Hiv Tb Vaccines

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HIV AND TB VACCINES: HIV AND TB VACCINES: OBSTACLES MET AND OBSTACLES MET AND PROGRESSES MADE PROGRESSES MADE

description

The slideshow describes the vaccination strategies for the dreadly diseases HIV and Tuberculosis with a basic introduction to both the diseases.

Transcript of Hiv Tb Vaccines

HIV AND TB VACCINES: HIV AND TB VACCINES: OBSTACLES MET AND OBSTACLES MET AND PROGRESSES MADEPROGRESSES MADE

HIV discoveryHIV discovery

LUC MONTAGNIER BARRE SINOUSSI

HIV: Virion (Virus Particle)

gp120

gp41

viral envelope glycoproteins

lipid membrane of

envelope (host derived)

matrix (p17)viral core

(p24)

reverse transcriptase

viral RNA (ss) (2 copies)

HIV Virion StructureHIV Virion Structure

HIV HIV LifecycleLifecycle

T Cell

CD4

Course of HIV infection

0 3 6 9 12 1 2 3 4 5 6 7 8 9 10 11 12

Weeks Years

Primary Infection Seeding of lymphoid organs

Dissemination

0

250

500

750

1000

CD

4 co

unt (

cells

/µl)

Clinical Latency

Virus R

NA

(copies/ml)

AIDS (Opportunistic

Infections)

Modified from Sabin et al. JAIDS 23:172, 2000.

~0.1 log per year rise in HIV load

10

10

10

10

10

6

5

4

3

2

Course of HIV InfectionCourse of HIV Infection

Genes in HIV Genes in HIV GAGGAG

It makes various proteins necessary to protect the virus. It makes various proteins necessary to protect the virus. In HIV, it has three parts: MA (matrix), CA (capsid), and In HIV, it has three parts: MA (matrix), CA (capsid), and NC (nucleocapsid)NC (nucleocapsid)

POLPOLIt makes enzymes necessary for virus replication. In HIV, It makes enzymes necessary for virus replication. In HIV, it also has three parts: PR (protease), IN (endonuclease), it also has three parts: PR (protease), IN (endonuclease), and RT (reverse transcriptase)and RT (reverse transcriptase)

ENVENVThe envelope gene is also found in all retroviruses. It The envelope gene is also found in all retroviruses. It makes proteins for the envelope to the virus. In HIV, it makes proteins for the envelope to the virus. In HIV, it has two parts. SU (surface envelope, gp120) and TM has two parts. SU (surface envelope, gp120) and TM (transmembrane envelope, gp41)(transmembrane envelope, gp41)

Genes in HIV Genes in HIV

tattatThe transactivator gene influences the function of genes The transactivator gene influences the function of genes some distance away. It controls transactivation of all HIV some distance away. It controls transactivation of all HIV proteins.proteins.

revrevThe differential regulator of expression of virus protein The differential regulator of expression of virus protein genes. genes.

vifvifThe virus infectivity factor gene is required for infectivity The virus infectivity factor gene is required for infectivity as cell-free virus. as cell-free virus.

nefnefThe negative regulator factor retards HIV replication.The negative regulator factor retards HIV replication.

Genes in HIV Genes in HIV

vprvprThe virus protein R gene has an undetermined functionThe virus protein R gene has an undetermined function

vpuvpuThe virus protein U gene is required for efficient viral The virus protein U gene is required for efficient viral replication and release. It is found only in HIV-1replication and release. It is found only in HIV-1

vpxvpxThe virus protein X gene has an undetermined The virus protein X gene has an undetermined function. It is found only in HIV-2 and SIV function. It is found only in HIV-2 and SIV

Antigen Presenting Cells*“First-line Defense”*Involved in capturing antigen*Display ‘foreign’ antigens to activate T Cells

