VAX is a monthly bulletin published by the International AIDS Vaccine Initiative (IAVI) featuring shorter, nontechnical versions of articles from the IAVI Report. VAX is currently available in English, French, German, Portuguese, and Spanish as a pdf or an e-mail bulletin. If you would like to receive VAX by e-mail, please send a request including language preference to: iavireport@iavi.org.
The Vax bulletin is available in English (HTML and PDF), Deutsch (PDF), Français (PDF), Español (PDF), and Português (PDF).
Over the past several years the number of people in developing countries receiving antiretroviral (ARV) therapy has steadily increased due to efforts mounted by the Global Fund to Fight AIDS, Tuberculosis, and Malaria and other international programs, including the US President's Emergency Plan for AIDS Relief (PEPFAR). But the number of new HIV infections continues to be high—four million individuals were newly infected last year—and this has shifted attention back to halting transmission of the virus.
The first AIDS vaccine candidate developed by Russian scientists, known as Vichrepol, is now in Phase I clinical trials. Descriptions of this candidate and the ongoing study were presented in posters at both the International AIDS Conference in Toronto (see Spotlight article) and the AIDS Vaccine 06 conference held from August 29 to September 1 in Amsterdam. Vichrepol is a recombinant protein vaccine comprised of fragments of HIV proteins administered with an adjuvant known as polyoxidonium, which is already used with a licensed influenza vaccine.
Industry's involvement in the development of an AIDS vaccine is seen by many in the field as imperative since much of the expertise in testing and manufacturing licensed vaccines is found within large pharmaceutical companies. Although several companies are actively engaged in AIDS vaccine research and development, the Blueprint calls for an increased level of commitment.
As HIV continues to infect millions of people throughout the world, more and more of the newly infected are between the ages of 15 and 24. Young people in this age group now account for almost half of all new HIV infections, with nearly three million becoming HIV infected each year. Despite these startling statistics, AIDS vaccines have so far not been tested in adolescent volunteers.
This special issue provides a guide to the AIDS vaccine-related sessions at the XVI International AIDS Conference in Toronto. Readers not attending the conference can go to www.aids2006.org and search by abstract number, author, or keyword for further information on these sessions. The September issue of VAX will feature coverage of the key findings from the meeting related to AIDS vaccine research and other HIV prevention technologies.
Almost all infants, everywhere in the world, have been infected with rotavirus by age five. This common pathogen can cause a range of symptoms, from mild gastrointestinal discomfort to the diarrheal disease known as acute gastroenteritis that can lead to serious dehydration. And although even the most severe cases of the disease can usually be treated easily with replenishment of fluids or electrolytes, rotavirus kills 600,000 children each year, the vast majority in developing countries where access to healthcare services is limited. This single virus accounts for about 5% of all childhood deaths worldwide.
In a final report, leaders of the G8 nations who gathered in St. Petersburg, Russia from July 15-17 pledged continued support for HIV prevention, treatment, and care, highlighting in particular the development of AIDS vaccines and microbicides as priorities in the fight against the pandemic. The need for vaccines to prevent other diseases that increase an individual's risk of HIV infection was also emphasized.
Malawi recently launched a nation-wide campaign to encourage the country's citizens to undergo voluntary counseling and testing (VCT) for HIV infection (see November 2005 Primer on Understanding HIV Testing). The aim of this week-long testing drive, announced by the Health Minister, is to increase access to the available HIV prevention, treatment, and care services, and was initiated after surveys found that only 15% of the 12 million people in the country have already received VCT.
The Bill & Melinda Gates Foundation awarded US$287 million in grants over the next five years to 16 different research teams, encompassing 165 investigators from 19 countries, to support innovative approaches to overcoming the scientific obstacles in AIDS vaccine research and to accelerate the development of new candidates. These grants are the Foundation's largest contribution to date for HIV/AIDS research and bring together many of the leading teams that are currently working to develop an effective vaccine.
There is a tremendous need for vaccines that can effectively prevent diseases throughout the world. But for a variety of reasons, including inadequate healthcare systems, national immunization policies, or the inability to pay for the new vaccines, some governments may not readily adopt them for use in their countries. "We recognize that developing countries have to make hard choices," says John Wecker of the US-based non-profit organization Program for Appropriate Technology in Health (PATH), who is currently working with several countries to plan for introduction of rotavirus vaccines.
