Crucell Terug naar discussie overzicht

Draadje HIV/AIDS

1. flosz 17 februari 2009 19:44

   auteur info

   • flosz

     Lid sinds: 13 feb 2008

     Laatste bezoek: 01 jul 2024

   • Aanbevelingen

     Ontvangen: 5298

     Gegeven: 2795

   •    Aantal posts: 7.005

   quote:

   flosz schreef:

   Een 40-jarige Duitser, besmet met het aidsvirus, hoeft al bijna twee jaar geen medicijnen meer te slikken. Hij lijkt immuun geworden voor hiv, dankzij beenmerg van een resistente donor.
   De patiënt, deze week beschreven in het vakblad The New England Journal of Medicine, heeft in de medische wereld veel stof doen opwaaien. Zowel vanwege de aparte therapie als vanwege het opmerkelijke resultaat. De proef biedt zicht op een heel nieuwe aanpak van aids.
   Naar schatting 1 tot 3 procent van de westerlingen heeft een natuurlijke weerstand tegen hiv. Hun witte bloedcellen missen de ’deurknop’ waar het virus zich aan vastklampt om in de cellen binnen te dringen. Zonder die deurknop (het eiwit CCR5) blijft het virus buitengesloten, zodat het onverrichter zake het lichaam verlaat.
   De Duitse man was al tien jaar seropositief. Hij verorberde bergen virusremmers en voelde zich gezond. Totdat er acute leukemie bij hem werd geconstateerd. Voor hemzelf een drama, voor de wetenschap een unieke kans.
   De leukemie moest namelijk worden bestreden met een beenmergtransplantatie. En als de artsen toch een geschikte donor zochten, konden ze er net zo goed een kiezen die resistent was tegen hiv.
   Beenmerg is de bron waar alle bloedcellen uit ontstaan. Ontbreekt op het beenmerg de ’deurknop’, dan zijn automatisch ook de witte bloedcellen er vrij van. Dat bleek: toen het eigen beenmerg van de patiënt was vervangen door dat van de donor, werd hijzelf net zo resistent. In zijn bloed was weldra geen hiv-deeltje meer te zien. En zo is het nog, zelfs nu de man al twintig maanden geen virusremmer meer heeft aangeraakt.
   „Heel interessant”, zegt Ben Berkhout, hoogleraar humane retrovirologie van het AMC in Amsterdam. „Maar het is voorbarig om te zeggen dat de patiënt definitief is genezen. Waarschijnlijk zit het virus nog wel ergens, bijvoorbeeld in de hersenen of lymfklieren. Toch verwacht ik niet dat de patiënt nog symptomen krijgt, want het virus vermenigvuldigt zich niet meer.”
   Hiv-geïnfecteerden hoeven niet meteen naar het ziekenhuis te rennen voor een shot beenmerg van een resistente donor. Zulke transplantaties zijn veel te riskant. De kans op overlijden kan oplopen tot tientallen procenten. Dan toch liever pillen slikken. En los daarvan: waar zou je zoveel geschikte donoren vandaan moeten halen?
   Berkhout zoekt daarom liever alternatieven om de deurknop van de witte bloedcellen af te slopen. Nieuwe medicijnen bijvoorbeeld. Of, eleganter: gentherapie, waarbij het deurknop-gen wordt uitgeschakeld. Zijn onderzoeksgroep werkt daar hard aan.
   Op zich is het al zeker tien jaar bekend dat het virus de CCR5-ingang gebruikt om mensen te besmetten. Er bestaan zelfs medicijnen die het molecuul afplakken, zodat het virus er niet meer bij kan. Maar hiv is te slim voor die middelen: het grijpt de deurknop en het medicijn als één geheel vast. Zo komt het virus alsnog de bloedcellen binnen.
   „Gezien deze ervaring zou het beter zijn om het CCR5-molecuul helemaal te verwijderen”, zegt Berkhout. „Al komen sommige hiv-stammen niet via CCR5 binnen, maar via CXCR4. Die stammen gaan zich dan misschien sterk verspreiden. Je weet het niet. Het virus blijft ons verrassen met zijn Houdini-achtige ontsnappingroutes.”
   www.trouw.nl/nieuws/Wetenschap/articl...
   /Nieuw_beenmerg_maakt_een_patient_resistent_tegen_hiv_.html
   
   

   He he, was even zoeken…maar gevonden. (Staat ook in de krochten van IEX…krijg het helaas niet naar boven).
   
   Pest als wondermiddel tegen aids?
   Ligt onder het Catharinaplein in Eindhoven een wondermiddel tegen aids begraven? Wetenschappers denken van wel. Onder het Eindhovense plein, vlak naast een eeuwenoude kerk, ligt een schat aan bruikbaar DNA-materiaal.
   
   Het Leidse Universitair Medisch Centrum wil het DNA van deze middeleeuwse pestslachtoffers analyseren. De pest zou immers de reden zijn dat tien procent van de Europeanen vandaag de dag resistent is tegen aids.
   Kans op vernietiging
   Wetenschappers staan te springen om het DNA te bekijken, maar het moet eerst nog worden opgegraven. En de tijd dringt. De stijgende waterspiegel onder Eindhoven kan het materiaal alsnog vernietigen. Snel is begonnen met opgraven, ook al zijn de miljoenen die daarvoor nodig zijn nog niet eens geregeld. In TweeVandaag een reportage.
   www.eenvandaag.com/call.php?module=PX...
   
2. [verwijderd] 18 februari 2009 09:19

   auteur info

   • [verwijderd]

     Lid sinds: 01 jan 0001

     Laatste bezoek: 01 jan 0001

   • Aanbevelingen

     Ontvangen: 0

     Gegeven: 0

   •    Aantal posts: 0

   Another recent discovery is the role of a cell receptor called programmed cell death 1, or PD-1, in long-term survivors with HIV. Scientists think the receptor—which, when stimulated causes cells to self-destruct—is a vital component in protecting the body from diseases that cause the immune system to attack a person’s own body. It’s presence on virally infected cells, however, appears to have negative consequences, leading to a syndrome called T-cell exhaustion. In such cases the immune system can no longer adequately control the viral infection.
   
   A set of researchers who’ve been examining the characteristics of a group of people who manage to control HIV reproduction for long periods of time without ARV drugs—called elite controllers—found a characteristic in common: Their CD4 and CD8 cells tend not to have very many PD-1 receptors on their surface compared with people who do not control the virus well.
   
   Richard Jefferys, who heads up immune and vaccine research advocacy at TAG, is eager to see what will happen with a treatment that blocks PD-1. Just last year, researchers at Emory University in Atlanta found that the immune cells of monkeys infected with simian immunodeficiency virus (SIV) were far more effective when the monkeys were given an antibody that blocks PD-1. What’s more, the monkeys who got the antibody lived longer than monkeys who did not.
   
