History of HIV HIV 1930 HIV-1 arises 1959 Earliest sero-positive 1981 AIDS emerges 1983 HIV-1 identified 1986 HIV-2 identified 1997 Advent of HAART 2006
Complacency High Risk Behavior Human Rights Abuses Stigma- tization Access To Care Sexism Ignorance Poverty Discrimin- ation Disem- powered Women Prejudice Denial Courtesy of Jim Hoxie
Is prevention better than cure ever?
What is "better?“
Vaccination against whooping cough has its dangers,
But these are negligible in comparison with whooping cough itself
HIV Treatment: Anti-virals
X X Reverse Transcription Inhibitors Protease Blockers
The Challenge of finding a cure for HIV
Highly active antiretroviral therapy ( HAART ) for the chronic suppression of HIV replication has been the major accomplishment in HIV/AIDS medicine
Many patients are now in their second decade of treatment , with levels of plasma HIV RNA below the limits of detection of clinical assays
Many patients are now enjoying a life-style little encumbered by symptoms or the side effects of medications, many of which require only once daily administration
HAART is no panacea .
Current treatments must be maintained for life
with treatment interruption resulting in the rapid rebound of replicating virus
Although drug resistance can emerge
Despite the prolonged suppression of HIV replication below the standard limits of detection for patients on HAART, ongoing viremia can be detected at levels of 1 to 50 copies per milliliter in the majority of patients
The origin of this viremia has not been fully characterized
The suboptimal penetration of many antiretrovirals into the central nervous system may also permit low levels of viral replication and/or release from stable viral reservoirs, resulting in neuropathology
There is already growing concern about increased rates of heart disease, diabetes, liver disease , and many forms of cancer in aging HIV-infected patients who are receiving treatment
the cost of HAART may be too much to sustain treatments on a global scale, as millions are affected
chronic suppressive therapy is required to contain persistent infection in reservoirs such as latently infected CD4+ lymphocytes and cells of the macrophage-monocyte lineage
HIV latency • Latently infected resting memory CD4+ T cells are the best characterized latent reservoir for HIV-1. • Less than 1 cell per 1,000,000 resting CD4+ T cells from patients on HAART harbor latent HIV-1 provirus. • Sequence of latent proviruses does not evolve , which suggests no ongoing viral replication. • Discontinuation of HAART allows viral relapse from latent reservoir.
• Patients successfully treated with HAART for longer than 10 years exhibit no appreciable decrease in the size of the latent reservoir.
• The persistence of latently infected memory CD4+ T lymphocytes precludes their elimination by HAART alone for the lifetime of the patient.
• Other drug-insensitive reservoirs, including brain, macrophages, and hematopoietic stem cells, may also exist.
• Latency is likely established and maintained by numerous blocks at multiple steps in the HIV-1 replicative pathway, which potentially complicates eradication strategies.
many lymphocytes can be visualized that produce small amounts of viral RNA, yet do not display markers of activation
Potential transcriptional blocks in HIV latency
Potential post-transcriptional blocks in HIV latency
Potential therapies to disrupt latent proviral HIV infection
3. Prostratin ( Homalanthus nutans )
4. HDAC inhibitors
Potential therapies to disrupt latent proviral HIV infection
Can Mechanisms That Drive Latency Be Therapeutically Exploited?
Activation from latency to completion of the replication cycle should result in lytic cell death of CD4+ T cells.
Purging persistent proviral infection
A vaccine that prevents cervical cancer, better therapies to treat malignancies
Prevention is better than Cure
HIV-1 Vaccines (Fields Virology)
The major obstacle to vaccine development is the tremendous sequence heterogeneity both within and among clades worldwide .
The development of an effective vaccine remains the best chance for ending the epidemic.
Vaccines from Bench to Clinic
Discovery or Pre-Clinical Phase
Usually the result of experimentation in academic, pure research or biotech labs
Data provide “ Proof of Principal ” and suggest commercialization of idea
Academic labs incapable of further product development
Idea should be patented to protect “intellectual property”
Patent can be licensed to drug companies for commercialization
Costs $600 million-$1 billion
Takes 8-10 years
Vaccines must be made employing “ good manufacturing practice (GMP)”
Cost and time needed to assure vaccine is safe and efficacious.
