By Kristen Jill Kresge
IAVI Opens Southern Africa Regional Office
IAVI recently launched a new program in Johannesburg, South Africa, to support expanding AIDS vaccine research, development, and advocacy efforts for southern Africa. The global public-private partnership already operates several regional offices worldwide in Nairobi, Kenya; New Delhi, India; Amsterdam, the Netherlands; and New York City where the global headquarters is located. The Johannesburg offices will provide an opportunity for IAVI to work closely with existing partners and programs in southern Africa, including the South African AIDS Vaccine Initiative (SAAVI), the Medical Research Council (MRC), the Desmond Tutu HIV Foundation in Cape Town, the Medical University of South Africa, the Zambia-Emory HIV Research Project, the University of Limpopo, and the Perinatal HIV Research Unit at the University of Witwatersrand.
Seth Berkley, Chief Executive Officer of IAVI, said that the new regional office will serve as a focal point for expanding AIDS vaccine programs and activities in southern Africa and will lead the organization's efforts to build capacity to conduct clinical trials in the region to the highest scientific and ethical standards. In an editorial published in South Africa's Business Day, Berkley also said the southern Africa program will take advantage of the region's "growing biomedical capabilities, strong regulatory systems and manufacturing base." South Africa is collaborating with India and Brazil, two other countries severely-affected by HIV/AIDS, to harness the power of their growing biotechnology sectors for the discovery of new vaccines.
South Africa is already hosting several HIV prevention studies, including a large Phase III microbicide trial and multiple AIDS vaccine trials. IAVI initiated a Phase II AIDS vaccine trial last year in South Africa with several partner organizations to evaluate the safety and immunogenicity of an adeno-associated virus vaccine candidate known as tgAAC09 that encodes clade C HIV genes, which is the primary subtype of the virus circulating in the region (see the IAVI database of AIDS vaccines in human trials for more information). The Vaccine Research Center at the US National Institutes of Health, in collaboration with the HIV Vaccine Trials Network (HVTN), is also conducting a Phase II trial in South Africa with their DNA and adenovirus serotype-5 vaccine candidates. Merck and the HVTN will begin a Phase IIb AIDS vaccine trial there later this year with their lead adenovirus-based AIDS vaccine candidate.
Nasal Administration of AIDS Vaccine Candidate
A Phase I study of an HIV protein-based vaccine was initiated in the UK in September by researchers from St. George's Vaccine Institute at the University of London in collaboration with Novartis Vaccines, Richmond Pharmacology Ltd., and the Commission of the European Union. The vaccine candidate is comprised of HIV gp140 protein with the V2 loop deleted, and is being delivered nasally along with LTK63, a heat-labile enterotoxin from Escherichia coli that has been shown to enhance immune responses at mucosal surfaces.
The trial will enroll 30 volunteers who will be randomized to receive either 3 nasal immunizations of the vaccine candidate and adjuvant, followed by 2 additional immunizations with the same protein vaccine administered intramuscularly, or placebo. The booster immunizations will be administered along with a liquid adjuvant known as MF59.
All volunteers will be followed for 32 weeks during which time researchers will evaluate the safety of this dosing regimen and collect preliminary information on the immunogenicity of both the vaccine candidate and route of administration. Nasal administration generally induces stronger mucosal immune responses than intramuscular injection, which are widely considered to be a necessary response for a vaccine that could prevent sexual transmission of HIV. In the study investigators will be measuring the serum IgG neutralizing antibody responses to gp140 at several intervals as well as the IgA responses in both nasal and vaginal tissues to determine the frequency and type of immune responses induced at these surfaces.
Phase I AIDS Vaccine Trial in Infants Begins in Uganda
Researchers at Makerere University in Kampala, Uganda and Johns Hopkins University in the US recently initiated the first Phase I trial of an AIDS vaccine aimed at preventing the transmission of HIV from mother-to-child during breastfeeding. According to the World Health Organization, breastfeeding remains one of the major routes of HIV transmission to infants in developing countries; it is estimated that as many as a half of all HIV-infected infants acquire the virus not during delivery but through HIV-contaminated breast milk. Alternatives to breastfeeding, such as liquid formula or powdered milk, could easily prevent these infections, but in many settings these options are either prohibitively expensive or impractical because they require access to clean water. Also, HIV-infected women who do not breastfeed their babies are subjected to stigma in many cultures where it is common practice.
Another option for preventing HIV transmission from breastfeeding is administering antiretrovirals (ARVs) to the mother. Several studies have shown that treating HIV-infected women with ARVs throughout late pregnancy, labor, and during the period they are breastfeeding is a highly effective way to prevent HIV transmission to infants (see New strides in protecting infants from HIV, IAVI Report 9, 2, 2005). However, not all women have access to these drugs so a vaccine that could effectively protect babies during the period they are breast fed would be a major advance. To date only one vaccine trial has been conducted in infants.
This new randomized, placebo-controlled trial is being conducted through the HIV Prevention Trials Network (HPTN) and will enroll 50 infants born to HIV-infected mothers at Mulago Hospital in Kampala to evaluate the safety of a live-attenuated, recombinant canarypox virus vaccine candidate encoding HIV Env proteins from clades B and E. Forty of the infants will receive four doses of the vaccine candidate over three months and will be followed by researchers for two and a half years. The vaccine candidate, known as ALVAC-HIV vCP1521, was developed by Sanofi Pasteur and was previously evaluated in a safety trial in Uganda involving adult volunteers and in another study involving infants in the US. No serious safety issues were reported in either of these completed trials.
ALVAC vCP1521 is also now being tested in a Phase III efficacy trial in Thailand to see if it can protect adults against HIV infection. The Thai trial recently completed enrolling volunteers but final efficacy data will not be available for a few years. For more information on these and other ongoing AIDS vaccine trials, visit the IAVI Report vaccine trials database.
New Global Vaccine Conference to Accompany Annual Grand Challenges for Global Health Meeting
Grant recipients through the Grand Challenges in Global Health Initiative, a US$436.6 million program funded by the Bill & Melinda Gates Foundation to increase research on diseases that primarily affect developing countries, recently convened their annual meeting in Washington, DC to highlight progress on the 48 ongoing projects. Grantees include scientists from 33 countries who are working to tackle either scientific or technological challenges that could enhance global public health. Plans for this innovative funding mechanism were initially announced at the World Economic Forum in 2003 and the first round of grants were awarded last year in collaboration with the US National Institutes of Health (NIH).
The Gates Foundation also recently awarded the Keystone Symposia on Molecular and Cellular Biology, a US non-profit organization that hosts many high-profile scientific conferences, a three-year grant of $2.6 million to further expand their offerings of meetings that focus on global health. Keystone already sponsors several conferences concerning infectious diseases, including the annual symposia on HIV Pathogenesis and HIV Vaccines that are held in conjunction each spring. IAVI Report Travel Awards will be provided to scientists from developing countries to attend this meeting in 2007.
With the new funding from the Gates Foundation, Keystone will sponsor an additional meeting on vaccines, called "Challenges of Global Vaccine Development," which will be held either immediately before or after the next Grand Challenges in Global Health Meeting. The first annual conference will take place from October 8-13, 2007 in Cape Town, South Africa and will involve 300 scientists, many of whom are investigators on one of the Grand Challenges projects. The Keystone Symposia will also use part of this grant to provide scholarships and travel awards to researchers from developing countries, and specifically to graduate students and post-doctoral fellows who are completing their studies in Africa.