   Jefferys concedes that it’s a long way from monkeys with SIV to humans with HIV, but he’s hopeful about companies such as Medarex that are developing PD-1 antibodies for use against HIV and other diseases
   
   www.poz.com/articles/hiv_drugs_develo...
3. [verwijderd] 19 februari 2009 12:48

   auteur info

   • [verwijderd]

     Lid sinds: 01 jan 0001

     Laatste bezoek: 01 jan 0001

   • Aanbevelingen

     Ontvangen: 0

     Gegeven: 0

   •    Aantal posts: 0

   Een veelbelovend bericht voor HIV besmette mensen, het gaat over Sangamo (SGMO), een biotech uit de USA.
   Het gaat om een regelrechte gentherapy en niet om een vaccin. Dit staat in artikel uit de Newscientist, zie : www.newscientist.com/article/mg201269...
4. ved 26 februari 2009 16:07

   auteur info

   • ved

     Lid sinds: 08 aug 2001

     Laatste bezoek: 05 mrt 2025

   • Aanbevelingen

     Ontvangen: 518

     Gegeven: 4936

   •    Aantal posts: 3.041

   Hiv muteert zich langs weerstand
   Gepubliceerd: 26 februari 2009 12:37 | Gewijzigd: 26 februari 2009 12:46
   Door onze redactie wetenschap
   Rotterdam, 26 febr. Het aids-veroorzakende virus hiv verandert zo snel, dat het nu ook het afweersysteem kan overwinnen van mensen die tot nu toe genetisch redelijk beschermd waren tegen aids. De hiv-varianten die ook zonder medicijngebruik pas na jaren aids veroorzaken, zullen hierdoor verdwijnen. Een ander gevolg van de aanpassing is dat een hiv-vaccin – mocht dat er ooit komen – waarschijnlijk om de paar jaar moet worden aangepast om ‘ontsnappen’ van het virus aan de afweer te verhinderen.
   
   Dat schrijven ruim 40 onderzoekers uit 10 landen in Europa, Azië, Afrika, Amerika en Australië vandaag in een gezamenlijk artikel in het wetenschappelijke tijdschrift Nature. Zij onderzochten bij ruim 2875 met hiv-geïnfecteerde mensen de genetische kenmerken van het zogenaamde HLA-systeem. Het HLA-systeem kent zoveel genetische variatie dat iedere mens een iets anders gerichte afweer heeft. Daardoor zal er waarschijnlijk nooit een virus ontstaan waar alle mensen dood aan gaan.
   
   De deelnemende proefpersonen waren vaak al jarenlang met hiv besmet. In de opeenvolgende generaties van het virus dat in hun lichaam groeit kregen daardoor vaak mutaties de overhand die beter bestand zijn tegen de kenmerken van hun HLA-afweersysteem. De beperkte verzameling HLA-kenmerken die de weerstand tegen hiv sterk maken komen ook bij andere mensen voor. Die worden gevoeliger voor een besmetting met een ‘aangepast’ virus.
   
   Het onderzoek is gedaan in negen over de hele wereld verspreide patiëntengroepen. De onderzoekers bepaalden met genetische analyses of het virus zich aanpast aan individuele afweersystemen. Dat was vaak het geval. In Japan bijvoorbeeld komt het beschermende type HLA-B*51 veel voor. In Afrika is dat kenmerk zeldzaam. Die genetische eigenschap zorgt ervoor dat iemand vaak decennialang hiv-besmet kan zijn zonder aids te krijgen. Hiv kan echter met één specifieke mutatie ontsnappen aan HLA-B*51. Die mutatie, ontdekten de onderzoekers, zorgt er nu in Japan voor dat het beschermende effect van HLA-B*51 aan het verdwijnen is.
   
   www.nrc.nl/wetenschap/article2163835....
5. flosz 27 februari 2009 19:18

   auteur info

   • flosz

     Lid sinds: 13 feb 2008

     Laatste bezoek: 01 jul 2024

   • Aanbevelingen

     Ontvangen: 5298

     Gegeven: 2795

   •    Aantal posts: 7.005

   Via de deurmat….
   
   VAX 7 (2), February 2009
   
   Two Phase I Trials Launched
   The Indian Council of Medical Research and IAVI have launched a Phase I trial to test the safety and immune responses elicited by two AIDS vaccine candidates administered sequentially in a prime-boost regimen. The trial known as P001 will enroll 32 volunteers at clinical trial centers in Pune and Chennai to evaluate different doses and vaccination regimens of the vaccine candidates. One candidate, TBC-M4, utilizes a modified vaccinia Ankara virus vector to deliver non-infectious HIV fragments in the hope of inducing an immune response against HIV. The candidate was developed in collaboration with the National Institute of Cholera and Enteric Diseases in India and was tested previously in a Phase I trial conducted in Chennai. In this trial, administration of TBC-M4 will be preceded by a prime vaccination with ADVAX, a DNA-based vaccine candidate, which was developed at the Aaron Diamond AIDS Research Center in New York City in collaboration with Rockefeller University and IAVI. Neither of the candidates being tested in this trial can cause HIV infection.
   IAVI is also planning to begin enrolling volunteers in a Phase I trial of an adenovirus serotype 35 (Ad35)-based vaccine candidate designed and manufactured by the European biotechnology companies Crucell and Transgene. The trial will enroll 42 volunteers at the University of Rochester Medical Center who will be randomly selected to receive either two intramuscular injections of the Ad35-based vaccine candidate or placebo at three different doses. Clinicians will first administer the lowest dose and will review the safety data before proceeding to the next higher dose.
   Ad35 is a serotype or strain of the common cold virus that researchers are investigating as a vaccine vector to shuttle non-harmful fragments of HIV into the body. The prevalence of naturally circulating Ad35 is much lower worldwide than the prevalence of adenovirus serotype 5, which was the vector used in Merck’s AIDS vaccine candidate tested in the STEP trial. By using Ad35, it may be possible to circumvent issues involving pre-existing immunity to the viral vector (see VAX February 2005 Primer on Understanding Pre-existing Immunity). www.iavireport.org/vax/primers/vaxpri... —By Regina McEnery
   
   Clues from controllers
   At a symposium titled “Learning from Negative Trials,” Emory University researcher Eric Hunter said the STEP trial—the recently conducted Phase IIb trial of Merck’s adenovirus serotype-5 based vaccine candidate that showed the candidate offered no protection against HIV—has provided an opportunity to explore the basis for this lack of protection, which could help inform the design of future vaccine candidates.
   Researchers are also carefully analyzing long-term nonprogressors (LTNPs) and more specifically elite controllers—individuals who can control HIV infection so that it is undetectable by standard tests for an extended period of time without ARV therapy—to mine for clues that may indicate the types of immune responses a vaccine candidate should induce. David Heckerman, a researcher at Microsoft, in collaboration with Bruce Walker, director of the newly formed Ragon Institute and Harvard AIDS researcher Florencia Pereyra, analyzed a group of LTNPs and mapped the specific regions on HIV that were targeted by their cellular immune responses.
   They then analyzed a sub-group of vaccinated volunteers from the STEP trial who became HIV infected, despite vaccination, from natural exposure to the virus, to see if individuals with immune responses that targeted these same regions of the virus were better able to control HIV infection. Heckerman reported that this was indeed what they found. When the immune responses in STEP trial volunteers targeted one of what Heckerman identified as the six critical regions on the virus, it correlated with their having lower levels of HIV in their blood.
   This suggests that these bulls-eye regions on the virus may be important for generating an immune response that could control HIV infection and could be used in the design of future AIDS vaccine candidates.
   Several other studies were also presented on the unique characteristics that lead to control of HIV infection. Mark Connors, chief of the HIV-Specific Immunity Section at the US National Institutes of Allergy and Infectious Diseases said, in his estimation, it is likely that there will be evidence from clinical trials in the near future showing that candidate vaccines can induce similar T-cell responses to those seen in elite controllers. —By Kristen Jill Kresge and Regina McEnery
   
   www.iavireport.org/Vax/English/ECurre...
   
