SciDev.Net

Vaccination for infectious diseases is a vital method of prophylaxis, and has transformed modern medicine. By contrast, research into vaccines against chronic diseases has been less successful, in part because of the increased complexity involved.

In this opinion piece, the authors outline the prospects for the development of chronic disease vaccines. These might not need to rely on the traditional method of inducing the body to produce antibodies, but rather on introducing monoclonal antibodies against specific proteins — this has so far worked well against Crohn's disease and rheumatoid arthritis.

The authors outline key hurdles in developing a successful therapeutic vaccine. Safety and efficacy are two obvious ones, but there is a third that is unique to vaccines for chronic diseases. Because these vaccines would block bodily chemicals — such as cytokines or hormones — it would not be acceptable for a vaccine to induce a life-long block (unlike a malaria vaccine, for example, where a lifelong block would be ideal).

These might be particularly useful in developing countries, say the authors. Because prophylaxis with vaccines is already a familiar concept, there should be no problem with patients' compliance, and judicious partnerships between public and private organisations could mean the vaccines are produced cheaply.

Launched to coincide with the 2004 International AIDS Conference in Bangkok, in this strategy document, the IAVI outlines plans to strengthen and expand the research and development pipeline of candidate HIV vaccines, and engage as partners those countries most affected by HIV/AIDS. Future scientific strategy includes focusing on vaccines that trigger neutralising antibodies, and understanding how live weakened vaccines work in animal models for clues to what is needed in a vaccine for protecting people.

In response to controversy over a trial in Cambodia that was halted earlier this year, this document, written for a broad audience, addresses a range of issues regarding tests of the antiretroviral drug tenofovir in healthy uninfected individuals. The clinical trials, taking place in Africa, Asia and the Americas, aim to see whether Tenofovir can protect against HIV infection in those who are at high risk of exposure to the virus — so-called Pre-Exposure Prophylaxis, or PREP. But its use raises a whole set of concerns regarding its potential impact on trial volunteers and their communities, including the prospects for encouraging drug-resistant strains of HIV to emerge and higher risk sexual behaviour.

This collection of 43 essays is by people involved in HIV/AIDS research, community education, clinical trials and advocacy, and aims to both inform and encourage global action. Written in an easy-to-read style, it introduces many of the major scientific, policy, social, ethical and economic challenges of developing an AIDS vaccine, with chapters covering issues such as HIV vaccine science, vaccine safety, ethics of clinical trials, informed consent, community action to encourage HIV vaccine development, and sources of information and help. Notable contributions from developing country authors include the personal experiences of a vaccine scientist involved in establishing the first HIV vaccine trials in Uganda, the vulnerability of women to HIV/AIDS in India , and the challenges of recruiting women to participate in clinical trials in Kenya. Illustrations include photographic accounts of the HIV virus and its life cycle, and clinical and laboratory tests on clinical trial volunteers.

This news feature aimed at a broad scientific audience likens the perplexing task of trying to develop an HIV vaccine to “flying without a compass”. HIV poses unique challenges, including its infinite variability and protective coating that masks it from antibodies, yet researchers have evidence from both human and animal studies suggesting that it may one day be possible to trigger an immune response that protects against infection.

In this article, Simon Noble, editor of IAVI Report, explores the prospects for a kind of HIV vaccine that aims to boost the immune response in people already infected with the virus, rather than what most vaccine researchers are working on, namely to protect against infection in the first place.

The article is written for scientifically educated readers who already have a basic knowledge about vaccines, and lay readers may therefoer find it somewhat technical. Nonetheless, it is a useful account of what many researchers feel is a worthwhile goal. The article reviews the different approaches in designing and testing therapeutic vaccines, and presents the views of different experts in the field.

It also features some of the scepticism around the concept of a therapeutic vaccine, including the concern that the immune system is so impaired by HIV infection, and the virus already so diverse after multiplying millions of times in the body, that it may not be possible to mount a stronger and more effective immune response against the virus.

This freely-available online medical textbook is written by expert clinicians in Europe and the United States in clear language that will have broad appeal to non-medical readers. Updated every year, it contains searchable information about the clinical manifestations of HIV/AIDS and its treatment, including acute infection, antiretroviral drugs, and drug resistance testing. Rather than going into detail about scientific or medical research, the textbook concentrates on the facts and explanations around HIV/AIDS signs and symptoms.

In this article, the coordinator of the WHO's HIV Vaccine Initiative, Jose Esparza, outlines the steps that need to be taken in order to develop a safe, effective and affordable preventive vaccine.

In addition to overcoming considerable scientific hurdles, the development of a successful vaccine will require that multiple clinical trials take place in parallel, in both developing and industrialised countries.

The article explains the nature of the three different levels of clinical trial that vaccines must undergo before they can be licensed for widespread use, and lists which countries have participated (up to 2001).

This is a comprehensive, technically detailed, review of the scientific advances in vaccine design over the past two decades. With more than 20 vaccines in pre-clinical testing and clinical trials, there is now hope that antibody-based immunity and cellular immunity are achievable goals.

Recent data, including investigation of people who have been exposed to HIV but remain uninfected, are helping to point the way forward. The authors warn, however, that the current crop of clinical trials are unlikely to reveal an effective vaccine, and that several large-scale phase III trials of different vaccine combinations will need to take place, which will require an unprecedented level of international cooperation. Additionally, the extent to which such vaccines can protect or control HIV infection and disease progression remains to be seen.

This feature article presents the progress and pitfalls made in HIV vaccine research up to May 2002 (before the company VaxGen announced the results of the first large-scale trial of an HIV vaccine in February 2003; as widely reported, and anticipated by this article, the VaxGen trial proved disappointing).

The article describes the scepticism some scientists had about the VaxGen vaccine design, and other strategies now underway.  But although many different vaccines are now in clinical trials, several hurdles remain, including a lack of understanding about what is needed in order to protect against infection, and the rapid mutation and 'escape' of the virus from immune attack. Also uncertain is the extent to which geographical variation in HIV strains – known as clades – are likely to help or hinder vaccine development.