Just days before researchers and activists around the world marked the 25th year of battling the HIV epidemic, the United Nations General Assembly Special Session (UNGASS) on HIV/AIDS convened in New York City to revise the "declaration of commitment" on AIDS, which was created at the first meeting of this kind held five years ago. This high-level event, which took place from May 31 to June 2, was attended by more than 10 heads of state and leaders from more than 140 UN member states, as well as over 1000 representatives from activist groups and other civil society organizations.
The first vaccine capable of preventing cervical cancer recently received approval and licensure by the US Food and Drug Administration (FDA) for use in females ages 9-26. Gardasil, the quadrivalent vaccine manufactured by Merck, also prevents the development of precancerous genital lesions and genital warts caused by four types of the human papillomavirus (HPV), which is one of the most common sexually-transmitted infections in the world (see February 2006
When AIDS was first described in the medical literature 25 years ago, there was not a single medicine to treat people infected with this new human virus. Since then more than 20 antiretrovirals (ARVs) have been licensed by the US Food and Drug Administration for the treatment of HIV/AIDS. These drugs have dramatically improved the health of millions of HIV-infected people around the globe and are now becoming increasingly available in developing countries where the need is still the greatest.
GeoVax, a US-based biotechnology company, recently began enrolling volunteers for a Phase I trial to evaluate the safety and immunogenicity of the company's AIDS vaccine candidates at four sites in the US.
On May 18th communities around the world are planning events to commemorate an annual day dedicated to the development of a safe and effective AIDS vaccine. IAVI-sponsored events are planned in India and Kenya, including the screening of the documentary Ending AIDS: The Search for a Vaccine to raise awareness and highlight advances in the field. The US National Institutes of Health is also sponsoring several community events throughout the US.
The Keystone symposium on HIV Vaccines is a major meeting on the calendar of HIV researchers from various scientific disciplines. For one week each year it offers them a chance to share ideas, discuss, and often debate, their work. A practical and crucial part of this work is the progress made in conducting clinical trials with AIDS vaccine candidates to test their safety, immunogenicity, and possible efficacy. This year's Keystone meeting provided a comprehensive roundup of ongoing AIDS vaccine trials and related activities and showcased the work of several collaborating organizations that are expanding existing trials or unveiling plans for new ones.
The projected number of individuals participating in a Phase I AIDS vaccine trial in Kenya and Rwanda, conducted by IAVI in partnership with the VRC, will be increased after approval was granted recently from the local institutional review boards in the countries. Project San Francisco began enrolling volunteers at the site in Kigali, Rwanda late last year—marking the start of the first AIDS vaccine trial in the country—and the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi began recruitment in January. Total enrollment for both sites was initially set at 64 volunteers but will now be increased to 104.
The African Union in partnership with the Joint United Nations Programme on HIV/AIDS (UNAIDS) initiated a unified call from leaders of many African nations to increase and improve HIV prevention services on the continent. On April 11 government leaders from several countries kicked off this initiative. Among these was Meles Zenawi, the Primer Minister of Ethiopia, who emphasized how the scale up of prevention services can have profound effects in dealing with the epidemic.
Active recruitment and enrollment of volunteers has now started at research sites in Lusaka, Zambia; Masaka, Uganda; Kigali, Rwanda; and Kangemi, Kenya for a multi-centre, epidemiological study of newly HIV-infected individuals being conducted by IAVI. Volunteers who were recently infected with HIV through incidental exposure were identified through participation in incidence studies where they were counseled on risk-reduction practices and tested for HIV at least four times a year.
Like any great scientific challenge, the search for an AIDS vaccine requires money, minds, and collaboration. These first two requirements are closely related, and as new streams of funding flow into the field more interest is being focused on this pursuit.
The World Health Organization (WHO) and the United Nations Joint Programme on HIV/AIDS (UNAIDS) recently sponsored a technical consultation with experts in the AIDS vaccine field to discuss the design and use of Phase IIb "test of concept" trials in evaluating AIDS vaccine candidates and their implications for approval and licensure.