Begins with submission of an “ Investigational New Drug (IND) ” application to the FDA
FDA’s Center for Biologics Evaluation and Research (CBER) is responsible for regulating vaccines in USA
Successful completion of all 3 phases of clinical development can be followed by submission of a Biologic License Application (BLA)
Following review, the findings may be presented to FDA’s Vaccines and Related Biological Products Advisory Committee for advice to the agency regarding the safety and efficacy of the vaccine for the proposed indication
Vaccine approval also requires adequate labeling
FDA continues to monitor product and manufacturing of vaccine to ensure continuing safety
The challenge of developing an HIV vaccine spans the need for new basic research insights to product development to clinical trials.
The complexity of fostering and coordinating these efforts has led to the creation of:
1. major NIH intramural ( Vaccine Research Center )
2. NIH extramural ( Center for HIV/AIDS Immunology )
3. international, multi-institutional effort ( The Global HIV Vaccine Enterprise ).
Following submission of IND a candidate vaccine is tested in a small number ( 10-30) healthy human adult volunteers who are not at risk for the disease in question.
Main goal is safety and to a lesser extent immunogenicity involving different doses and different immunization schedules.
Phase 1 studies usually take 8-12 months and can be done in academic setting or biotech settings but need institutional
Phase 2 Studies
Involves a larger number of volunteers ( 50-500 ), usually a mixture of low-risk and higher risk individuals from the population where phase 3 studies will be done.
Main goal is to generate safety data as well as information for refining dosage and immunization schedule , vaccine formulations and lot consistency
May also provide preliminary data relative to efficacy
Trials usually take 18-24 months because of screening and enrolling large numbers of participants
Phase 3 Studies
The randomized, controlled clinical trial aimed at providing scientific evidence about the clinical performance of vaccines.
Involves 1000s of participants from high risk populations where individuals, having given informed consent, are randomized into test and control groups to be given vaccine or placebo in a blinded study to avoid bias.
The goal of phase 3 trials is to determine vaccine safety and efficacy in a large study population sample leading to licensure application
Phase 4 Trials
Phase 4 (phase IV) Phase 4 trials are done after a vaccine has been shown to work and has been granted a license . So they are looking at vaccines that are already available for doctors to prescribe, rather than new drugs that are still being developed.The main reasons pharmaceutical companies run phase 4 trials are to find out more about the side effects and safety of the vaccine , what the long term risks and benefits are, and how well the vaccine works when it is used more widely than in clinical trials
After a phase III trial
Distribution and access.
Phase IV effectiveness and public health impact measures.
Monitoring and data gathering.
Analysis and publication of results .
Barriers to the Optimal Use of Licensed Vaccines
Pregnancy and the application of licensed vaccines
Removal of vaccines from the marketplace:
Error in judging market size
U.S. single largest market for vaccines When reimbursement is denied vaccine availability throughout world may suffer
Need for New Vaccines
Sexually transmitted vaccines
Vector borne diseases
Other viruses,bacteria, and fungi
Phases on the development and evaluation of HIV vaccines Phase I Phase II Phase III Phase IV Preclinical phase
Animal protection experiments
20–50 HIV-negative volunteers (lower risk)
safety and immunogenicity
100s of HIV-negative volunteers (lower and higher risk)
safety and immunogenicity; and also
doses, routes of administration, different populations
1000s of HIV-negative volunteers (higher risk)
efficacy (against infection or against disease)
(how to use the vaccine for public health purposes )
How vaccines are developed? Basic research Preclinical development Clinical trials Phase I/II Phase III Safety, Immunogenicity Discovery Human research in vitro & animal studies Laboratory Exploration Efficacy Vaccine concept Experiments in primates Human trials 1 2 3 4 5 6 Safety, immunogenicity Likelihood of protection in humans 1: Recombinant Protein – 2: Synthetic Peptides – 3: Naked DNA 4. Live-recombinant vectors- 5: Whole inactivated virus – 6: Live attenuated virus
Why a HIV vaccine might be feasable? 1. Vaccination has been successful against other viral diseases . 2. Experimental HIV/SIV vaccines have protected chimpanzees/macaques . 3. Candidate HIV vaccines are immunogenic. 4. Some humans can regulate infection and/or HIV replication .
Approaches to AIDS vaccine designs
Current HIV vaccine strategies
(1) Traditional strategies:
Live attenuated viruses
Whole killed viruses
(2) Novel strategies
Plasmid DNA vaccines
Live recombinant vectors
What is immunity?
