virus particles. Efficacy of two anti-PID antibodies with high in
vitro functional scores has been tested in NHP. The combination
of two antibodies formulated in 1.6% HEC gel has been topically
applied in the vagina of macaques (n=6), 1 hour before vaginal
challenge with high dose (10 AID50) of SHIVSF162P3.Infection
was followed by assessing viral load in the plasma.
Results: Although unable to block virus entry at mucosal site as
all treated animals became persistently infected, the antibody
treated macaques have significant decrease of plasma viral load
(day 7, p=0.0479; day 14, p=0.0351, day 42: p=0.0370).
Conclusion: Decrease in viral load following antibody treatment
strongly suggests that non-neutralizing inhibitory antibodies
could interfere with early viral replication and dissemination
through Fc-mediated inhibitory functions. Additional studies will
be required to optimize this inhibition, and combined strategies
should be developed to assess the potential synergy between
neutralizing and non-neutralizing inhibitory antibodies.
Oral Abstract Sessions
OA07.06
Vaccine-Induced ADCC-Mediating Antibodies Target
Unique and Overlapping Envelope Epitopes
J. Pollara 1 , M. Bonsignori 1 , M. Moody 1 , M. Alam 1 , H. Liao 1 ,
K. Hwang 1 , J. Pickeral 1 , J. Kappes 2 , C. Ochsenbauer 2 ,
K. Soderberg 1 , T.C. Gurley 1 , D.M. Kozink 1 , D.J. Marshall 1 ,
J.F. Whitesides 1 , D. Montefiori 1 , J.E. Robinson 3 ,
J. Kaewkungwal 4 , S. Nitayaphan 5 , P. Pitisuttithum 6 ,
S. Rerks-Ngarm 7 , J. Kim 8 , N. Michael 8 , G. Tomaras 1 ,
B.F. Haynes 1 , G. Ferrari 1
1 Duke University, Durham, NC, USA; 2 University of Alabama
at Birmingham, Birmingham, AL, USA; 3 Tulane University
School of Medicine, New Orleans, LA, USA; 4 Tropical Hygiene,
Mahidol University, Bangkok, Thailand; 5 Armed Forces
Research Institute of Medical Sciences, Bangkok, Thailand;
6 Clinical Tropical Medicine, Mahidol University, Bangkok,
Thailand; 7 Department of Disease Control, Ministry of Public
Health, Nonthaburi, Thailand; 8 US Military HIV Research
Program, Rockville, MD, USA
Background: Antibody Dependent Cellular Cytotoxicity (ADCC)
may be a contributing factor of immune responses controlling
HIV-1 replication. Understanding the epitopes recognized by
ADCC-mediating antibodies is likely to be important for the
development of an effective AIDS vaccine. We characterized the
epitope specificity and breadth of the ADCC-mediating antibody
response elicited by the RV144 vaccine regimen.
Methods: Twenty-three monoclonal antibodies (mAbs) were
isolated from 6 vaccine recipients either from IgG + memory B cells
cultured at near clonal dilution for 14 days (n=115,200) followed
by sequential screenings of culture supernatants for HIV-1 gp120
Env binding, or from memory B cell (n=206,745) sorting for HIV-1
group M consensus gp140Con.S Env binding. Target cells infected
with infectious molecular clones expressing Clade A/E (CM235),
B (BaL), and C (DU422 and DU151) env were used to characterize
the specificity and breadth of the 23 mAbs that display ADCC
activity. We defined the epitope specificity of the isolated mAbs
by mapping with B.MN and/or AE.92TH023 linear peptides in
ELISA and with Fab-competition in ADCC assays.
Results: Linear mapping revealed that 2 mAbs recognized the
V2, and 1 mAb the V3 regions of the gp120. Nineteen (19)
mAbs recognized conformational epitopes overlapping the C1
A32 epitope; one mAb (CH20) recognized a conformational
epitope that was not blocked by any of the Fabs (A32, 19B, 17b)
utilized in our assay. Fourteen of the 20 mAbs directed against
conformational epitopes mediated ADCC against the clade B BaL
Env; 4 recognized the clade C DU151 Env and 1 recognized the
clade C DU422 Env.
Conclusion: The RV144 vaccine regimen induced broadly-reactive
ADCC Abs that recognized both unique and overlapping regions
of gp120. The mAbs with the greatest breadth may be useful for
passive protection trials in rhesus macaques. If protective in nonhuman
primates, the epitopes recognized by these mAbs may
inform immunogen design.
AIDS Vaccine 2012
73
ORAL ABSTRACT SESSIONS