University of Massachusetts Medical School begins clinical trial of multiclade AIDS vaccine
In April 2004, scientists at the University of Massachusetts Medical School (UMMS) began recruiting 36 healthy, HIV uninfected volunteers for a Phase I human trial of a new preventive AIDS vaccine formulation.
The vaccine strategy was developed by Shan Lu, PhD, associate professor of medicine and the head of the HIV vaccine effort at UMMS, in collaboration with Advanced BioScience Laboratories (ABL). The ABL-UMMS team was funded by a HIV Vaccine Design and Development Team (HVDDT) contract from the National Institute of Allergy and Infectious Diseases. This vaccine formulation was recently approved as an investigational new drug (IND) by the US Food and Drug Administration. The strategy uses a polyvalent DNA prime followed by a protein boost; both candidates are based on five different strains of HIV originally isolated from infected patients in five locations around the world. The researchers hope that the polyvalent prime-boost combination will induce both neutralizing antibody and cellular responses against HIV. It is not yet known whether the global diversity of HIV clades will require AIDS vaccines to be matched to locally circulating strains, or whether it will be possible to develop a single, universal vaccine against all HIV subtypes. Lu and his collaborators hope that future trials of their multiclade vaccine will help address this question. The DNA component of the vaccine contains one HIV gag gene (clade C) plus 5 HIV env genes (one clade A, two clade B, one clade C, and one clade E). The DNA inoculations are boosted with 5 different recombinant gp120 proteins (same isolates as the DNA component). The protein boost is administered in combination with QS21 adjuvant. —Roberto Fernandez-Larsson*
Major industry enters into partnership with the microbicides field
On 29 March 2004, the International Partnership for Microbicides (IPM) and Tibotec Pharmaceuticals, a subsidiary of Johnson & Johnson, announced a collaborative agreement to advance TMC120, a Tibotec product, into trials as an experimental microbicide. This is the first time that a major company has partnered with the microbicides field, which is largely made up of small biotech firms, non-profit groups and academic researchers. Under the agreement, Tibotec has granted the IPM a royalty-free license to develop TMC120 as a microbicide in resource-poor settings.
TMC 120 is an experimental antiretroviral drug in the non-nucleoside reverse transcriptase inhibitor (NNRTI) class. Several other NNRTIs are also being developed as potential microbicides. Many developers in the field believe that the most effective microbicides will combine several compounds with different targets and modes of action. It is hoped that topical formulations of NNRTIs will protect against HIV infection by inactivating virus in semen.
Phase I trials of TMC 120 are currently in progress; should the experimental candidate prove safe, it will move into expanded trials. Under the agreement, Tibotec will bear the costs of current trials and the cost of the compound through Phase II trials; IPM will assume all other development costs. IPM will retain the rights to manufacture and distribute the product in the developing world should it prove effective, a provision designed to ensure that the product will be affordable and readily available to women in the developing world. Tibotec will have the option of marketing the product in developed countries; if exercised, IPM will recover some of the development costs and receive a royalty which can be used to further IPM's mission.
The IPM is a public-private partnership that was founded in 2002 to accelerate microbicide product development. Other activities include support of a center for in vitro drug screening and collaborations with pharmaceutical companies and other organizations. —Emily Bass*
New staff at the South African AIDS Vaccine Initiative
In March the South African AIDS Vaccine Initiative (SAAVI) announced the appointments of two new team members: Gatsha Matzithulela, PhD as Deputy Director and Elize Levendal as the new Head of SAAVI Community Preparedness Program, replacing Ashraf Grimwood. Ms Levendal is a nurse and former Executive Director of the Western Cape branch of South Africa’s National Progressive Primary Health Care Network; she has also served as the womens' sector representative at the South African National AIDS Council. A molecular biologist, Dr Matzithulela also holds an MBA; he has a background in intellectual property and marketing issues in the field of biotechnology. At SAAVI, Dr Matzithulela will have a particular focus on vaccine development. —Emily Bass*
New executive director for the AIDS Vaccine Advocacy Coalition
Mitchell Warren is the new Executive Director of the AIDS Vaccine Advocacy Coalition, a US-based international non-profit organization that mobilizes support for and awareness of AIDS vaccine research in the US and internationally. Warren was previously the Senior Director for Vaccine Preparedness at IAVI, where he helped direct efforts to increase community and national involvement in AIDS vaccine clinical trials in Africa, Asia and Latin America. Prior to joining IAVI, Warren was the Vice President for International Affairs at the Female Health Company where he worked with governments, donor agencies and non-governmental organizations to expand women’s HIV prevention options and to design and implement delivery programs for the female condom. In his new role, Warren will continue to focus on global advocacy and says that AVAC will “find increasing ways to have communities around the world be meaningfully engaged in the vaccine development process.” —Emily Bass*
*Emily Bass is senior writer of the IAVI Report.
Roberto Fernandez-Larsson, Ph.D., is the IAVI Report Web editor