6. flosz 1 maart 2009 15:24

   auteur info

   • flosz

     Lid sinds: 13 feb 2008

     Laatste bezoek: 01 jul 2024

   • Aanbevelingen

     Ontvangen: 5298

     Gegeven: 2795

   •    Aantal posts: 7.005

   How HIV stays one step ahead of immune system
   Researchers seeking a vaccine find that the virus that causes AIDS quickly evolves into different strains to battle different populations' genetic makeups.
   By Mary Engel
   February 28, 2009
   HIV, the virus that causes AIDS, is one of the fastest-evolving entities known. That's why no one has yet been able to come up with a vaccine: The virus mutates so rapidly that what works today in one person may not work tomorrow or in others.
   
   A study published Wednesday in the journal Nature confirms that dizzying pace of evolution on a global scale
   "It's very clear there's a battle going on between humans and this virus, and the virus is evolving to become unrecognized by the immune system," said Dr. Bruce Walker, one of the researchers and director of the Ragon Institute, at Massachusetts General Hospital in Boston. "It does make clear what a huge challenge making a vaccine is."
   
   HIV evolves to escape the immune system, much in the same way that bacteria mutate under pressure by antibiotics, Walker said.
   
   Researchers looked at HIV genetic sequences in the United Kingdom, South Africa, Botswana, Australia, Canada and Japan to see how they evolved in response to a key set of molecules in the human immune system, called human leukocyte antigens. These molecules direct the immune system to recognize and kill HIV and other infectious diseases.
   Genes that encode human leukocyte antigens vary among humans, and even small differences can dramatically affect a person's response to HIV infection. For example, an adult infected with HIV will survive on average about 10 years without anti-HIV drugs before developing acquired immune deficiency syndrome. But some people will progress to AIDS within a year, and others can survive without treatment for 20 years.
   
   The study published online Wednesday found that mutations occurred not just in individuals but on a population level. That is, if a particular genetic immune sequence was common in a population, the HIV mutation that evolved to escape it became the most common strain of HIV, even in those without that particular human leukocyte antigen gene.
   
   "What this study does is give an explanation for why there are different HIV strains in different parts of the world," Walker said. "The genetic makeup of people in different regions is influencing the virus in specific ways."
   
   This would appear to be bad news for the director of the newly opened Ragon Institute of MGH, MIT and Harvard, which was founded to develop vaccines for HIV and other infectious diseases.
   
   But Walker saw the results as hopeful. He said that mutations can actually make the virus less fit -- that is, unable to replicate as quickly or do as much damage. His challenge is to find what kind of pressure results in this kind of mutation.
   
   Researchers from the Ragon Institute, Oxford University in England, Kumamoto University in Japan, and Royal Perth Hospital and Murdoch University in Australia analyzed the genetic sequences of HIV and human leukocyte antigen genes in 2,800 people total.
   www.latimes.com/news/nationworld/nati...,0,7364282.story
   news.bbc.co.uk/1/hi/health/7907774.stm
   ******************************
   
   Bruce Walker--> Crucell/Beth Israel Deaconess Medical Center T cell-based HIV vaccine.
   
   "This is an extremely important study because it shows that there is still hope for vaccines currently in the pipeline," says Bruce Walker, MD, Director of the Harvard University Center for AIDS Research (CFAR). "It also gives the first clear indication of the level and type of immunity that will likely be needed for an AIDS vaccine to work."
   www.bidmc.org/News/InResearch/2008/No...
   
   
7. flosz 24 maart 2009 23:39

   auteur info

   • flosz

     Lid sinds: 13 feb 2008

     Laatste bezoek: 01 jul 2024

   • Aanbevelingen

     Ontvangen: 5298

     Gegeven: 2795

   •    Aantal posts: 7.005

   How HIV interacts with the immune system
   
   Humans are repeatedly exposed to various disease-causing organisms known
   as pathogens, including viruses and bacteria, which pose a threat to their health. The body
   defends itself against these foreign invaders using an incredibly complex network of cells,
   molecules, tissues, and organs, which together make up the immune system.
   There are two categories of defenses the immune system uses to combat pathogens:
   innate and adaptive. The innate immune responses are the first responders against an
   invading virus, acting within hours. These responses are not specific, so whether the
   pathogen is a cold virus or HIV, the response will be very similar. Innate immune responses
   don’t always clear an infection. Instead they help control the virus until the adaptive
   immune responses are ready to kick in. The adaptive immune responses take days to
   weeks to activate, partly because they are produced in response to a specific pathogen.
   Adaptive responses are further divided into two types: cellular and antibody responses.
   The adaptive immune responses are orchestrated by two main classes of cells: B cells,
   which produce antibodies, and T cells, which conduct cellular immune responses. B and T
   cells are generated in the bone marrow and thymus (shown in red) and from there migrate
   throughout the body. They mature in the lymph nodes, spleen, and the mucosal tissues that
   line the intestine, nasal, respiratory, and genital tracts. B and T cells travel between tissues
   and organs using a network of vessels known as the lymphatic system. Lymph nodes occur
   where lymphatic vessels converge and are the communication hubs where different cells
   of the immune system meet and greet.
   www.iavireport.org/specials/Immune_La...
   
8. flosz 27 maart 2009 10:54

   auteur info

   • flosz

     Lid sinds: 13 feb 2008

     Laatste bezoek: 01 jul 2024

   • Aanbevelingen

     Ontvangen: 5298

     Gegeven: 2795

   •    Aantal posts: 7.005

   The Lancet, Early Online Publication, 20 March 2009
   doi:10.1016/S0140-6736(09)60321-4 Cite or Link Using DOI
   AIDS: lessons learnt and myths dispelled
   Prof Peter Piot MD a b, Prof Michel Kazatchkine MD c , Mark Dybul MD e, Julian Lob-Levyt MB d
   
