Transcript NHVREI Year 3 Planning HVTN Communications plans

Immune Strategies for
HIV Prevention
Dr L Stranix-Chibanda
UZ-UCSF Annual Research Day
17 April 2015
Outline
 Active immunisation
 Recent history of HIV vaccine
development – RV144 trial
 The P5 initiative and Uhambo
 Passive immunisation
 Monoclonal antibodies against HIV
 Immunoprophylaxis by gene transfer
Active Immunisation
 Administer an antigen and wait for the
immune system to respond
 Requires immune system capable of
responding
 Takes some time for response to develop
 If successful, results in long term protection
 Generally results in both antibody and T cell
responses
RV144 – study design
 Thailand,>16,000 healthy,
heterosexual, HIV negative adults
 Intervention 2004-2006, 3-year
follow-up concluded 2009
 Tested 2 HIV vaccines
 Prime: ALVAC HIV (vCP1521)
pox
 Boost: AIDSVAX B/E (gp120)protein
RV144 – proof of concept/2009
P5 &
Uhambo – a journey of hope
 Identify a product submitted for
regulatory approval and eventual
public health introduction.
Graphic: AVAC Report 2014/5
P5 &
Uhambo – a journey of hope
 Correlates of protection – AB & T-cell
Graphic: AVAC Report 2014/5
Passive Immunisation
 Administer pre-formed antibodies
 Does not require intact immune system
 Immediate levels of antibodies detectable
 Only lasts as long as the antibodies last
Passive immunisation is used to
prevent a variety of infections
 Polyclonal



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Rabies Immune Globulin (RIG)
Hepatitis B Immune Globulin (HBIG)
Varicella Zoster Immune Globulin (VZIG)
Tetanus Immune Globulin
 Monoclonal
 Respiratory Syncitial Virus (Paluvizimab)
 Anthrax
Monoclonal AB against HIV
 Developed a few in 1990’s
 Explosion in AB development >2008
 next-generation sequencing
 advances in in vitro B cell clonal
amplification
 high-throughput neutralisation assays
 Identification of monoclonal antibodies
from HIV-infected patients with broad
and potent neutralisation potential
Sites of Vulnerability for HIV Neutralisation
V1V2
PG9/16, CH01-04, PGT 141-145
V3/glycan
2G12, PGT125-128, PGT131135, 10-1074
membrane proximal domain
CD4 binding site
2F5, 4E10, CAP206-CH12, 10E8
B12, VRC01-03, PG04, HJ16
CH30-34, NIH45-46, 12A12,
VRC07, 3BNC17
Haynes et al. (2012) Nat.Biot. 5: 423-433
Kwong and Mascola et al. (2012) Immunity. 37: 412-425
Possible Roles for Monoclonals
 Strong pre-clinical evidence that
potent monoclonal antibodies (like
VRC01) could be important for
prevention and treatment of HIV.
 Prevention of vertical transmission
 Augment therapy in treated children and
adults
 Early treatment of infected infants
 Strategy for cure
Barin, Jourdain, Brunet et al. JID 2006
Antibody therapy
 Advantages
 Single or intermittent injection, does not
require daily meds, adherence
 Could prevent disease or modify disease
in those already infected
 If it works, it provides critical data to
inform the entire vaccine field
 Disadvantages
 Requires monthly injection
 Currently expensive
bnAB clinical trials VRC/NIH
 Phase 1 trial US, S Africa, Zim
 Single dose of SC VRC01 to high-risk
newborns at birth (0-72hr)
 In addition to the standard-of-care HIV
prevention regimens
 Verify safety
 Determine PK profile of 20mg/kg dose
 Proceed to 40mg/kg dose, if safe
 VRC601/602 in adults, ?pregnancy
Antibody summary
 Potent and broadly neutralizing
monoclonal antibodies provide a new
opportunity for HIV prevention (also
treatment / cure)
 If effective, antibody production can be
scaled up and altered to increase
duration of effect (> 1 month)
Immunoprophylaxis by gene
transfer (IGT)
 A form of gene therapy to modify the
DNA of patients to enable them to
produce antibodies that deactivate HIV
 Pre-clinical studies in monkeys/mice
 identify the genes that produce powerful
antibodies against disease
 create artificial versions of these genes
 insert them into viruses  inject muscle
 transfer the genetically engineered DNA to
the muscle cells  alter programming
In conclusion,
 Various immune approaches are being
explored against HIV infection
 Advancements in laboratory
techniques mean that the knowledge
base is expanding rapidly
 None are yet ready for clinical use
 Immune strategies are required to
guarantee a sustained end to the AIDS
pandemic
Acknowledgements
 UZ College of Health Sciences
 UZ-UCSF Collaborative Research
Programme
 HIV Vaccine Trials Network
 IMPAACT Network
 Dr C Cunningham and VRC