When the body is primed (armed) to resist infection and/or disease by the pathogen.
Two arms :
cellular (cytotoxic T cells or CTLs)
and humoral (antibodies) immunity
What is an HIV vaccine?
A substance that mimics the properties of the virus without causing infection.
A vaccine stimulates immune responses by teaching the immune system to recognise and defend against a disease-causing virus.
What is a Vaccine?
Vaccine vak - ´sen a substance that teaches the body’s immune system to recognize and protect against a disease caused by an infectious agent or virus
WHAT SHOULD AN HIV-1 VACCINE DO ?
Induce the body to make
protective antibodies and immune cells
to prevent infection
at mucosal sites (for sexually transmitted HIV)
lower viral load and stop progression to AIDS
But … HIV is particularly challenging because it infects exactly the immune system T cells that are supposed to protect you from infections.
Challenges in tha development of HIV-1 vaccine
Prophylactic HIV-1 vaccine might to be able to elicit humoral and cellular immunity
Vaccine that elicites only cellular immunity might can be used as a therapeutic vaccine
The goal of an HIV-1 vaccine would be either to prevent infection or to reduce viral loads and clinical disease progression after infection
Challenges in the development of a prophylactic HIV-1 vaccine
( 1 ) Extensive viral clade and sequence diversity .
( 2 ) Early establishment of latent viral reservoirs.
( 3 ) Immune correlates of protection unclear.
( 4 ) Viral evasion of humoral and cellular immune responses.
( 5 ) Antibody responses typically type-specific.
Challenges in the development of a prophylactic HIV-1 vaccine(cont.)
( 6 ) No method exists to elicit broadly reactive neutralizing antibodies.
( 7 ) Attenuated viruses unsafe for human use.
( 8 ) Lack of a small-animal model.
( 9 ) Little pharmaceutical interest.
Diversity (greatest hurdle)
The extraordinary worldwide diversity of HIV-1 presents perhaps the greatest hurdle.
Driven by the error prone reverse transcriptase, the HIV-1 M group has diversified into nine divergent clades as well as multiple circulating recombinant forms.
Amino acid sequences of Env can differ up to 20% within a particular clade and over 35% between clades
vaccine protection will necessarily be dependent on the capacity of immune responses to cross-react with highly heterologous viruses
HIV-1-specific humoral immunity
The HIV-1 Env glycoprotein is a trimer on the virion surface with extensive N-linked glycosylation that effectively shields many conserved epitopes from antibody recognition.
Highly immunogenic variable loops also elicit type-specific antibodies that may redirect humoral responses away from conserved regions.
In addition, key conserved regions, such as the binding site of the chemokine co-receptor, are only formed after Env binds its cellular receptor CD4 and undergoes an extensive conformational change
Current strategies to design vaccines to generate broadly neutralising antibodies
Current strategies to design vaccines to generate broadly neutralising antibodies
The first is to generate a candidate that mimics the shape of the mature trimeric Env complex on the virion's surface
The second is to produce antigen molecules that focus the immune response on cross-reactive immunodominant non-neutralising epitopes.
A third strategy is to produce stable intermediates in the HIV binding process that present conserved epitopes to elicit CD4-induced antibodies.
The final strategy is to produce epitope mimics of the broadly neutralising monoclonal antibodies, ascertained from structural studies of the MAb-Env complex
there are currently no vaccine candidates that are aimed at eliciting broadly reactive Env specific neutralizing antibodies in clinical trials.