   Nearly 30 years into the AIDS epidemic, we are able to assess our progress in tackling the disease with both increased knowledge and the benefit of hindsight. This Viewpoint examines what we—the international community—got right, what we got wrong, and why we need to urgently dispel several emerging myths about the epidemic and the global response to it.
   When HIV was emerging in the early 1980s, we clearly underestimated the global effect that the disease would have, and that in only a few decades, tens of millions of people worldwide would become infected. The epidemic nowadays is the result of what 30 years ago was an unpredictable—but tremendously potent—combination of intimate personal behaviours (notably, unprotected sex and needle sharing) and socioeconomic factors (including poverty, gender inequity, social exclusion, and migration) that have affected nearly every country worldwide.
   We also underestimated the extent to which stigma and discrimination—against people living with HIV and those most vulnerable to it—would remain formidable obstacles to tackling AIDS. Although the introduction of antiretroviral treatment in developed countries 12 years ago and its dissemination to developing countries in recent years has largely changed the perception that AIDS is a so-called death sentence, people living with HIV/AIDS in many countries continue to experience ostracism, violence, eviction, loss of employment, and restrictions on their ability to travel. Stigma and fear of discrimination still prevent many people from accessing crucial prevention and treatment services, including HIV testing. Roughly 60 countries worldwide continue to deny or restrict entry to people living with HIV/AIDS, showing how differently HIV infection is perceived and treated compared with other diseases.
   Notwithstanding these challenges, we can also say that, after years of inadequate action, we underestimated the sense of urgency and solidarity that would eventually develop in the global AIDS movement, leading to an unusual convergence of political will, money, and science. Since the UN General Assembly Special Session on AIDS in 2001, the international community has substantially increased resources available for AIDS by creating the Global Fund to Fight AIDS, Tuberculosis and Malaria. The USA has launched the US President's Emergency Plan for AIDS Relief (PEPFAR). As a result, more than 3 million people have now gained access to antiretroviral treatment, which was unimaginable only 5 years ago. People living with and affected by HIV, non-governmental organisations, civil society groups, and the private sector are more engaged in the response than ever before. However, in an unstable global political and economic environment, we will all have to work even harder than previously to ensure that this momentum is expanded and sustained.1
   Some aspects of HIV/AIDS were also overestimated in the early years of the epidemic—notably, the pace with which HIV would spread in regions other than sub-Saharan Africa. For example, in the early 1990s, many were concerned that, left unchecked, HIV in Asia would spread quickly outside concentrated epidemics of sex workers, men who have sex with men, and injecting drug users, and that the disease would take on the proportions of the devastating generalised epidemics occurring in southern Africa.
   Fortunately, this scenario has not yet happened, other than in Papua New Guinea, which now has a serious AIDS epidemic. Nevertheless, the Asian epidemic is showing its own worrying trends. A growing proportion of people with HIV in the region are women—notably married women. In Vietnam, women now account for a third of people infected.2 At the same time, HIV prevalence in men who have sex with men is growing across Asia—eg, the proportion of men who have sex with men in Bangkok who are living with HIV increased from 17% to 28% between 2003 and 2005.3 Because the continent of Asia has a very large population—more than 2•5 million people are living with HIV/AIDS in India alone—it will continue to demand substantial resources and intensive efforts to improve HIV prevention strategies and provide treatment to people who need it.
   Meanwhile, our ability to estimate the number of people living with HIV/AIDS has become increasingly advanced. Estimates from UNAIDS/WHO are based on all relevant data available, including surveys of pregnant women attending antenatal clinics, population-based surveys, sentinel surveillance in populations at increased risk of HIV infection, case reporting, and registration systems. Different combinations of these approaches, and the consensus reached by leading experts nationally and internationally, are producing both improved data from country surveillance and steady advances in modelling methods. The overall result is increasingly accurate estimates.
   Despite the remarkable innovations and successes of antiretroviral treatment, we have also overestimated our capacity to devise technological solutions to prevent HIV. Notwithstanding the optimistic projections of the US Health and Human Services Secretary Margaret Heckler in 1984, that an AIDS vaccine would be ready for testing in about 2 years, we still seem many years away from either a vaccine or a microbicide to protect against HIV transmission, especially after a recent series of disappointing trial results.4, 5 Nevertheless, much has been learned about how HIV enters and acts within the body, and continued investments in new prevention technology remain a crucial part of the AIDS research agenda. Encouragingly, in the past 2 years, studies have shown that male circumcision reduces HIV infection in men by up to 60%,6 although it does not reduce transmission from men to women or between men.
   One of the most common myths is that HIV prevention is not working. However, much evidence suggests that, in several countries, prevention programmes are effective. Between 2005 and 2007, coverage of services to prevent mother-to-child transmission of HIV increased from 14% to 33%.7 As a result, in 2007, we noted for the first time a substantial decrease in the number of children born with HIV.
   Prevention is, of course, about not only technology, but also behaviour. In many countries on several continents, changes in sexual behaviour (such as waiting longer to become sexually active, having fewer partners, and increased condom use) have been followed by reductions in the number of new HIV infections, providing evidence that efforts to change behaviour can and do work.8
   However, sustaining behaviour change in the long term remains a major challenge. For example, the number of new HIV diagnoses in men who have sex with men doubled in Germany between 2002 and 2006, and increased by more than three-quarters in Switzerland.2 These data could be attributable to complacency about AIDS and the sense that a treatable disease is somehow less threatening than are other diseases, and to a decrease in HIV prevention efforts in western Europe. Some developing countries that have previously had much success with HIV prevention, such as Uganda, have also had increases in rates of HIV transmission.2
   
