August, 2007 - ACRIA Update
from: AIDS Community Research of America - www.acria.org
Summer 2007 - Vol.16 No. 3

What Happened to the Vaccine?
by Richard Jefferys

When HIV was first discovered in the early 1980s, scientists were optimistic that a vaccine to prevent infection could be developed in a matter of years. Unfortunately, that optimism was misplaced, and HIV has turned out to be a tricky foe for vaccine researchers.

The Antibody Approach Hits a Snag
At the time of HIV’s discovery, it was thought that most vaccines worked by triggering a type of immune response called an antibody response (we now know that T cells and other parts of the immune system also play a role). Antibodies are tiny Y-shaped molecules made by a type of immune system cell called a B cell. The job of antibodies is to float around the bloodstream and glom onto pathogens, disabling them and marking them for destruction. Initial experiments in the laboratory showed that HIV grown in a lab dish could be effectively blocked by antibodies that would attach to HIV’s outer protein, called the envelope protein. Scientists designed vaccines based on a molecule on HIV’s envelope called gp120 in the hopes that these vaccines would trigger the development of similar antibodies in people, thereby protecting them if they were exposed to HIV.

But before these vaccines could be tested in clinical trials, researchers realized that HIV adapts itself to life in a lab dish in a way that makes it more vulnerable to antibodies than it is in the human body. HIV taken directly from people could not be blocked by the anti-gp120 antibodies that worked against HIV grown in the lab. One company, VaxGen, that was developing a gp120 vaccine decided to respond to this new information essentially by behaving like a child - covering its ears and singing “la, la, la” in the hopes of not hearing bad news.

VaxGen took its vaccine, named AIDSVAX, all the way to two huge clinical trials designed to test whether it worked. One trial was conducted mainly in North America and most of the participants were gay men. The second trial took place in Thailand among people at risk for HIV infection because of intravenous drug use.

When the results finally became available in 2003, it turned out that the laboratory studies had been right. There were no differences in the number of people that became HIV infected in the trials whether they received AIDSVAX or a placebo (dummy) vaccination. Shamefully, VaxGen attempted to sift through the results of the North American study and suggest that AIDSVAX had shown some protective effect in people of color; this turned out to be a false claim based on a very small number of nonwhite individuals that had enrolled in the trial.

T cell Responses Take a Turn
While this may sound disastrous, all was not lost because many other scientists continued to work on different vaccine approaches. Over the past decade or so, it has been found that there is another type of immune response against HIV that might be protective. These immune responses are called T cell responses.

T cells come in two main flavors: CD4 cells (which are monitored in people with HIV as a marker of disease progression) and CD8 cells. CD4 cells act like quarterbacks calling the plays for CD8 cells and B cells. CD8 cells have a vitally important function: They can recognize virus-infected cells in the body and zap them with destructive proteins in order to eliminate them. For this reason, they are also sometimes called cytotoxic T cells (cyto comes from the Greek word for cell) or cytotoxic T-lymphocytes (CTL).

Several lines of evidence suggest that CD4 and CD8 cells targeting HIV can play an important role. In monkeys infected with a close relative of HIV called SIV (simian immunodeficiency virus), viral load increases dramatically if researchers artificially deplete the animals of their CD8 cells. People with HIV who do not develop immune deficiency - long-term nonprogressors - have been shown to have highly functional CD4 and CD8 cells that target the virus, and their CD8 cells can rapidly kill HIV-infected cells in a lab dish. People with HIV that progresses in the usual way also have CD4 and CD8 cells targeting HIV - sometimes very large numbers of them - but when looked at to see how well they work, it turns out they do a poor job of killing infected cells.

Additionally, CD4 and CD8 cells targeting HIV have been found in individuals - such as sex workers and the uninfected partners of HIV-positive people - who have been repeatedly exposed to the virus, but remain uninfected (although it is not yet known if these T cell responses are protecting these individuals, or if they just indicate that exposure to HIV has occurred).

The ALVAC Vaccine
As a result of this evidence, and because of the difficulty of blocking HIV with antibodies, a major focus of vaccine researchers has been on designing vaccines that can induce production of CD4 and CD8 cells targeting HIV. While CD4 cell responses can be triggered quite easily, it turned out to be tough to trigger the development of CD8 cell responses.

For most of the 1990s, the best that researchers could do was induce CD8 cell responses targeting HIV in around 20% of HIV-negative people who received an experimental vaccine called ALVAC. ALVAC is a type of vaccine called a viral vector. It is a harmless version of a bird virus called canarypox that has been altered so that it makes several different HIV proteins when injected into people (the proteins cannot form infectious HIV).