Cellular immunity Experimental depletion of CD81 lymphocytes has been shown to abrogate immune control of simian immunodeficiency virus (SIV) replication in rhesus monkeys Polyfunctional T lymphocytes capable of performing multiple functions have been reported in long-term non-progressors
most licensed viral vaccines seem to function by controlling subclinical viral replication and by preventing clinical disease
Despite the urgent need for an HIV-1 vaccine, only two vaccine concepts have completed clinical efficacy studies so far
completed clinical efficacy studies
monomeric HIV-1 Env gp120 protein, and the aim of this strategy was to induce Env-specific humoral immune responses. In early-phase clinical trials, gp120 immunogens elicited type-specific binding antibodies but failed to induce broadly reactive neutralizing antibodies
The second vaccine concept that has completed clinical efficacy studies involved replication-incompetent recombinant adenovirus serotype 5 (rAd5) vectors expressing HIV-1 Gag, Pol and Nef . The aim of this strategy was to elicit HIV-1-specific cellular immune responses
phase 3 efficacy trials
trials sponsored by the biotechnology company VaxGen ,
these vaccine candidates afforded no detectable protective efficacy , indicating that these type-specific antibody responses were insufficient to protect against HIV-1 infection in humans
Another phase 3 study evaluating the efficacy of a recombinant canarypox vector prime/gp120 protein boost vaccine regimen is currently underway
Vaccine trials in South Africa
HVTN 503 (MRK Ad 5 polyvalent B), ‘ Phambili trial ’, started February 2007, ended September 2007 , 3000 participants
Approved in SA, waiting for US progress
SAAVI ( South African AIDS Vacine Initiative) (Phase I) - DNA / MVA (C) (2008?)
WHERE ARE WE NOW as SAAVI ?
Two Candidate Vaccines ready for Clinical Trials:
SAAVI DNA-C2 to be used as the primary vaccine
Two-component DNA vaccine comprising:
DNA expressing Gag-RT-Tat-Nef
DNA vaccine expressing truncated Env
SAAVI MVA-C to be used as the booster vaccine
Modified Vaccinia Ankara (MVA) Vaccine expressing Gag-RT-Tat-Nef and truncated Env = Boost
Vaccine phase 1 trials to begin 2007/8 (HVTN 073/SAAVI 102)
SAAVI-DNA-C2 and SAAVI-MVA-C for clinical trial
HIV Vaccine Trials Network ( HVTN )
An international collaboration of scientists and educators searching for an effective and safe HIV vaccine. The HVTN's mission is to facilitate the process of testing preventive vaccines against HIV/AIDS. Our organization conducts all phases of clinical trials, from evaluating experimental vaccines for safety and the ability to stimulate immune responses, to testing vaccine efficacy.
http://chi.ucsf.edu/vaccines Ongoing HVTN Trials: Phase II Protocol Number Status as of July 2008 Prime Boost Class Producer Product Name Adjuvant Class Producer Product Name Adjuvant HVTN 502/Merck 023 (Step) (n=3000) Closed to accrual Nonreplicating adenoviral vectors (clade B Gag-Pol-Nef) Merck MRKAd5 trivalent HVTN 503 (n=801) Closed to accrual Nonreplicating adenoviral vectors (clade B Gag-Pol-Nef) Merck MRKAd5 trivalent