Almost a dozen clinical trials are now ongoing to see if drugs to suppress herpes simplex virus-2 (HSV-2) can reduce the risk of HIV transmission and infection (see VAX November 2005 Spotlight article, HIV prevention in a pill?). These studies were initiated because of mounting evidence that there is an association between HSV-2 and HIV infection.
Almost a dozen clinical trials are now ongoing to see if drugs to suppress herpes simplex virus-2 (HSV-2) can reduce the risk of HIV transmission and infection (see VAX November 2005 Spotlight article, HIV prevention in a pill?). These studies were initiated because of mounting evidence that there is an association between HSV-2 and HIV infection.
Two vaccine candidates designed to protect against a common pathogen known as human papillomavirus (HPV) have proven highly effective in large clinical trials and should be approved and licensed in the US and Europe later this year. This is considered a major medical advancement since HPV is a sexually-transmitted infection that is now widely accepted among scientists as a necessary, but not itself sufficient, step in the development of cervical cancer. This is the leading cause of cancer-related mortality among women in developing countries and accounts for more than 290,000 deaths worldwide each year.
Pharmexa-Epimmune, a US subsidiary of a Danish vaccine and immunotherapy company, recently initiated a Phase I AIDS vaccine trial to evaluate the safety and immunogenicity of two candidate vaccines that will be tested either alone or in combination. This trial will enroll 124 volunteers at 3 sites in the US and in Lima and Iquitos, Peru, in partnership with the HIV Vaccine Trials Network (HVTN).
The vaccine candidate, TBC-M4, uses a weakened and non-infectious MVA virus as a vector to deliver HIV fragments to the immune system, but importantly the candidate can not cause HIV infection because only part of the virus is used. The fragments included in the candidate are from clade C HIV, which is the predominant virus circulating in India and China, as well as parts of Africa. Researchers and an independent advisory board will evaluate the safety of the candidate at the low dose before administering a higher dose to volunteers in this trial.
In 2005, 13 new trials of preventive AIDS vaccine candidates began in 9 countries around the world. Two of these involved vaccine candidates that entered Phase II trials, an intermediate stage of clinical evaluation. India, China, and Rwanda started their first AIDS vaccine trials last year and South Africa began that country's first Phase II AIDS vaccine trial. Several of these newly initiated trials involved novel vaccination strategies, including prime-boost regimens where two candidates are administered separately to try to improve the immune responses induced.
When HIV began spreading rapidly mostly among gay men in the US there were no therapies available. As scores of people started dying from AIDS, members of these affected communities staged protests and organized die-ins, demanding that the government and the nation's massive pharmaceutical industry put its weighty scientific resources into developing treatments for this lethal virus and that community members have a say in the process.
All organisms, ranging from the simplest unicellular ones to humans, are subject to relentless attack by pathogens(1) and so have consequently evolved the means to defend themselves by dedicating a large number of genes to ensuring their survival(1,2). In higher animals, starting with the jawed fish, these defense mechanisms have resulted in the development of two elaborate but critical arms of the immune system, innate and adaptive immunity.
Tony Fauci, MD, has been at the forefront of the global response to HIV/AIDS ever since the first cases were described 25 years ago. Among many achievements related to the pandemic, he was responsible for the early expansion of the US National Institutes of Health's (NIH) HIV research capacity and won plaudits from many for engaging with HIV treatment activists and fostering dialog with them in the mid 1980s.
Preventive vaccines can alleviate needless suffering and deaths and save millions of dollars in health expenditures. For a variety of reasons, however, countries do not always rapidly adopt them. The reasons include inadequate health care infrastructure, country-level immunization policies, inability to pay, and individual and community attitudes towards the acceptance of the product.
GeoVax, a US-based biotechnology company, recently began enrolling volunteers for a Phase I trial to evaluate the safety and immunogenicity of the company's AIDS vaccine candidates at four US sites in conjunction with the HIV Vaccine Trials Network (HVTN).
An untreated HIV infection is often pictured as a long, bloody battle. The virus infects a new host, the immune system strikes back and the fight enters into a prolonged struggle. Then, after many years, the immune system finally collapses and the virus is declared the winner.
