Important note: Information in this article was accurate in December 2000. The state of the art may have changed since the publication date. IAVI Report - December 2000 / January 2001
Bonnie Levings
Nairobi — On 25 January 2001 the Kenyan Government endorsed plans for a Phase I trial of an HIV-DNA vaccine based on subtype A, the predominant strain in East Africa. Their action cleared the way for the trial to begin. Last month the study was approved by Kenya's National Council on Science and Technology and the Kenyatta National Hospital's Ethics and Research Committee.
The trial is the first one to test a vaccine made from an HIV strain common in Africa, and only the second HIV vaccine clinical study to take place on the African continent. The vaccine was developed through an IAVI-sponsored Vaccine Development Partnership (VDP) between Oxford University in the UK and the University of Nairobi in Kenya. The University of Nairobi's new HIV Vaccine Evaluation Unit, housed in the Department of Medical Microbiology, will carry out laboratory work for the trial, including T-cell measurements by ELISpot.
The vaccine has already entered Phase I testing in Oxford, UK. Since 31 August 2000, 17 of the 18 planned volunteers have been immunized, and so far no adverse effects observed.
The Oxford and Nairobi trials mark the first steps in testing a combination (prime-boost) vaccine with two components: the HIV-DNA and the same construct in a viral vector (the Modified Vaccinia Virus Ankara strain, or MVA). Full clinical testing will involve three separate studies — the HIV-DNA vaccine alone, HIV-MVA alone and then both, given to volunteers a few weeks apart. Each step will begin with a trial in the UK, followed by a Kenyan trial several months later. The lag makes it possible for preliminary safety data to inform the Kenyan approval process.
The second component of the combination vaccine, the HIV-MVA, received UK regulatory approval in September 2000. That Phase I trial is expected to begin in late February, once further data on volunteers given HIV-DNA are evaluated by the trial's Data Safety and Monitoring Board. Each of the components is designed to stimulate broad cytotoxic T cell (CTL) responses to multiple HIV epitopes. Both include most of the gag gene (from a clade A consensus sequence) fused to a string of 25 partially overlapping CTL epitopes from gag, pol, nef and env. The epitopes were identified in people infected with subtype A HIV strains circulating in Kenya, but many of them are relatively conserved among other HIV subtypes. (For a complete description of the vaccines, see Nature Med. 6: 952, 2000).
The scientific rationale for a CTL-based AIDS vaccine initially grew out of studies with sex workers in Nairobi and elsewhere in Africa. A small minority of these women remain seronegative despite continual exposure to HIV, and were found to have significant levels of HIV-specific T-cells in their bloodstream. The Nairobi study has been ongoing for over ten years and involves a collaboration among the groups of Andrew McMichael, Sarah Rowland-Jones and Rupert Kaul from Oxford and J.J. Bwayo, Omu Anzala and Frank Plummer in Nairobi (see IAVI Report, Jan-Mar 2000).
The trial preparations also involved negotiations over intellectual property (IP) issues, catalyzed by a series of articles in the Kenyan press starting in October 2000. The articles criticized a patent filed in December 1999 by the UK's Medical Research Council (MRC) covering the HIV sequences used in the vaccine. The patent lists Oxford researchers Andrew McMichael and Tomas Hanke, but no Kenyan investigators, as co-inventors. The articles expressed concern over the issue of ownership, which affects Kenyan rights to the vaccine, and over inventorship and credit for the work.
In response, the three partners in the project (the MRC, the University of Nairobi and IAVI) issued a joint statement reiterating their commitment to developing an AIDS vaccine together and stating that the original patent was "filed in good faith to protect the candidate DNA vaccine from unauthorized third-party exploitation." But they also acknowledged that the formal basis of the partnership — bilateral memoranda between MRC and Nairobi and between IAVI and MRC — was insufficient, since there were no written agreements among all three parties.
That acknowledgement led to the formation of an Intellectual Property Task Force, which met on 12-14 November 2000. The Task Force agreed that the partners should be equal owners of the vaccines and share any future revenues they generated. Under patent law, "ownership" is determined contractually and can be shared however the partners choose. In contrast, "inventorship" is strictly defined under patent law, and subsequent legal consultation led to the conclusion that the patent's inventors should not be changed. The Task Force is currently working on a "Memorandum of Understanding" which will encompass these agreements and provide a framework for IP decisions in the future.
Bonnie Levings is working for a Masters degree at Columbia University's School of Public Health and is a former member of IAVI's development staff. Before joining IAVI she was a volunteer with the US Peace Corps in West and Central Africa.
001210
IAVI2000-120103
©2000. The IAVI Report.
ĘGiS is made possible through unrestricted grants from Roxane Laboratories, Inc., iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2000. This material is designed to support, not replace, the relationship that exists between you and your doctor.
ĘGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.
Copyright ©1990, 2000. ĘGiS & the Sisters of Saint Elizabeth of Hungary. All materials appearing on ĘGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ĘGIS and the Sisters of Saint. Elizabeth of Hungary, or the party credited as the provider of the content.