9. flosz 27 maart 2009 10:55

   auteur info

   • flosz

     Lid sinds: 13 feb 2008

     Laatste bezoek: 01 jul 2024

   • Aanbevelingen

     Ontvangen: 5298

     Gegeven: 2795

   •    Aantal posts: 7.005

   Another major challenge is that, nearly 30 years into the epidemic, only about half of countries have national HIV prevention targets, whereas nearly 90% have targets for AIDS treatment. Furthermore, when prevention programmes do exist, they are often under-resourced and do not have the quality and scale that are needed to have a real effect in communities. They need to be better targeted to where the epidemic is, both in terms of populations at risk and geographic areas. Much has been published about the need for precise targeting of HIV prevention, especially in concentrated epidemics. But even saturation coverage of vulnerable groups will have little lasting effect without concerted and concrete efforts to change social standards and tackle social factors of the epidemic, such as homophobia and the low status of women in many societies. Programmes also need to be designed and managed more efficiently, including increased use of skills and practices from the business sector.9, 10
   An increasingly recurrent myth is that one solution, or a so-called silver bullet, will comprehensively prevent HIV transmission. Elimination of concurrent partnerships, circumcision of all men, focusing of prevention efforts on sex workers, universal HIV testing, and provision of antiretroviral therapy as soon as possible after infection, have all received attention as potential solutions for prevention of HIV transmission. Scaling up strategies for harm reduction, such as methadone substitution and the provision of clean needles for injecting drug users, remains neglected in many countries in which injection drug use is a major means of HIV transmission. Although these strategies are all important, no approach will be enough on its own, and the promotion of one solution is, in our view, irresponsible. If we have learned one lesson in the past 27 years, it is that effective HIV prevention depends on customising the right mix of interventions for every context and ensuring the necessary coverage of them.8 If we are to successfully increase access to HIV prevention, we have to be prepared to come to terms with complexity, effectively use all the methods that are available, include affected communities, engage relevant business expertise, and foster leadership to help change harmful social norms.
   Another prevailing misconception is that heterosexual transmission of HIV is uncommon outside Africa. Generalised epidemics are occurring in Haiti and Papua New Guinea, whereas heterosexual transmission drives the epidemic between sex workers, their partners, clients, and clients' partners in Asia and elsewhere. HIV infections in women are rising worldwide. The main method of transmission in Thailand is no longer between sex workers and their clients or between injecting drug users: it is between married couples.3 Furthermore, AIDS remains the leading cause of death in African-American women in the USA.11 To characterise all African epidemics as exclusively heterosexual is also incorrect. Methods of transmission and affected groups are many and varied. In Kenya, for example, HIV infections in men who have sex with men and injecting drug users are an increasing cause for concern.12
   Although such observations neither indicate nor predict extensive or generalised HIV epidemic spread, they do draw attention to the fact that heterosexual transmission of HIV occurs in a wide range of settings. They also show that the HIV epidemic is constantly evolving, and continually surprising.
   As we approach the fourth decade of the AIDS epidemic, new global challenges are competing for the attention of political leaders and donors at the same time as they face the present financial crisis. Alarmingly, a myth has begun to emerge that too much money is spent on AIDS. But AIDS remains the leading cause of death in Africa and the sixth highest cause of mortality worldwide.13 It is fitting that investment in fighting AIDS has finally begun to increase substantially, rising from a paltry US$250 million in 1996 to around $14 billion in 2008.14 Even so, UNAIDS estimates that available resources at present fall well short of what will be needed to reach coverage targets for 2010.14 Moreover, mobilisation around AIDS has increased available resources for tuberculosis and malaria (largely through the Global Fund) to unprecedented amounts and generally contributed to an increase in global funding for health.
   Increased resources are beginning to have an effect, as are antiretroviral treatment programmes, which have been established in developing countries for less than 5 years. Among the first was in Malawi, which recorded a 44% reduction in mortality in workers at the national electricity company—one of the country's largest employers—after the roll-out of antiretroviral treatment.15 In Botswana, where HIV prevalence has reached 30%, mortality has begun to fall in the age groups most affected by AIDS since the introduction of antiretroviral treatment.16
   Another major myth that needs to be dispelled is that investments in AIDS are being made at the expense of health systems that are chronically underfunded. Although AIDS has exposed weaknesses in health systems, funds for this disease are making a major contribution to the strengthening of health systems.
   The Global Fund and PEPFAR are now among the biggest investors in health systems, joining other funders such as the GAVI Alliance. Although drugs and other commodities account for nearly half of Global Fund spending (figure 1), 35% of the Fund's financing for AIDS, tuberculosis, and malaria contributes directly to supporting human resources, infrastructure and equipment, and monitoring and evaluation: all key components of health systems. Overall, the Fund has committed more than $4 billion in these three areas. From 2004 to 2009, on the basis of conservative estimates, PEPFAR will commit more than $4 billion to health systems, including more than $1 billion in 2009 alone (figure 2).
   The results of these investments are clearly noticeable on the ground, where AIDS resources are contributing to the refurbishment of health centres, the hiring of new health workers, and the establishment of local schemes for national health insurance. In Ethiopia, resources from the Global Fund and PEPFAR are strengthening the health system and enabling the rapid scale-up of diagnostic and treatment services for AIDS and tuberculosis.
   AIDS programmes have other benefits for health systems. In many African countries, AIDS services and treatment keep health workers alive, healthy, and able to work. A study in Rwanda,17 for example, showed that within 2 months of starting to provide antiretroviral treatment in PEPFAR-supported sites, the average number of new admissions at seven sites dropped by 21%, freeing up health workers and enabling valuable resources to be dedicated to other health-care needs. AIDS resources have greatly strengthened overall laboratory capacity and systems for distribution of drugs. In Nicaragua, new equipment financed by the Global Fund for the National Reference Laboratory enables not only processing of HIV tests, but also processing and storage of blood samples taken for other purposes.
   
10. flosz 27 maart 2009 10:56

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    A further myth that has emerged suggests that strengthening health services alone will solve the world's health problems, including AIDS. Improvements to health infrastructure and measures to tackle the human resources crisis for health are long overdue in many countries and deserve much support, especially since they will be essential for the further roll-out of antiretroviral treatment. At the same time, what might have happened to the 4 million people on antiretroviral therapy in developing countries if we had waited until health services had been strengthened before launching HIV treatment programmes is a sobering thought.
    Improved health systems alone are not enough to end the AIDS epidemic. We have known since the early 1990s that, although the health sector has a major role in provision of HIV treatment, it cannot and does not meet the full range of needs. Whereas well functioning health and community services will be key to provision of antiretroviral therapy for decades to come—as well as services for the prevention of mother-to-child HIV transmission, blood safety, and male circumcision—most other HIV prevention activities are happening largely outside the health sector. This tenet is especially true in the case of programmes that reach populations at high risk and at the margins of society, youth, and injecting drug users, and programmes promoting social change.
    AIDS funding is often used to lend support to the establishment of quality sex-education programmes in schools, efforts to eliminate violence against women, and care for orphans. The benefits of such activities extend far beyond an effective AIDS response.
    A last myth is that AIDS has somehow been solved. However, we have only just begun to see a return on the investments of the past decade in the form of falling rates and fewer deaths, indicating a new phase in the AIDS response; it by no means suggests that the problem is anywhere near solved. This new phase is characterised by a new set of challenges that could well prove more difficult than any that we have encountered so far.
    We need to recognise that AIDS is a long-term event. Tackling it is complex, but our successes so far indicate what is possible. In the future, we should pay far greater attention to epidemiological trends and to the social factors driving them. We have to identify now how to finance a sustained response to AIDS for another several decades, and develop longlasting links with broader efforts to strengthen health systems and health workforces as well as other development efforts, such as in education and food security. At the same time we have to continue to invest in research and development to produce improved diagnostic tests and less toxic and more effective drugs, in addition to microbicides and vaccines. A serious and concerted effort is also needed to tackle stigma and discrimination, ensuring that people most at risk actually receive the services that they need. Only when we have met all these aims will we be anywhere close to the point at which we can truthfully say that the fight against AIDS is being won.
    www.thelancet.com/journals/lancet/art...
    
12. flosz 31 maart 2009 12:05

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    Onderzoeksechtpaar vindt hiv-achilleshiel
    
    zondag, 29 maart 2009
    De aids-onderzoekers van de Ruthgers Universiteit in New Jersey, het onderzoeksechtpaar Gail Ferstandig Arnold en Eddy Arnold, hebben een belangrijke stap gezet in hun onderzoek naar een vaccin tegen hiv, zo blijkt uit een publicatie in het Journal of Virology, van 11 maart j.l.
    De Arnolds en hun team zijn er (met steun van de National Institutes of Health) in geslaagd om een stukje van het hiv-virus te selecteren dat het virus helpt om de cel binnen te komen. Dit deeltje hebben ze op het oppervlak van een doorsnee verkoudheidsvirus gezet en daarna hebben ze er dieren mee gevaccineerd. Ze ontdekten dat de dieren antilichamen maakten die beschermden tegen een ongebruikelijk grote hoeveelheid hiv-isolaten of varianten.
    