This is a milestone year in HIV/AIDS. Although HIV has been within the human population since the 1930s, 2006 marks the 25th year since AIDS was first medically recognized. Tristram Parslow of Emory University, one of the co-organizers of the Keystone Joint Symposia on HIV Pathogenesis and HIV Vaccines, opened the symposia by referring to the signature year, saying that it was 25 years since HIV "emerged" and ushered in the "dawn of the HIV epidemic," and reminding the audience that 40 million people are now infected worldwide and that 35 million of those don't know it.
Researchers at Keystone provided a comprehensive roundup of ongoing AIDS vaccine trials and related activities. Barney Graham of the Vaccine Research Center (VRC) at the US National Institutes of Health (NIH) kicked off this series of updates with a look at the many ongoing trials with the VRC's lead vaccine candidate—a DNA plasmid vaccine containing clade B gag, pol, and nef and env genes from clades A, B, and C, followed by an adenovirus serotype 5 (Ad5) vector vaccine boost carrying the same genes excluding nef.
Recently, an 18 month old girl, one of the few children paralyzed by poliomyelitis last year in India, was filmed by an international camera crew documenting the final human-to-human chains of polio transmission. She had been hidden by her parents from the polio vaccination team each time it passed because of a misunderstanding about the safety of the vaccine, and her left leg had been paralyzed two months earlier by polio. Already by the time of filming, in the arms of her mother, she had learned to move her paralyzed leg by slipping her non-affected leg behind and lifting upward.
CD8+ T cells are often thought of as the frontline weaponry in the battle to fend off pathogens and malignant cells, but crucially they require helper activity from CD4+ T cells. This help is especially important in assisting the development of long-term CD8+ T-cell memory. The antigenic ligands for the CD8+ and CD4+ T cells involved in help-dependent responses must be co-presented by the same antigen-presenting dendritic cell (DC). Precisely how this is accomplished has not been fully understood.
Active recruitment and enrollment of volunteers has now started at research sites in Lusaka, Zambia; Masaka, Uganda; Kigali, Rwanda; and Kangemi, Kenya for a multi-centre, epidemiological study of newly HIV-infected individuals being conducted by IAVI. Recently infected individuals for this research study are identified through participation in incidence studies where they are counseled on risk-reduction practices and tested for HIV at least four times a year.
In the hunt for better vaccines, researchers are engineering viruses and bacteria into harmless vectors, delivery vehicles for genes from pathogens, to safely stimulate protective immunity. But as researchers attempt to domesticate these microbes to deliver genes for vaccines, possible immune reactions against those vectors become important obstacles to overcome.
When President John F. Kennedy vowed to put a man on the moon by the end of the 1960s, he mobilized the nation's top scientists and engineers to the task. The Manhattan Project in the 1940s and the Human Genome Project in the 1990s—each of these projects succeeded on the back of huge sums of money, the best scientific expertise, and an unprecedented level of collaboration among scientists.
The 13th Conference on Retroviruses and Opportunistic Infections (CROI), which took place from 5-8 February, often struck a historic chord as many plenary and keynote speakers acknowledged the passage of important landmarks in the battle against the AIDS pandemic.
José Esparza MD, PhD has been a leader in the international HIV arena for almost two decades and for much of that time has been a consistent champion for AIDS vaccines, particularly for developing countries. He currently wears two hats, one as Senior Advisor on HIV Vaccines at the Bill & Melinda Gates Foundation, as well as head of the interim secretariat for the Global HIV Vaccine Enterprise.
About 3% of people are chronically infected with hepatitis C virus (HCV), putting them at elevated risk of liver disease and cancer. There is currently no vaccine to protect against HCV infection and developing one has been challenging, partly because antibodies that neutralize one HCV strain don't work on the highly diverse range of viruses found in infected individuals.
The first candidate, known as EP HIV-1090, is a DNA plasmid vaccine comprised of antigens from Gag, Pol, Nef, and Vpr that code for proteins conserved among several HIV clades (A, B, C, D, F, and G). This candidate was tested in a previous Phase I trial with the HVTN in 42 volunteers. The second vaccine candidate, EP-1043, is a recombinant protein vaccine comprised of T helper cell epitopes from HIV clade B Env, Gag, Pol, and Vpu administered with an Alum adjuvant. This vaccine candidate is intended to interact with CD4+ T cells and cause their proliferation.
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Vol. 4(12), Dec 2006 
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