T Cells*Involved in the ‘killing’ ofvirus-infected cells*Adaptive Immunity

B Cells*Involved in making antibodies*Adaptive Immunity

NeutralisingAntibody

T cell Immunity

MucosalImmunity

InnateImmunity

The Ideal Vaccine

Requisites for a Requisites for a successful HIV vaccine:successful HIV vaccine:

AntibodiesAntibodies

Bind virus; neutralize or stop virus from Bind virus; neutralize or stop virus from infecting cells; eliminate virusinfecting cells; eliminate virus

Cytotoxic T lymphocytesCytotoxic T lymphocytes

Recognize cells infected with virus and Recognize cells infected with virus and kill those cellskill those cells

High mutability of virusHigh mutability of virus

No protective correlate definedNo protective correlate defined

Multiple clades all over the globeMultiple clades all over the globe

HIV VACCINES – WHY SUCCESS IS HARD?

Strains / Clades

C

CC

E

BB

B A,D E

CC

C

B

BB

2A-HO, N

B

Clades differ by around 20% of RNA and Protein sequence

What are the steps in What are the steps in Vaccine development?Vaccine development?

Phase I: 10-30 volunteers, 8-12 months

Phase II: 50-500 volunteers,18-24 months

Phase III: Thousands of volunteers, 3 or more years

What types of HIV vaccines are What types of HIV vaccines are being tested?being tested?

Peptide epitopes (protein fragments)

Live attenuated HIV

Whole, killed HIV

Naked DNA

Types of HIV vaccinesTypes of HIV vaccines

Recombinant Viral Proteins

Live bacterial vectors

Live Viral Vectors

Pseudovirions

HIV vaccines in clinical trials HIV vaccines in clinical trials for efficacy and for efficacy and immunogenicityimmunogenicity

Conclusions

Increasing understanding of how the immune response attempts to control HIV infection and how HIV evades this

Attempts to make a vaccine have been so far unsuccessful traditional approaches

Promising new approaches to prophylactic vaccines

Therapeutic vaccines may improve therapy

However, vaccines still several years away

TB statistics : 2006TB statistics : 2006

Globally, 9.2 million new cases Globally, 9.2 million new cases

1.7 million deaths from TB 1.7 million deaths from TB

0.7 million cases and 0.2 million deaths 0.7 million cases and 0.2 million deaths were in HIV-positive people were in HIV-positive people

WORLD TB CASESWORLD TB CASES

CASES OF TB PER 100,000 CITIZENS: >300 200-300

<50

100-200

N/A50-100

THE FORERUNNERSTHE FORERUNNERS

ROBERT KOCH ALBERT CALMETTE CAMILLE GUERIN

The BugThe Bug

TUBERCULOSISTUBERCULOSIS

BCG VACCINEBCG VACCINE

Deletion mutant of Deletion mutant of M.bovisM.bovis

Protects against childhood meningeal TB Protects against childhood meningeal TB

and disseminated TBand disseminated TB

Protection low in developing countriesProtection low in developing countries

Replacement BCG Replacement BCG vaccinesvaccines

rBCG30rBCG30

Hyperexpression of Ag85BHyperexpression of Ag85B

rBCG: rBCG: UreC:hly+UreC:hly+

Urease gene deleted and listeriolysin gene Urease gene deleted and listeriolysin gene incorporated BCG incorporated BCG

Boosting BCG vaccinesBoosting BCG vaccines

Ag85B-ESAT-6/TB10.4 fusion protein constructAg85B-ESAT-6/TB10.4 fusion protein construct

Mtb72f Mtb72f

Fusion protein of Mtb32 and Mtb39 proteinsFusion protein of Mtb32 and Mtb39 proteins

MV85AMV85A

Modified Vaccinia construct with Antigen 85AModified Vaccinia construct with Antigen 85A

TUBERCULOSIS VACCINESTUBERCULOSIS VACCINES

ConclusionsConclusions

TB vaccines show promising results in TB vaccines show promising results in clinical trialsclinical trials

Vaccine may be available for latently Vaccine may be available for latently infected individuals and naïve individualsinfected individuals and naïve individuals