    Muteren
    Onderzoekers zijn er eerder al in geslaagd om effectieve antilichamen op te wekken, maar meestal slechts tegen een zeer beperkt aantal hiv-typen. Hiv heeft sterk de neiging om te gaan muteren en dan zullen antilichamen die zijn ontwikkeld tegen slechts één type waarschijnlijk niet in staat zijn om de strijd tegen gemuteerde varianten aan te gaan. De geografische variëteiten met verschillende mutaties vormen een van de grootste uitdagingen in de zoektocht naar een breedspectrum vaccin dat beschermt tegen de enorme reeks hiv-variëteiten.
    De aanpak van het team van de Arnolds is om een deel van het aids-virus te nemen dat cruciaal is voor het virus om zijn levenscyclus te voltooien, en dan deze achilleshiel als doel te nemen. 'Het deeltje waar we ons op richtten, speelt een rol in het vermogen van hiv om de cel binnen te komen, en komt bij de meeste hiv-variëteiten voor. Het is een mechanisme dat voor het virus niet zo makkelijk opnieuw te verzinnen is en dus een perfect doel.
    
    Rocky Mountains verplaatsen
    Terwijl de meeste vaccins gemaakt worden van de eigenlijke ziekteverwekker, die verzwakt of onschadelijk gemaakt is, om de productie van antilichamen te stimuleren, is hiv simpelweg te gevaarlijk om als basis voor een vaccin te dienen. Wat de Arnolds hebben gedaan, is een relatief onschuldig verkoudheidsvirus (rhinovirus) nemen en daarin het bewuste hiv-onderdeel in te bouwen. Dit moet zo gedaan worden dat het hiv-onderdeel zijn vorm behoudt, zodat het immuunsysteem het ziet en een afweerreactie opwekt alsof het om het echte hiv gaat.
    Dat klinkt makkelijk, maar het is geen sinecure om dit daadwerkelijk voor elkaar te krijgen. Het hiv-onderdeel moet uit zijn oorspronkelijke omgeving genomen worden en op het rhinovirus geplaatst worden alsof het daar hoort. Eddy Arnold vergelijkt dit met het oppakken van de Rocky Mountains en ze in India neerzetten alsof ze daar precies altijd zo hebben gestaan.
    
    Net loterij
    Door het gebruik van recombinant-technologie (het verplaatsen van erfelijk materiaal) ontwikkelden het onderzoeksteam een methode om systematisch miljoenen hiv-variaties te testen met het rhinovirus en zo een bibliotheek aan hiv-variaties (een zogenoemde 'combinatoriële library') op te bouwen. 'Het is net een loterij: hoe meer loten je koopt, hoe meer kans je hebt om te winnen', aldus Eddy Arnold. 'Het echte opwindende eraan is, dat we virussen vonden die antilichamen konden opwekken tegen ongelooflijk veel variëteiten van hiv-isolaten.'
    'We moeten wel voorzichtig zijn met uitspraken en niet te veel overdrijven', aldus Eddy Arnold, 'want de sterkte van de respons is niet gigantisch, maar wel significant. Dit is de eerste keer dat deze achilleshiel is blootgelegd. De immuunrespons is waarschijnlijk niet sterk genoeg voor een vaccin, maar we hebben wel laten zien dat het principe werkt.'
    
    www.nvi-vaccin.nl/?id=62&bid=1051
    
13. voda 16 april 2009 16:20

    auteur info

    • voda

      Lid sinds: 02 dec 2005

      Laatste bezoek: 05 mrt 2025

    • Aanbevelingen

      Ontvangen: 93442

      Gegeven: 22909

    •    Aantal posts: 384.388

    Glaxo en Pfizer samen in strijd tegen aids
    16 april 2009, 12:58 | ANP
    LONDEN (ANP) - De farmagiganten GlaxoSmithKline en Pfizer bundelen hun krachten in de ontwikkeling van medicijnen tegen aids en het HIV-virus dat de ziekte kan veroorzaken.
    
    Het daarvoor nieuw op te richten bedrijf komt voor 85 procent in handen van het Britse Glaxo, het Amerikaanse Pfizer krijgt de resterende 15 procent. Dat hebben de bedrijven donderdag bekendgemaakt.
    
    Het HIV-virus kan pas jaren na besmetting het afweersysteem aantasten waarna de besmette persoon aids krijgt. Met de te ontwikkelen medicijnen hopen Glaxo en Pfizer het HIV-virus zodanig te bestrijden dat het niet uitmondt in aids.
    
    Elf producten
    
    Het nieuwe bedrijf zal volgens Glaxo en Pfizer bijna een vijfde van de markt voor aidsmedicijnen in handen hebben met in eerste instantie elf producten. De bedrijven verwachten met de bestaande portefeuille een omzet van 1,6 miljard pond sterling te halen, gebaseerd op de resultaten van vorig jaar.
    
    Naast de bestaande producten zitten er zes medicijnen in de ontwikkelingsfase, waarvan vier in een vergevorderd stadium. Dominique Limet, afkomstig van Glaxo, is de beoogde bestuursvoorzitter van het nieuwe bedrijf.
    
    Vanwege de benodigde investeringen in het op te richten bedrijf, waarvan de omvang niet bekendgemaakt is, verwacht Glaxo volgend jaar 1 a 2 procent minder winst per aandeel, gevolgd door nog eens 1 procent in 2011. Pfizer verwacht een geringe bijdrage in die jaren omdat het een kleinere investering doet. De oprichting wordt naar verwachting aan het eind van dit jaar voltooid.
    
    
14. flosz 1 mei 2009 19:13

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    Van de deurmat:
    Wow imo.
    Researchers Catch HIV on Film
    Using high-speed three-dimensional imaging equipment and a version of HIV embedded with a green fluorescent protein, a team of virologists and physicists were recently able to track and film in real-time the process by which an HIV-infected cell passes the virus to other cells. The movie tracked one of HIV’s proteins, known as Gag, as HIV was transmitted from an already infected CD4+ T cell to another CD4+ T cell that it was targeting www.youtube.com/GreenVSLab
    In Day-Glo colors, these movies illustrate what happens when HIV-infected cells collide with uninfected cells and convey how rapidly the Gag proteins—with the help of adhesive contacts called virological synapses that are formed at the juncture of CD4+ T cells—pass from infected cell to uninfected cell.
    Together, virologists at Mount Sinai School of Medicine in New York City, who created the fluorescent version of HIV, and physicists at the University of California-Davis, who supplied the expertise in high-speed imaging, produced 12 movies detailing this process. Some depict just a few seconds in the life cycle of the virus, while others—with the help of time-lapsed photography—span several days. Although these short films may not compete with Hollywood blockbusters, after a week on YouTube, one of the short films had more than 150,000 hits.
    Benjamin Chen, the Mount Sinai virologist who created the glowing HIV, says a fast video microscope capable of taking three-dimensional images of infected cells every second or so, showed that HIV Gag quickly congregates at the virological synapse, forming a button shape. The footage then shows the viral proteins being ushered into a target cell’s endosome, a membrane-bound compartment that many other viruses use to gain entry into cells but which HIV was not thought to favor much.
    Chen says the footage depicting cell-to-cell transfer of HIV could provide valuable insights into new strategies for AIDS vaccine and drug development. —By Regina McEnery
    www.iavireport.org/vax/VAXApril2009.asp
    
    www.sciencemag.org/cgi/content/abstra...
    
