hiv vaccine development strategies

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


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


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)


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


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)


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


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


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


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?

hiv vaccine development strategies

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