Although most researchers think it’ll be necessary to trigger CD8 cell responses in more than 20% of recipients for a vaccine to have any chance of working, ALVAC is now being tested in a large trial in Thailand to see if it can offer any protection against HIV infection. Anyone in the trial who becomes infected will also be monitored to see if receiving the vaccine improves his or her chances of becoming a long-term nonprogressor.

Merck Makes a Breakthrough
The big breakthrough for vaccines aiming to trigger CD8 cell responses came just after the turn of the millennium. Merck & Co. developed a different kind of viral vector vaccine, based on a weakened form of a virus called adenovirus (which in its natural form causes bad colds). This vaccine has been shown to trigger CD4 and CD8 cell responses targeting HIV in the majority (50-70%) of people who receive it. The HIV proteins that the vaccine makes are called gag, pol, and nef. Merck’s vaccine is now being tested in a trial involving 3,000 HIV-negative people at risk for HIV infection. The trial got under way in January 2005, and results are expected by 2010 at the latest. As with the ALVAC trial, this study will also evaluate whether the vaccine can completely protect against infection or improve a person’s chances of becoming a long-term nonprogressor.

The VRC Weighs In
A very similar vaccine has been designed by government researchers at the Vaccine Research Center (VRC) in Bethesda, which is part of the National Institutes of Health. The VRC approach uses a two-pronged strategy called “prime-boost” vaccination. The first vaccine that is given consists of just of a piece of DNA that can make certain HIV proteins when injected into the muscle. This DNA vaccine can induce anti-HIV CD4 and CD8 cells, but only at very low levels. The VRC then uses an adenovirus-based vaccine like Merck’s to boost these CD4 and CD8 cells to much higher levels.

The VRC’s vaccine includes more HIV proteins: It has gag, pol, and nef, but also includes envelope proteins from three different HIV subtypes from different parts of the world: subtypes A, B, and C. A trial to test the effectiveness of this vaccine involving 8,500 people is just getting under way; preliminary results may be available by 2011.

Therapeutic Vaccines
All of the T cell-based vaccines mentioned in this article (and several others) are also being studied as potential therapies. The goal of therapeutic vaccination is to improve the effectiveness of anti-HIV immune responses in people that are already infected with the virus. Studies typically vaccinate people while they are receiving antiretroviral drugs, so that anti-HIV T cell responses can develop while viral load is suppressed. ART is then interrupted to figure out if these new immune responses can control HIV better than it was being controlled before.

To date, some studies using ALVAC have shown a limited impact of therapeutic vaccination, while others have shown no effect (or even a detrimental effect in one case). Results from studies using the Merck and VRC vaccines have not yet been presented.

Conclusion
Results from these ongoing trials of T cell-based HIV vaccines will be critical for the future of HIV vaccine research. If some significant evidence of protection - against either infection or disease progression - is seen, researchers will be able to try to improve on those results and, depending on the degree of success, submit the results to the FDA for approval of the vaccine.

A vaccine that reduced viral load levels could have a beneficial impact on the spread of HIV infection because people with lower viral loads are less likely to transmit the virus. It would be a challenge, however, to develop educational materials about such partially effective vaccines because recipients would need to be informed that they were not fully protected against HIV. If no hint of an effect emerges from the trials of T cell-based vaccines, vaccine researchers will have to ratchet up efforts to develop antibody-based vaccines or alternative approaches (if any can be discovered).

There is no way of knowing what the outcome of these trials may be; most optimistically, many researchers do feel - based on results in animal models - that the vaccines may improve the chance that a vaccine recipient who becomes infected with HIV will become a long-term nonprogressor. More pessimistically, few scientists think that these T cell-based vaccines will offer complete protection against HIV infection, since antibodies are thought to be necessary for this to occur.

If these scientists are correct - and current evidence strongly suggests they are - then it is extremely unlikely that a completely protective HIV vaccine will become available in our lifetime. We’ll only find out for sure in a few years time, when the results of these trials are in.

For more information, visit the AIDS Vaccine Advocacy Coalition at: avac.org. Their AIDS Vaccine Handbook: Global Perspectives (2nd edition) contains a wealth of detail on all aspects of the search for a vaccine, from the ethics of clinical trials to the need for community activism.

Richard Jefferys is Coordinator of the Michael Palm Basic Science, Vaccines & Prevention Project at the Treatment Action Group.

