U.S. Department of Health and Human Services NATIONAL INSTITUTES OF HEALTH NIH News National Institute of Allergy and Infectious Diseases (NIAID) http://www3.niaid.nih.gov/ FOR IMMEDIATE RELEASE: Tuesday, October 11, 2005 CONTACT: NIAID News Office, 301-402-1663, niaidnews@xxxxxxxxxxxxx NIAID LAUNCHES FIRST PHASE II TRIAL OF A "GLOBAL" HIV/AIDS VACCINE A novel vaccine targeted to multiple HIV subtypes found worldwide has moved into the second phase of clinical testing, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), announced today. The study investigators plan to enroll a total of 480 participants at sites in Africa, North America, South America, and the Caribbean to test the safety and immune response to the vaccine. The experimental vaccine was developed by scientists at NIAID's Dale and Betty Bumpers Vaccine Research Center (VRC) and is being studied in the HIV Vaccine Trials Network (HVTN), a clinical research collaboration funded by NIAID's Division of AIDS (DAIDS). "This trial marks an important step in the advancement toward an AIDS vaccine. The rapid development of this candidate vaccine -- less than five years since the launch of the VRC -- underscores our commitment to hasten the day when we have an effective AIDS vaccine," says NIAID Director Anthony S. Fauci, M.D. The unique vaccine combines synthetically modified elements of four HIV genes found in subtypes A, B and C of the virus -- the subtypes commonly found in Africa, the Americas, Europe and parts of Asia. These subtypes represent about 85 percent of the HIV infections worldwide. "This is the first Phase II study of a vaccine candidate that is broadly relevant to the global AIDS pandemic because it combines components of HIV strains found throughout the world," says VRC Director Gary Nabel, M.D., Ph.D. "We look forward to working with our partners in the United States and abroad as we take this vaccine into the next phase of clinical evaluation." The trial, known as HVTN 204, is being coordinated with two other planned clinical studies, an unprecedented collaboration among researchers in three clinical trial networks and NIAID. The International AIDS Vaccine Initiative plans to conduct a Phase I study of the VRC vaccine at sites in Kenya and Rwanda, and the U.S. Military HIV Research Program plans Phase I and II studies at sites in Uganda, Kenya and Tanzania; the studies are contingent on the appropriate regulatory and ethical approvals being granted in these countries. ABOUT THE VACCINE The three harmonized trials will be testing a "prime-boost" strategy composed of two vaccine components given at different times. Both contain synthetic versions of four HIV genes: "gag, pol, nef" and "env". The "gag, pol" and "nef" genes come from HIV subtype B, the primary virus found in Europe and North America. "Env", the fourth gene, codes for an HIV coat protein that allows the virus to recognize and attach to human cells. The vaccine incorporates modified "env" genes from subtypes A and C, most common in Africa and parts of Asia, as well as subtype B. The two vaccine components differ in how the genes are packaged. One contains only the naked gene fragments, which cannot reconstitute into an infectious virus. The other uses a weakened type of respiratory virus known as adenovirus as a vector to shuttle the non-infectious gene fragments into the body. Adenoviruses cause upper respiratory tract illness, such as the common cold. However, because the vaccine contains only HIV gene fragments housed in an adenovirus that cannot replicate, study participants cannot become infected with HIV or get a respiratory infection from the vaccine. "The use of adenovirus vectors appears to be the most promising advance in recent years in the search for an HIV vaccine," says Peggy Johnston, Ph.D., director of the Vaccine and Prevention Research Program in DAIDS, NIAID. Lawrence Corey, M.D., principal investigator of the HVTN, adds, "We are excited to work with the VRC on this new vaccine candidate. This prime-boost approach incorporating adenovirus vector seems to generate the type and quantity of immune responses we feel will be necessary to impact an infection like HIV. This study will define more completely the levels of immunity this novel approach will achieve in a broad range of people." The DNA components of the vaccine were manufactured by the San Diego-based Vical, Inc. The adenovirus vector was developed by VRC in collaboration with GenVec Inc., of Gaithersburg, Md., which also manufactured the adenovirus vector vaccine. HVTN 204 STUDY DETAILS The HVTN 204 Phase II study will test the safety and ability of the vaccine to generate an immune response in 480 healthy, HIV-negative adults ages 18 to 50. The researchers plan to recruit volunteers from populations particularly hard-hit by AIDS, including African Americans and other ethnic minorities. The study is being led by Michael Keefer, M.D., of the University of Rochester, NY, and Gavin Churchyard, M.B.B.Ch., F.C.P., M.Med., Ph.D., of Aurum Health Research Ltd. in South Africa. The trial opened at the University of Alabama at Birmingham and is designed to include 13 HVTN sites, provided that regulatory and ethical approval is granted at each site: -- North America: Baltimore, MD; Boston, MA; Providence, RI; Birmingham, AL; Nashville, TN; and Rochester, NY -- South America: Rio de Janeiro and São Paulo, Brazil -- Caribbean: Port-au-Prince, Haiti; Kingston, Jamaica -- Africa: Gaborone, Botswana; and Cape Town, Soweto, and KOSH (Klerksdorp, Orkney, Stilfontein, and Hartbeesfontein), South Africa Half of the 480 trial participants will be enrolled in the Americas (Haiti, Jamaica, Brazil and the United States) and half in southern Africa (Botswana and South Africa). The geographic diversity of participants allows the researchers to evaluate whether the immune responses generated to the vaccine vary according to the amount of prior exposure to adenovirus, as measured by pre-existing levels of adenovirus antibodies. Africans, for example, generally have had greater exposure to adenovirus than people living in North America. The participants, divided into two groups, will receive four injections spread out over a period of six months. One group will receive three injections of the naked DNA component followed by a booster injection of the adenoviral vector component. The second group will receive four injections of a placebo vaccine consisting of sterile saltwater. Because the study is "double blind," neither the participants nor the researchers will know whether a volunteer is receiving the study vaccine or the placebo until the end of the trial. Information about enrolling in HVTN 204 can be found at HVTN's Web site, www.hvtn.org. For more information about the VRC and its candidate vaccine, visit www.vrc.nih.gov. News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov. NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies. The National Institutes of Health (NIH) -- "The Nation's Medical Research Agency" -- includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. 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