http://chi.ucsf.edu/vaccines Ongoing HVTN Trials: Phase I (Slide 1 of 2) Protocol Number Status as of July 2008 Prime Boost Class Producer Product Name Adjuvant Class Producer Product Name Adjuvant HVTN 050/Merck 018 (n=435) Closed to accrual Nonreplicating adenoviral vector (clade B Gag) Merck MRKAd5 HIV-1 Gag HVTN 063 (n=156) Closed to accrual DNA plasmid (clade B Gag) Wyeth GENEVAX gag -2962 DNA plasmid cytokine ( IL-15) + bupivacaine Peptides ( poly- epitopic: clade B Env, Gag, Nef ) Wyeth Wyeth multiepitope CTL peptide vaccine RC529-SE, GM-CSF Or DNA plasmids (clade B Gag) Wyeth GENEVAX gag -2962 DNA plasmid cytokine (IL-12) + bupivacaine HVTN 065 (n=120) Closed to accrual DNA plasmid ( clade B Gag, Pro, RT, Env, Tat, Rev, Vpu ) GeoVax HIVB DNA pGA2/JS7 MVA vector (clade B Gag, Pol, Env) GeoVax MVA-HIV 62
http://chi.ucsf.edu/vaccines Ongoing HVTN Trials: Phase I (Slide 2 of 2) Protocol Number Status as of July 2008 Prime Boost Class Producer Product Name Adjuvant Class Producer Product Name Adjuvant HVTN 067 (n=108) Closed to accrual DNA plasmid (polyepitopic: Gag, Pol, Vpr, Nef, Rev, Env) Pharmexa-Epimmune EP HIV-1233 MVA vector (poly-epitopic: Gag, Pol, Vpr, Nef, Rev, Env) Bavarian-Nordic MVA-mBN32 HVTN 069 (n=90) Closed to accrual DNA plasmids (clade B Gag-Pol-Nef; clade A,B,C Env) given by IM route NIH VRC VRC-HIVDNA-009 Nonreplicating adenoviral vectors (clade B Gag-Pol; clade A,B,C Env) given by SC or ID vs IM route NIH VRC VRC-ADV-014 HVTN 070 (n=120) Enrolling DNA plasmids (clade B Gag, Pol, Env) Univ. of Pennsyl-vania (D. Weiner) PENNVAX-B DNA plasmid cytokines (IL-12 or IL-15) + bupivacaine HVTN 071 (n=35) Closed to accrual Nonreplicating adenoviral vectors (clade B Gag, Pol, Nef) Merck MRKAd5
http://chi.ucsf.edu/vaccines Planned HVTN Trials: Phase I, July 2008 Protocol Number Anticipated Start Date Prime Boost Class Producer Product Name Adjuvant Class Producer Product Name Adjuvant HVTN 073 (n=96) Q3 2008 DNA plasmids (clade C Gag, RT, Tat, Nef; clade C Env) SAAVI SAAVI DNA-C2 MVA vector (clade C Gag, RT, Tat, Nef; clade C gp150CT) SAAVI SAAVI MVA-C HVTN 076 Q3 2008 DNA plasmids (clade B Gag, Pol, Nef; Clade A, B, C Env NIH VRC VRC-HIVDNA-016 Non-replicating adenoviral vectors (clade B Gag-Pol; clade A, B, C Env) NIH VRC VRC-ADV-014 HVTN 077 Q3 2008 DNA plasmids (clade A Env) NIH VRC VRC-HIVDNA044 Non-replicating adenoviral vectors , type 5 (clade A Env) NIH VRC VRC-HIVDNA038 OR OR Non-replicating adenoviral vector, type 35 (clade A Env) NIH VRC VRC-HIVADV027 Non-replicating adenoviral vector, type 35 (clade A Env) NIH VRC VRC-HIVADV027
http://chi.ucsf.edu/vaccines Completed HVTN Trials, July 2008 (Slide 1 of 5 ) Protocol Number Year Completed Prime Boost Class Producer Product Name Adjuvant Class Producer Product Name Adjuvant References HVTN 039 (n=110) 2003 Canarypox vector (clade B Env, Gag, Pro, RT, Nef) Sanofi Pasteur ALVAC vCP1452 (high-dose) Goepfert P, et al. J Infect Dis 2005; 192:1249-59 HVTN 041 (n=84) 2003 Protein (clade B Nef-Tat fusion protein + clade B Env subunit) GlaxoSmith Kline NefTat + gp120W61D AS02A Goepfert, P et al. Vaccine 2007 Jan 5;25(3):510-8 HVTN 203 (n=330) 2003 Canarypox vector (clade B Env, Gag, Pro, RT, Nef) Sanofi Pasteur ALVAC vCP1452 Protein subunit (clade B Env) VaxGen AIDSVAX B/B (gp120 MN, gp120 GNE8) Aluminum hydroxide gel Russell N, et al. J Acquir Immune Defic Syndr. 2007 Feb 1;44(2):203-12 HIVNET 026 (n=160) 2004 Canarypox vector (clade B Env, Gag, Pro, RT, Nef) Sanofi Pasteur ALVAC vCP1452 Protein subunit (clade B Env) VaxGen gp120 MN Aluminum hydroxide/ thimerosol Cleghorn F, et al . J Acquir Immune Defic Syndr. 2007 Oct 1;46(2):222-30. HVTN 045 (n=30) 2004 DNA plasmid (clade B Env, Gag, Pro, RT, Tat, Vpu, Rev) Emory Univ. (H. Robinson) pGA2/JS2 DNA Mulligan MJ, et al. AIDS Res Hum Retroviruses 2006;22:678-83
