hiv vaccine development strategies
TRANSCRIPT
HIV Vaccine HIV Vaccine Development Development
StrategiesStrategies
Brian WellsBrian Wells
University of FloridaUniversity of Florida
October 15, 2003October 15, 2003
What is a vaccine?What is a vaccine?
Substance that teaches the body’s Substance that teaches the body’s immune system to defend itself from a immune system to defend itself from a particular threat (virus, bacteria, etc.)particular threat (virus, bacteria, etc.)
Could work in a few waysCould work in a few ways Prevent the virus in most peoplePrevent the virus in most people Prevent the virus in some peoplePrevent the virus in some people Prepare the immune system to block Prepare the immune system to block
continued infection and eliminate the virus continued infection and eliminate the virus (measles, mumps, polio)(measles, mumps, polio)
Delay or prevent the onset of illness or AIDSDelay or prevent the onset of illness or AIDS
Source: http://www.niaid.nih.gov/publications/pdf/HIVvaccinebrochure.pdf
Why a vaccine?Why a vaccine?
Best long term hope for controlling the Best long term hope for controlling the AIDS pandemicAIDS pandemic
800,000 – 900,000 infected in the U.S.800,000 – 900,000 infected in the U.S. 40,000 newly infected each year in U.S.40,000 newly infected each year in U.S. Globally, 14,000 infected every dayGlobally, 14,000 infected every day Each minute, 6 people under 25 are Each minute, 6 people under 25 are
infectedinfected Over 40,000,000 infected worldwideOver 40,000,000 infected worldwide Over 16,000,000 have already died Over 16,000,000 have already died
from HIV-related illnessfrom HIV-related illnessSource: http://www.cdc.gov/nchstp/od/news/At-a-Glance.pdf
What type of vaccine?What type of vaccine?
Preventative vs. TherapeuticPreventative vs. Therapeutic Multiple vaccines may be neededMultiple vaccines may be needed Preventative vaccine could stop the Preventative vaccine could stop the
spread of HIV but can not cure someone spread of HIV but can not cure someone who is already infected.who is already infected.
Therapeutic vaccine could be used to Therapeutic vaccine could be used to treat individuals with HIVtreat individuals with HIV
What works to prevent HIV infection may What works to prevent HIV infection may not necessarily work in individuals who not necessarily work in individuals who are already infectedare already infected
Challenges in developing a Challenges in developing a vaccinevaccine
HIV continually mutates and recombinesHIV continually mutates and recombines HIV infects helper T cells (difficult to design a HIV infects helper T cells (difficult to design a
vaccine that needs to stimulate the very cells vaccine that needs to stimulate the very cells that are targeted)that are targeted)
HIV can be transmitted as free virus and in HIV can be transmitted as free virus and in infected cellsinfected cells
Do not know what constitutes an effective Do not know what constitutes an effective immune responseimmune response
Lack a good animal model for vaccine testing Lack a good animal model for vaccine testing (but several studies have provided useful (but several studies have provided useful results) results)
Types of VaccinesTypes of Vaccines
Peptide EpitopesPeptide Epitopes Status: In Phase I trialsStatus: In Phase I trials Advantages: Simple and inexpensive to Advantages: Simple and inexpensive to
prepare; probably safeprepare; probably safe Disadvantages: Can accommodate Disadvantages: Can accommodate
limited amount of HIV genetic material; limited amount of HIV genetic material; stability challengesstability challenges
Ex: HIV peptidesEx: HIV peptides
Types of VaccinesTypes of Vaccines
DNADNA Status: In Phase I trialsStatus: In Phase I trials Advantages: Simple and inexpensive to Advantages: Simple and inexpensive to
prepareprepare Disadvantages: Some worry that integration Disadvantages: Some worry that integration
of HIV genes into human cells could harm of HIV genes into human cells could harm patients (no current evidence of this); patients (no current evidence of this); current vaccines elicit modest immune current vaccines elicit modest immune responsesresponses
