NIAID Launches First Phase II Trial Of A 'Global' HIV/AIDS Vaccine

The experimental vaccine was developed by scientists at NIAID's Daleand Betty Bumpers Vaccine Research Center (VRC) and is being studied inthe HIV Vaccine Trials Network (HVTN), a clinical researchcollaboration funded by NIAID's Division of AIDS (DAIDS).

"This trial marks an important step in the advancement towardan AIDS vaccine. The rapid development of this candidate vaccine--lessthan five years since the launch of the VRC--underscores our commitmentto hasten the day when we have an effective AIDS vaccine," says NIAIDDirector Anthony S. Fauci, M.D.

The unique vaccine combines synthetically modified elements of four HIVgenes found in subtypes A, B and C of the virus--the subtypes commonlyfound in Africa, the Americas, Europe and parts of Asia. These subtypesrepresent about 85 percent of HIV infections worldwide.

"This is the first Phase II study of a vaccine candidate that isbroadly relevant to the global AIDS pandemic because it combinescomponents of HIV strains found throughout the world," says VRCDirector Gary Nabel, M.D., Ph.D. "We look forward to working with ourpartners in the United States and abroad as we take this vaccine intothe next phase of clinical evaluation."

The trial, known as HVTN 204, is being coordinated with two otherplanned clinical studies, an unprecedented collaboration amongresearchers in three clinical trial networks and NIAID. TheInternational AIDS Vaccine Initiative plans to conduct a Phase I studyof the VRC vaccine at sites in Kenya and Rwanda, and the U.S. MilitaryHIV Research Program plans Phase I and II studies at sites in Uganda,Kenya and Tanzania; the studies are contingent on the appropriateregulatory and ethical approvals being granted in these countries.

About the Vaccine

The three harmonized trials will be testing a "prime-boost" strategycomposed of two vaccine components given at different times. Bothcontain synthetic versions of four HIV genes: gag, pol, nef and env.The gag, pol and nef genes come from HIV subtype B, the primary virusfound in Europe and North America. Env, the fourth gene, codes for anHIV coat protein that allows the virus to recognize and attach to humancells. The vaccine incorporates modified env genes from subtypes A andC, most common in Africa and parts of Asia, as well as subtype B.

The two vaccine components differ in how the genes are packaged. Onecontains only the naked gene fragments, which cannot reconstitute intoan infectious virus. The other uses a weakened type of respiratoryvirus known as adenovirus as a vector to shuttle the non-infectiousgene fragments into the body.

Adenoviruses cause upper respiratory tract illness, such as the commoncold. However, because the vaccine contains only HIV gene fragmentshoused in an adenovirus that cannot replicate, study participantscannot become infected with HIV or get a respiratory infection from thevaccine.

"The use of adenovirus vectors appears to be the most promising advancein recent years in the search for an HIV vaccine," says Peggy Johnston,Ph.D., director of the Vaccine and Prevention Research Program inDAIDS, NIAID. Lawrence Corey, M.D., principal investigator of the HVTN,adds, "We are excited to work with the VRC on this new vaccinecandidate. This prime-boost approach incorporating adenovirus vectorseems to generate the type and quantity of immune responses we feelwill be necessary to impact an infection like HIV. This study willdefine more completely the levels of immunity this novel approach willachieve in a broad range of people."

The DNA components of the vaccine were manufactured by the SanDiego-based Vical, Inc. The adenovirus vector was developed by VRC incollaboration with GenVec Inc., of Gaithersburg, Md., which alsomanufactured the adenovirus vector vaccine.

HVTN 204 Study Details

The HVTN 204 Phase II study will test the safety and ability of thevaccine to generate an immune response in 480 healthy, HIV-negativeadults ages 18 to 50. The researchers plan to recruit volunteers frompopulations particularly hard-hit by AIDS, including African Americansand other ethnic minorities.

The study is being led by Michael Keefer, M.D., of the University ofRochester, 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 isdesigned to include 13 HVTN sites, provided that regulatory and ethicalapproval 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 inthe Americas (Haiti, Jamaica, Brazil and the United States) and half insouthern Africa (Botswana and South Africa). The geographic diversityof participants allows the researchers to evaluate whether the immuneresponses generated to the vaccine vary according to the amount ofprior exposure to adenovirus, as measured by pre-existing levels ofadenovirus antibodies. Africans, for example, generally have hadgreater exposure to adenovirus than people living in North America.

The participants, divided into two groups, will receive fourinjections spread out over a period of six months. One group willreceive three injections of the naked DNA component followed by abooster injection of the adenoviral vector component. The second groupwill receive four injections of a placebo vaccine consisting of sterilesaltwater. Because the study is "double blind," neither theparticipants nor the researchers will know whether a volunteer isreceiving 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.

NIAIDis a component of the National Institutes of Health, an agency of theU.S. Department of Health and Human Services. NIAID supports basic andapplied research to prevent, diagnose and treat infectious diseasessuch as HIV/AIDS and other sexually transmitted infections, influenza,tuberculosis, malaria and illness from potential agents ofbioterrorism. NIAID also supports research on transplantation andimmune-related illnesses, including autoimmune disorders, asthma andallergies.

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.