August 2, 2007 - On September 30th, the AIDSWalk 2007, sponsored by the Community AIDS Partnership of the Capital Region wil bring together over 2,000 Capital Region Residents to remind our community that the AIDS epidemic is far from over. Please join us in celebrating the lives of persons living with HIV/AIDS in our community and help raise funds for needed local HIV/AIDS services. Visit our website at http://aidscouncil.org/help/volunteer. Funds raised will support the efforts of Capital Region AIDS organizations that provide needed services for AIDS and prevention and care Prizes will be given to participatnts who raise the most money. Refreshments and entertainment will follow the walk.  Registration Form

August 2, 2007 - Special Thanks to those who supported the 17th Annual Benefit in Saratoga on July 29th. Nearly 200 guests, including Honorary Chairs, Sheryl & Barry K. Schwartz and very special guests, Marylou Whitney and John Hendrickson enjoyed the evening festivities among fabulous automobiles at the Saratoga Auto Museum. The event raised over $72,000 and will support the programs and services of the AIDS Council.

SARATOGA SPRINGS - July 27, 2007 - The AIDS Council of Northeastern New York’s Annual Benefit in Saratoga will take place on Sunday, July 29th at the Saratoga Automobile Museum, in Saratoga Springs, New York. We know that Saratoga in August can be a parade of the latest fashion trends, but those attending this event will show some real style as they support this important cause. This year’s event, “Diamonds InThe Rust” will feature gourmet cuisine by Classé Catering, cocktails and music by the Bennington Wind Trio, as well as the popular silent auction and other surprises. Sixteen years after the first Saratoga Benefit, the needs for those living with HIV/AIDS continue. Despite medical advances that prolong and improve the quality of life, there is still much progress to be made. The AIDS Council works tirelessly to increase the independence of those living with HIV/AIDS, reduce the stigma attached to the virus, and most of all, provide education to prevent further spread of this public health epidemic. Event Co-Chair and longtime supporter of the ADS Council, Sheryl Schwartz adds, “Barry and I value the work of the Council so highly that we have continued to support its stellar efforts for over 11 years. We are proud to invest in the work of the committed men and women of the AIDS Council.”

Presenting sponsor for the event is the MAC AIDS Fund. The event is also sponsored by Rueckert Advertising & Public Relations, LLC; Abacus Information Systems, Inc, Brigar X-Press Solutions, CDPHP, CapitalCare Medical Group, Capital Region Living, Casswood Insurance Agency, LTD, the Desmond Hotel & Conference Center, Jaeger & Flynn Associates, Inc., Queen of Tarts, The Sandy Hill Foundation, Stewart’s Shops and Trustco.

The theme of this year’s event comes from the exhibit at the Auto Museum, Barn Finds, inspired by Tom Cotter’s book, The Cobra In The Barn which includes stories of automobile archeology. The show features his father’s 1939 Ford Woodie that was recovered in Puerto Rico as well as many unique automobiles restored to their former glory. Executive Director of the AIDS Council, Michele McClave says “Many of our clients lives echo the stories of the cars in this exhibit because despite the rust of the disease within, they are people of value - someone’s mother, brother, or partner, and deserve every opportunity to shine.”

Tickets can be purchased online at www.aidscouncil.org, or by calling (518) 434-4686 x 2424. Tickets can also be purchased at the door.

ALBANY - June 21, 2007 - 25 staff and family members participated in marching with the AIDS Council’s Project HOPE staff during the Pride 2007 Parade and Festival. We distributed 3,500 condoms and 1,000 packages of lubes to festival attendees, and tested more people than in previous years. The theme “Love Out Loud” was expressed through noise makers and bright and colorful Project HOPE T-shirts worn by AIDS Council staff and volunteers.

ALBANY - June 21, 2007 - We always knew that board member Steve Ammerman was a star, but he proved it once again with his performance at Dancing with the Albany Stars on June 3rd. His first place win not only raised over $4,500 for the AIDS Council, but helped to raise $15,000 for the local non-profit, Dance Crazy, which brings ballroom dancing into schools to improve self-esteem, confidence and social skills. A great big thanks to Steve and his dance partner Paige Hammond. The competition, held at the Albany Mariott, was sponsored by the Arthur Murray Dance Studio in Latham.

HUDSON FALLS - June 21, 2007 - An Open House was held June 21st from 4pm to 6pm at our new office in Hudson Falls. Formerly in Glens Falls, the newly renovated office at 10 LaCrosse St offers a larger, brighter space for AIDS Council clientele. “Better accessibility and a private entrance are some of the features that will enable us to improve services for our clients,” said Michele McClave, Executive Director of the AIDS Council. All are welcome to stop in and learn about how the AIDS Council is changing lives for the better in our community.