Ex: Naked DNA containing one or more HIV Ex: Naked DNA containing one or more HIV genesgenes
Types of VaccinesTypes of Vaccines
Live vectorsLive vectors Status: In Phase I trialsStatus: In Phase I trials Advantages: Simple and inexpensive to Advantages: Simple and inexpensive to
prepare; probably safeprepare; probably safe Disadvantages: Can accommodate Disadvantages: Can accommodate
limited amount of HIV genetic material; limited amount of HIV genetic material; stability challengesstability challenges
Ex: Live bacterial vectors (harmless Ex: Live bacterial vectors (harmless bacteria with genes to produce HIV bacteria with genes to produce HIV proteins)proteins)
Types of VaccinesTypes of Vaccines
Combination of ElementsCombination of Elements Status: In Phase II TrialsStatus: In Phase II Trials Advantages: Should stimulate both Advantages: Should stimulate both
arms of immune responsearms of immune response Disadvantages: Current combinations Disadvantages: Current combinations
elicit modest immune responseselicit modest immune responses Ex: pure gp120 protein plus canarypox Ex: pure gp120 protein plus canarypox
vectorvector
Types of VaccinesTypes of Vaccines
Recombinant Viral ProteinsRecombinant Viral Proteins Status: In Phase II and Phase III trialsStatus: In Phase II and Phase III trials Advantages: Safe and simple to prepareAdvantages: Safe and simple to prepare Disadvantages: Vaccine-elicited Disadvantages: Vaccine-elicited
antibodies have failed to recognize HIV antibodies have failed to recognize HIV from patientsfrom patients
Ex: Viral surface proteins (i.e. gp120)Ex: Viral surface proteins (i.e. gp120)
Types of VaccinesTypes of Vaccines
PseudovirionsPseudovirions Status: Close to Phase I trialsStatus: Close to Phase I trials Advantages: Present HIV surface and Advantages: Present HIV surface and
internal proteins in a relatively natural internal proteins in a relatively natural conformationconformation
Disadvantages: Difficult to produceDisadvantages: Difficult to produce
Types of VaccinesTypes of Vaccines
RepliconsReplicons Status: Close to Phase I trialsStatus: Close to Phase I trials Advantages: Probably safe; can Advantages: Probably safe; can
accommodate several HIV genesaccommodate several HIV genes Disadvantages: Complicated to prepareDisadvantages: Complicated to prepare
Types of VaccinesTypes of Vaccines
Live-AttenuatedLive-Attenuated Status: Not under study in humans; Status: Not under study in humans;
being assessed in nonhuman primatesbeing assessed in nonhuman primates Advantages: Most closely mimics HIV; Advantages: Most closely mimics HIV;
gives excellent protection in animal gives excellent protection in animal modelsmodels
Disadvantages: Virus could potentially Disadvantages: Virus could potentially cause diseasecause disease
Types of VaccinesTypes of Vaccines
Whole-KilledWhole-Killed Status: Not under study in humansStatus: Not under study in humans Advantages: Might present HIV surface Advantages: Might present HIV surface
proteins in a relatively natural proteins in a relatively natural conformation depending on inactivation conformation depending on inactivation procedureprocedure
Disadvantages: Slight risk that Disadvantages: Slight risk that preparations might include some active preparations might include some active virus; difficult to produce in large virus; difficult to produce in large amountsamounts
AIDSVAX Phase III TrialAIDSVAX Phase III Trial
Produced by VaxGenProduced by VaxGen Phase III in U.S. and ThailandPhase III in U.S. and Thailand Bivalent vaccine composed of gp120 Bivalent vaccine composed of gp120
proteins from HIV-1 subtypes B and Eproteins from HIV-1 subtypes B and E Proven safe and effective for Proven safe and effective for
stimulating antibody production against stimulating antibody production against B and E (most common in Thailand)B and E (most common in Thailand)
However, what constitutes an effective However, what constitutes an effective immune response to HIV?immune response to HIV?
Questions?Questions?