15. flosz 15 mei 2009 18:59

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    DNA prime doesn’t pay
    Dan Barouch, an associate professor of medi¬cine at Beth Israel Deaconess Medical Center and Harvard Medical School, also reported results from a study in macaques testing a prime-boost regimen of DNA/Ad5 vaccines. Barouch’s adeno¬virus vaccine, referred to as Ad5HVR48, is com¬posed almost entirely (~98%) of Ad5, except for the hexon protein, which is swapped with the same protein from the less common Ad48 serotype.
    Pag. 5.
    
    Building a better antigen
    Barouch also presented results from a mosaic vaccine study in rhesus macaques designed to achieve optimal coverage of various 9mers of a given protein. In theory, he said, a mosaic vaccine with sequences encoding a given number of mosaic antigens will have better breadth and coverage than a vaccine candidate encoding the same num-ber of consensus antigen sequences or one encod-ing the same number of naturally occurring anti-gen sequences (Nat. Med. 13, 100, 2007). In this study, Barouch used an Ad26 vector with sequences encoding two mosaic antigens for each of the three HIV proteins Gag, Pol, and Env, designed to optimize coverage of the global HIV-1 M group, which represents the vast major-ity of all global HIV sequences. Macaques were immunized intramuscularly with the mosaic vac-cine candidate; an Ad26 vector with one set of consensus antigen sequences for Gag, Pol, and Env; or an Ad26 vector with one set of natural sequences for these proteins that had the broadest 9mer coverage of all clade C HIV sequences in the Los Alamos National Laboratory HIV sequence database.
    Pag.6
    
    STEP by step
    Susan Buchbinder, principal investigator of the STEP trial, provided another update on this now notorious Phase IIb trial of Merck’s Ad5-based vaccine candidate, MRKAd5. Receipt of MRKAd5 was associated with enhanced suscep¬tibility to HIV infection, most significantly among uncircumcised MSM, who had pre-existing immunity to the Ad5 vector. An explanation for these findings has so far been elusive.
    Pag. 7.
    
    www.iavi.org/Lists/IAVIPublications/A...
    
16. flosz 19 mei 2009 10:35

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    SA researchers develop Aids vaccine
    May 19 2009 at 07:18AM
    By Nontobeko Mtshali
    
    South African researchers have made history by developing an Aids vaccine that was clinically tested in the US for local use.
    
    Professor Glenda Gray, of the Perinatal HIV Research Unit, on Monday said that unlike in the past, when developed countries produced vaccines and had them tested in developing countries, South Africa could now boast its very own vaccine.
    
    Gray was speaking at the Banner of Truth Ministries Church in Devland, Joburg, as part of World Aids Vaccine Day celebrations.
    
    Gray said that if the vaccine was a success it would be available to the public for free because the research was government funded.
    She explained that 12 Americans were nearing the end of the first phase of the vaccine's clinical trial, and the rollout would start in South Africa within the next three weeks.
    
    "Without a vaccine, we won't be able to eradicate the disease. We try and we fail, but one day we're going to win," said Gray.
    
    "We know that this virus is clever; we have to up our game. Just when we think we have it, it changes its form," she said.
    
    Despite having tried to create a successful vaccine for 20 years, Gray said "some scientists believe we're almost there".
    
    Community Advisory Board (CAB) chairwoman Gloria Malind said a vaccine was the only hope of beating the Aids pandemic. The CAB works with HIV/Aids researchers and protects the rights of volunteers who take part in trials.
    
    "We came here to see if one day we'll get a vaccine that will be safe and efficient. Our hope is that we can lessen the number of people who are ill and those who are dying," she said.
    
    Already the vaccine rollout has 18 confirmed participants in Soweto and another 18 in Cape Town, while 60 more are awaiting confirmation if they are eligible to go ahead with the rollout.
    
    Gray said that for a person to be eligible to take part in a vaccine clinical trial, they had to be over 18 years of age and healthy.
    
    "You have to be HIV-negative and in good health; we want people to be low-risk," she said.
    
    Gray explained that no one takes part in the trial without being fully informed of what it entails.
    
    She said common side-effects that participants experience included flu-like symptoms, nausea, stomach ache and dizziness.
    
    "We never do trials if the benefits don't outweigh the risks," she said, adding that they had to go through stringent scrutiny before testing the vaccines on people.
    
    Fikile Mkhatshwa, 37, volunteered to take part in a vaccine clinical trial in 2003. She said people are misinformed about these trial runs and stigmatise the volunteers, thinking they are HIV-positive.
    
    "In order for you to understand, you must seek information and know what vaccination is. I would be happy to see the community conquering this," she said. My goal was not to do this for me, but for my kids and the next generations."
    www.iol.co.za/index.php?set_id=1&clic...
    
    Saavi 102/HVTN 073
    Saavi MVA-C and Saavi DNA-C2
    
    Trials of Preventive HIV/AIDS Vaccines Worldwide
    avac.org/trials_table.htm
    
17. flosz 29 mei 2009 20:53

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    IAVI currently supports three clinical trials of candidate AIDS vaccines.
    
    Ad35-GRIN/ENV A—An Ad35-based AIDS vaccine candidate (USA): This Phase I trial, launched in collaboration with the University of Rochester Medical Center, aims to evaluate the safety and immunogenicity of an AIDS vaccine candidate based on serotype 35 of the adenovirus (Ad35).
    
    Key facts:
    • The vaccine candidate will be tested in approximately 42 adult, HIV-uninfected, healthy, low-risk volunteers in a randomized, placebo-controlled, double-blind study. Volunteers will receive either the candidate vaccine or the placebo intramuscularly at months 0 and 6. The vaccine candidate will be given at three dosage levels: 2 billion, 20 billion and 200 billion virus particles. Clinicians will initially enroll volunteers for the lowest dosage and will only advance to the higher dosage after careful review of the safety data collected from the first group
    
    • The vector was designed and assessed in preclinical studies by IAVI. It incorporates into the Ad35 genome portions of several synthetic genes for proteins from clade A of HIV-1, the predominant type of HIV circulating in East Africa
    
    • The underlying technology for the Ad35 vector was licensed from Crucell, NV, a Dutch biotech company, and the vaccine candidate was manufactured by Transgene, SA, a French biotech
    
    www.iavi.org/research-development/tri...
    
    VAX, Vol. 7 (5), May 2009
    Published: May 2009
    www.iavi.org/Lists/IAVIPublications/a...
    