ALBANY - May 31, 2007 - Steve Ammerman, WTEN anchor, and AIDS Council Board member will be dancing for the AIDS Council, June 3rd, at the Albany Marriott. Dancing with the Albany Stars is a fundraiser for the youth program Dance Crazy Inc., which teaches inner city 5th graders ballroom dancing and proper etiquette. The winner of the competition also gets to donate half of the money raised to his or her favorite charity, and Steve has chosen the AIDS Council. Come on out and cheer him on while he dances the Tango and Rhumba in this competition.

The competition is from 1pm to 3pm at the Mariott on Wolf Rd. in Colonie. Tickets are $10 at the door, and $5 a vote. The male and female winners from the afternoon competition have a dance off at a gala that night, also at the Marriott from 8:30 - 10pm. Included in the competition are: Nina Bouphasavanh, Jeff Stocker and Anya Tucker, also of WTEN; Kimberlee Brandt from It’s Just Lunch; Chrissy Cavotta and Jim Clark from FLY 92, and Paul Harding from Martin, Harding & Mazzotti, LLP. (If you wish to attend the gala and evening Dance-off, you must make reservations ahead of time as it includes a meal. For more information, log onto http://www.arthurmurraylatham.com.)

Good Luck Steve! We’re rooting for you!

ALBANY - May 31, 2007 - Executive Director Michele McClave and Director of Development and Marketing, Louise Bradford were featured on the Season Finale of Extreme Makeover Home Edition. The popular ABC show builds homes for families that are struggling, and featured the Oatman - Gaitan Family. With two of the boys HIV positive and a sinking foundation, this single mother was in great need. Their new home, built by thousands of volunteers from area businesses, will give them a fresh new start. The show also featured Camp Heartland, a camp in the Catskills for children and families that deal with HIV/AIDS. The show brought to light the many difficult issues of discrimination people with HIV/AIDS continue to face. The AIDS Council is grateful to the show for its efforts in this regard. A huge increase in hits on our website following the show tells us that the exposure was helpful indeed. Kudos to ABC and all Capital Region businesses and volunteers who made this all possible. We wish the Oatman - Gaitan family health and happiness in their new home.

ALBANY - May 16, 2007 - HIV/AIDS is not a subject most people like to talk about. Now that more people are living with AIDS rather than dying from it, many think it’s no longer a concern. So when Extreme Makeover Home Edition came to town to build a house for the Oatman – Gaitan family, who are dealing with HIV, the AIDS Council was more than happy for the opportunity to speak about these issues. Michele McClave, Executive Director of the AIDS Council of Northeastern New York, contacted the producer of EMHE to encourage her to use the episode to raise awareness, and offered to be a resource for accurate information about the disease. The welcome result was an interview with Eduardo Xol, one of the show’s designers, which is hoped to be included in the two hour season finale to be shown on WTEN (CBS) at 7pm on May 20th. In the interview McClave and Xol agreed that social consciousness regarding HIV/AIDS continues to lag far behind that which could eradicate this disease and spoke about the need that still exists. The producer also invited the AIDS Council to set up an information booth with literature about HIV/AIDS at the build site for the benefit of the huge crowd of spectators. A link from the show’s webpage “A Better Community” (www.abc.go.com/abettercommunity/outreach.html) will encourage people to visit the AIDS Council website, and contribute. “There is still a lot of stigma attached to this disease, but it needs to stay on the radar screen.” states Ms. McClave, Executive Director of the AIDS Council. “With 50% of all newly infected people being under 25 years of age, it’s imperative that we increase awareness. With community support, we can help those afflicted with this disease to lead independent, productive lives. Through education, we can look to a future where new cases decrease, and ultimately cease. We are very grateful to Extreme Makeover Home Edition for shining a heartfelt light on this important issue, and sharing it with the world. More understanding and compassion will encourage more funding, and through more funding, we can provide additional services.”

The AIDS Council puts a lot of effort into educating young people and those considered to be most at risk for spreading the disease. Youth programs include such things as developing an informative but fun interactive website to spread AIDS awareness, and a peer counseling program. They also have a program for transitional services in which they work with those preparing for release from prison to make safe, healthy decisions. For those who have already contracted the disease, they offer everything from case management, to emergency housing assistance and rides to the doctor, with the primary objective to provide them with the tools to be self sufficient. Arthur, a client of the AIDS Council expressed his gratitude to the AIDS Council recently, saying “The emotional, spiritual and life management help you give to me are the most important. Just to get me connected with the medical team after all of my disastrous experiences is the greatest of services. Your gentle support is a blessing.”