Transcript AIDS Vaccines: The basics

AVAC
Global Advocacy for HIV Prevention
HIV Vaccines:
The basics
May 2016
Presentation Overview
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What is a vaccine?
How would an HIV vaccine work?
Where are we in the search?
What is needed now?
What is a vaccine?
• A substance that teaches the
immune system how to protect
itself against a virus or bacteria
• No effective HIV vaccine available
today
• HIV vaccines cannot cause HIV
• No vaccine is 100% effective
• Most vaccines licensed in the US
70%-95% effective
Why the interest in HIV vaccines?
• Proven prevention options have slowed HIV’s
spread – but thousands of people continue to get
infected daily
• There is a need for a range of HIV prevention
methods; there is no silver bullet
• Vaccines are one of the world’s most effective
public health tools
• Cost-effective – single or several doses likely
provide protection for years
How vaccines are crucial to ending HIV
Types of HIV vaccines
• Preventive vaccines
– Designed for people who are not infected with
HIV
– If effective, would reduce risk of infection
– May also reduce viral load set point after
infection
• Therapeutic vaccines
– Designed for people who are living with HIV
– If effective, would use the body’s immune system
to help control or clear HIV in the body
How do preventive vaccines work?
By teaching the body to recognize and fight a
pathogen
• Vaccine carries something that ‘looks and feels’
like the pathogen, but is not really the pathogen
• Body reacts by creating antibodies or killer cells and
a memory response
• Upon exposure to the ‘real’ pathogen, antibodies
and killer cells are waiting to respond and attack
Note: This is a general definition, not specific to HIV vaccines
How might preventive HIV vaccine work?
A preventive vaccine would teach the body to recognize
and fight HIV, should it be exposed
• Vaccine would carry a component that ‘looks and feels’ like
HIV, but is not HIV and cannot cause HIV infection
• Component might be a synthetic fragment of HIV known to
generate an immune response
• Body would react by creating antibodies and/or killer cells
and a memory response
• Upon possible exposure to HIV, antibodies and killer cells
would be waiting to prevent and/or control infection
Immune responses
Preventive HIV vaccines are meant to elicit two arms of
the immune system – humoral and cellular
(1) Humoral immunity
• Primary action of humoral
arm is creating antibodies
• Antibodies are Y-shaped
proteins developed in
response to a pathogen to
prevent infection
Immune responses
Preventive HIV vaccines are meant to elicit two
arms of the immune system – humoral and cellular
(2) Cellular immunity
• Cytotoxic T
lymphocytes and Thelper cells
• Cells recognize HIVinfected cells and kill
them
Preventing vs. controlling infection
HIV
PREVENT
ESTABLISHED
INFECTION?
*****
C
A
Vaccine
Administered
B
HAART
A. Lower Initial Peak of Viremia
B. Lower Set Point
Courtesy of HIV Vaccine Trials Network
C. Delay Progression
How have many vaccines been made?
• Live attenuated
vaccines (examples:
measles, mumps, and
rubella)
• Whole killed virus
vaccines (example:
influenza and rabies)
How are HIV vaccines made?
Recombinant vaccines
• DNA vaccines
• Vector vaccines
• Subunit vaccines
Do not contain HIV – only synthetic copies of
fragments of HIV that will create an immune response
but do not cause HIV infection
Developing an HIV vaccine is difficult
• Numerous modes of transmission
• HIV kills the very immune cells used in defending
the body against HIV
• HIV makes many copies of itself and mutates,
making itself unrecognizable to the immune system
• Mutation leads to different subtypes of the virus
throughout the world
Vaccine research in history
Duration between discovery of microbiologic cause of selected infectious diseases and development of a vaccine
Virus or bacteria
Year cause
discovered
Year vaccine
licensed
Years elapsed
Typhoid
1884
1989
105
Haemophilus Influenzae
1889
1981
92
Malaria
1893
None
–
Pertussis
1906
1995
89
Polio
1908
1955
47
Measles
1953
1995
42
Hepatitis B
1965
1981
16
Rotavirus
1973
1998
25
HPV
1974
2007
33
HIV
1983
None
–
Source: AIDS Vaccine Handbook, AVAC, 2005
HIV vaccine efficacy trial results
YEAR
PRODUCT/ CLADE/
TRIAL NAME
LOCATION
#
RESULT
2003
AIDSVAX B/B
VAX003
Canada,
Netherlands, Puerto
Rico, US
5,417 No effect
2003
AIDSVAX B/E
VAX004
Thailand
2,546 No effect
2007
MRK-Ad5 B
Step
Australia, Brazil,
Canada, Dominican
Republic, Haiti,
Jamaica, Peru,
Puerto Rico, US
3,000 Immunizations halted early for futility;
subsequent data analysis found potential for
increased risk of HIV infection among Ad5seropositive, uncircumcised men.