18. flosz 16 juni 2009 01:53

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    Journal of Virology, July 2009, p. 6508-6521, Vol. 83, No. 13
    Nancy A. Wilson,1* Brandon F. Keele,3 Jason S. Reed,1 Shari M. Piaskowski,1 Caitlin E. MacNair,1 Andrew J. Bett,5 Xiaoping Liang,5 Fubao Wang,5 Elizabeth Thoryk,5 Gwendolyn J. Heidecker,5 Michael P. Citron,5 Lingyi Huang,5 Jing Lin,5 Salvatore Vitelli,5 Chanook D. Ahn,1 Masahiko Kaizu,1 Nicholas J. Maness,1 Matthew R. Reynolds,1 Thomas C. Friedrich,1,2 John T. Loffredo,1 Eva G. Rakasz,1 Stephen Erickson,4 David B. Allison,4 Michael Piatak Jr.,6 Jeffrey D. Lifson,6 John W. Shiver,5 Danilo R. Casimiro,5 George M. Shaw,3 Beatrice H. Hahn,3 and David I. Watkins1
    Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin,1 Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin,2 Departments of Medicine and Microbiology, University of Alabama at Birmingham, Birmingham, Alabama,3 Section on Statistical Genetics, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama,4 Merck Research Labs, West Point, Pennsylvania,5 SAIC Frederick, Inc., NCI-Frederick, Frederick, Maryland6
    Received 6 February 2009/ Accepted 22 April 2009
    
    Vaccine-Induced Cellular Responses Control Simian Immunodeficiency Virus Replication after Heterologous Challenge
    
    All human immunodeficiency virus (HIV) vaccine efficacy trials to date have ended in failure. Structural features of the Env glycoprotein and its enormous variability have frustrated efforts to induce broadly reactive neutralizing antibodies. To explore the extent to which vaccine-induced cellular immune responses, in the absence of neutralizing antibodies, can control replication of a heterologous, mucosal viral challenge, we vaccinated eight macaques with a DNA/Ad5 regimen expressing all of the proteins of SIVmac239 except Env. Vaccinees mounted high-frequency T-cell responses against 11 to 34 epitopes. We challenged the vaccinees and eight naïve animals with the heterologous biological isolate SIVsmE660, using a regimen intended to mimic typical HIV exposures resulting in infection. Viral loads in the vaccinees were significantly less at both the peak (1.9-log reduction; P < 0.03) and at the set point (2.6-log reduction; P < 0.006) than those in control naïve animals. Five of eight vaccinated macaques controlled acute peak viral replication to less than 80,000 viral RNA (vRNA) copy eq/ml and to less than 100 vRNA copy eq/ml in the chronic phase.
    
    Our results demonstrate that broad vaccine-induced cellular immune responses can effectively control replication of a pathogenic, heterologous AIDS virus, suggesting that T-cell-based vaccines may have greater potential than previously appreciated.
    
    jvi.asm.org/cgi/content/abstract/83/1...
    
19. flosz 23 juni 2009 14:28

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    Uit PER.C6 fact-sheet van mei, 2009.
    
    Currently fourteen PER.C6®-based products are in Phase I/II trials. This includes Merck’s candidate HIV vaccine produced on PER.C6® technology, which has been accepted by the FDA to be clinically tested on hundreds of healthy and immune-compromised volunteers.
    www.crucell.com/page/downloads/Factsh...
    
    www.youtube.com/watch?v=H6uPe7Euzd8
    
20. flosz 23 juni 2009 19:51

    auteur info

    • flosz

      Lid sinds: 13 feb 2008

      Laatste bezoek: 01 jul 2024

    • Aanbevelingen

      Ontvangen: 5298

      Gegeven: 2795

    •    Aantal posts: 7.005

    Piecing Together the
    HIV Prevention Puzzle
    AVAC Report 2009
    
    Ongoing Trials of Preventive HIV/AIDS Vaccines Worldwide (May 2009)
    Pag. 44
    
    A Trial by Any Other Name: HVTN 505 and the VRC candidate
    As AVAC Report went to press, the US Food and Drug Administration (FDA) had recently approved the
    protocol for HVTN 505, the test-of-concept study of the National Institutes of Health’s Vaccine Research
    Center’s (VRC) strategy that consists of three DNA “prime” immunizations and a single adenovirus
    5–vectored “boost.” (See timeline on page 37, and for more detailed information on the history of
    this candidate, please visit www.avac.org/vax_update.htm.)
    At roughly the same time, some members of the scientific community were discussing newer animal
    data that had some relevance to HVTN 505. Much of the talk centered on the results of a study by
    Harvard’s Dan Barouch and colleagues, in which animals received one of two variations on a DNA plus
    chimeric Ad (Ad5 plus an Ad48 hexon protein), or one of two variations on the chimeric Ad alone.5 In that
    experiment, presented at this year’s Keystone conference on HIV prevention, the animals that got the
    DNA plus chimeric Ad had survival rates and clinical outcomes comparable to the placebo group,
    while the chimeric Ad-alone animals had improved survival outcomes and, in an exploratory combined
    analysis, significantly lower viral loads. Barouch noted that his findings should be viewed as hypothesisgenerating
    rather than conclusive.
    Monkey studies are, by definition, small and inconclusive. Monkeys aren’t humans; the numbers are
    too small to draw firm conclusions; and in the absence of a correlate of protection, it’s difficult to know
    whether we’re measuring the right things. What’s more, the data concern a different vector; thus the
    strategy cannot be directly compared with the VRC strategy.
    So why were Barouch’s data of interest in the context of HVTN 505?
    Primarily because monkey data considered relevant to the VRC vaccine strategy to be tested in HVTN
    505 have been part of the scientific rationale for moving the trial forward.6,7,8 Monkey data were cited
    extensively at the December 2007 meeting of the AIDS Vaccine Research Subcommittee (AVRS) of the
    NIH and mentioned in the fact sheet that the HVTN produced on 505 one year later. Over the past year,
    AVAC has voiced concern about the lack of clear materials to help lay audiences understand HVTN 505.
    These include the lack of clarity in explanations of both the scientific rationale and the ways that the trial….meer pag.39
    www.avac.org/pdf/reports/2009_Report/...
    
    The HVTN 505 Study
    www.hvtn.org/media/pr/HVTN505studyfly...
    
    Presentatie Barouch uit nov. 2008:
    Novel Adenovirus Vector-Based Vaccines for HIV-1
    www.hvtn.org/meeting/ppt/nov08/thuam/...
    
21. Alpen 23 juni 2009 23:23

    auteur info

    • Alpen

      Lid sinds: 21 mei 2008

      Laatste bezoek: 10 dec 2024

    • Aanbevelingen

      Ontvangen: 815

      Gegeven: 100

    •    Aantal posts: 781

    "Merck's HIV vaccine candidate was in phase I and II studies when discontinuation of the trials was announced on 21 September 2007. The discontinuation of the studies was not related to the use of Crucell's technology."
    
    www.crucell.com/R_and_D-Clinical_Deve...
    
    Dus of bovenstaande pagina moet worden geupdate, of de PER.C6 fact-sheet van mei 2009 wacht al bijna twee jaar op een correctie. Hoop het eerste, vermoed het laatste.