http://chi.ucsf.edu/vaccines Completed HVTN Trials, July 2008 (Slide 2 of 5) Protocol Number Year Completed Prime Boost Class Producer Product Name Adjuvant Class Pro-ducer Product Name Adjuvant References HIVNET 040 (n=48) 2005 VEE vector (clade C Gag) AlphaVax AVX-101 HVTN 048 (n=42) 2005 DNA plasmid (poly-epitopic: Gag, Pol, Vpr, Nef, Rev, and Env) Epimmune EP HIV-1090 Gorse G, et al. Vaccine. 2008 Jan 10;26(2):215-23. Epub 2007 Nov 20. HVTN 052 (n=180) 2005 DNA plasmids (clade B Gag-Pol-Nef; clade A,B,C Env) NIH VRC VRC-HIVDNA-009 See HVTN 057 HVTN 057 (n=70) (HVTN 052 rollover) 2006 See HVTN 052 Non-replicating adenoviral vectors (clade B Gag-Pol; clade A,B,C Env) NIH VRC VRC-ADV-014 HVTN 044 (n=70) 2006 DNA plasmids (clade B Gag-Pol-Nef; clade A,B,C Env) NIH VRC VRC-HIVDNA-009 DNA plasmid cytokine (IL2-Ig)
http://chi.ucsf.edu/vaccines Completed HVTN Trials, July 2008 (Slide 3 of 5) Protocol Number Year Completed Prime Boost Class Producer Product Name Adjuvant Class Producer Product Name Adjuvant HVTN 054 (n=48) 2006 Nonreplicating adenoviral vectors (clade B Gag-Pol; clade A,B,C Env) NIH VRC VRC-ADV-014 HVTN 056 (n=96) 2006 Peptides (polyepitopic: clade B Env, Gag, Nef) Wyeth Wyeth multiepitope CTL peptide vaccine RC-529-SE, GM-CSF HVTN 059 (n=96) 2006 VEE vector ( clade C Gag ) AlphaVax AVX-101 HVTN 042/ANRS VAC19 (n=174) 2007 Canarypox vector (clade B Env, Gag, Pro, RT, Nef) Sanofi Pasteur ALVAC vCP1452 Lipopeptides (poly-epitopic: clade B Gag, Pol, Nef) Sanofi Pasteur/ ANRS LIPO-5 HVTN 068 (n=66) 2007 Nonreplicating adenoviral vectors (clade B Gag-Pol; clade A,B,C Env) NIH VRC VRC-ADV-014 Nonreplicating adenoviral vectors (clade B Gag-Pol; clade A, B, C Env) NIH VRC VRC-HIVADV014 OR DNA plasmids (clade B Gag-Pol-Nef; clade A,B,C Env) NIH VRC VRC-HIVDNA-009
http://chi.ucsf.edu/vaccines Completed HVTN Trials, July 2008 (Slide 4 of 5) Protocol Number Year Completed Prime Boost Class Producer Product Name Adjuvant Class Producer Product Name Adjuvant HVTN 055 (n=150) 2007 MVA vectors (clade B Env, Gag; Tat, Rev, Nef, Pol) Therion TBC-M358; TBC-M335 Fowlpox vector (clade B Env, Gag; Tat, Rev, Nef, Pol) Therion TBC-F357;TBC-F349 HVTN 049 (n=96) 2007 DNA plasmids (clade B Gag, Env) Chiron Gag and Env DNA/PLG microparticles PLG Protein subunit (clade B Env) Chiron Oligomeric, V2-deleted HIV gp140 SF-162 HVTN 064 (n=120) 2008 Protein (containing T-helper epitopes from clade B Env, Gag, Pol, Vpu) + DNA plasmid (polyepitopic: Gag, Pol, Vpr, Nef) Pharmexa-Epimmune EP-1043 + EP HIV-1090 Alum (for EP-1043 only) HVTN 204 (n=480) 2008 DNA plasmids (clade B Gag, Pol, Nef; clade A,B,C Env) NIH VRC VRC-HIVDNA-016 Non-replicating adenoviral vectors (clade B Gag-Pol; clade A,B,C Env) NIH VRC VRC-ADV-014
http://chi.ucsf.edu/vaccines Completed HVTN Trials, July 2008 (Slide 5 of 5) Protocol Number Year Completed Prime Boost Class Producer Product Name Adjuvant Class Producer Product Name Adjuvant HVTN 060 (n=144) 2008 DNA plasmid (clade B Gag) Wyeth GENEVAX gag -2962 DNA plasmid cytokine (IL-12) + bupivacaine Wyeth peptides (see 056 prime)
Nonhuman Primate HIV/SIV Trials Database
Does an HIV vaccine already exist?
The answer is
Research is being conducted today to find a safe and effective vaccine !
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