2007
MRK-Ad5 B
Phambili
South Africa
2009
ALVAC-HIV (vCP1521)
and AIDSVAX B/E
Thai Prime-Boost/RV
144
Thailand
2013
DNA and Ad5 A/B/C
HVTN 505
US
801 Immunizations halted based on Step result.
16,402 Modest effect (31.2%)
2,500 Immunizations halted early for futility; vaccine
regimen did not prevent HIV infection nor reduce
viral load among
vaccine recipients who became
www.avac.org/presentations
infected with HIV; follow-up continues.
Pox-Protein strategies
• In 2009 clinical study in Thailand (‘RV144’) showed evidence that a
vaccine can reduce HIV risk
– Pox-protein, prime-boost regimen using canary pox (ALVAC) and
manufactured HIV protein-GP120
– Moderately effective – 31% protection; not licensable
– Follow up research identified possible explanations for vaccinerelated protection and avenues for improvement
• New clinical trials launched by P5 in southern Africa in January 2015
– Modified regimen being tested in South Africa; potential efficacy
trial that might lead to licensure could start in late 2016
– Other regimens being tested for proof-of-concept, improved
responses
More information about Rv144 and the follow-up at: http://hivresearch.org/research.php?ServiceID=13
Antibody research
• 100s of broadly neutralizing antibodies (bNAbs) identified since 2009
– Work against majority of HIV strains
– Target limited number of sites on HIV surface
• Direct transfer of antibodies—passive immunization—being tested as
prevention, treatment, part of cure
– Multiple bNAbs tested in early clinical trials: www.bnaber.org
– Many show safety, tolerability, significant viral reduction among HIVpositive participants
– First large-scale study of bNAb VRC01 initiated April 2016 for proof of
concept, called AMP study: www.ampstudy.org
– Hope to increase potency of bNAbs, duration of responses
– Possible alternate delivery mechanisms to infusion, e.g. series of
subcutaneous shots
– Possible future combination bNAb approaches
Antibody research
Future priorities
• P5 – large-scale trials following RV144 results in South
Africa, possibly Thailand
• Janssen-sponsored product and clinical testing of ‘mosaic’
(cross-clade) based strategy
• Implications of AMP Study results for future of bNAb
research and vaccine design
• Advancement of candidates/strategies in smaller-scale trial
• Pre-clinical discovery and advancement of individual bNAbs
and combinations in clinical trials
• Continued identification of novel vectors, adjuvants and
other strategies for improved candidates
Advocates’ checklist
• Monitor timelines of clinical trials, especially delays
and the reasons for them
• Ensure diversity of approaches beyond pox-protein
strategy, exploring novel directions for vaccine
design
• Push for more stakeholder involvement, e.g., on
trial design, standard of prevention/care, decisionmaking on moving candidates through the clinical
pipeline
Key resources
• AVAC: www.avac.org/vaccines
• Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID)
o At Duke: www.chavi-id-duke.org
o At Scripps: www.cavi-id.org
• Collaboration for AIDS Vaccine Discovery: www.cavd.org
• Global HIV Vaccine Enterprise: www.vaccineenterprise.org
• HIV Px R&D Database (PxRD): www.data.avac.org
• HIV Vaccines & Microbicides Resource Tracking Working Group: www.hivresourcetracking.org
• HIV Vaccine Trials Network (HVTN): www.hvtn.org
• International AIDS Vaccine Initiative (IAVI): www.iavi.org
• Military HIV Research Program (MHRP): www.hivresearch.org
• NIAID: www.niaid.nih.gov/topics/hivaids/research/vaccines/Pages/default.aspx
• NIH Vaccine Research Center (VRC): www.vrc.nih.gov
• Pox-Protein Public-Private Partnership (P5): www.hivresearch.org/media/pnc/9/media.749.pdf
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