Immunization, Vaccines and Biologicals



According to the 2007 WHO/UNAIDS estimates, at the end of 2007, 33.2 million people were living with HIV. Some 2,5 million people became newly infected that year and 2.1 million died of AIDS, which maintains AIDS as a leading cause of death in Africa.

More than 95% of HIV infections are in developing countries, two-thirds of them in sub-Saharan Africa, where over 28 million people are living with HIV. While infection rates are lower in Asia and the Pacific, where over 7 million are infected, there is a risk that localized epidemics involving mainly high-risk groups could spark off major epidemics in some of the world’s most populous countries.

The disease is having a major impact on social and economic development. Poverty is increasing in many countries as households lose one or more breadwinners to AIDS. And both public services and private companies are reeling from the impact of HIV-related sickness and deaths among their workforce.

In June 2001, the United Nations General Assembly declared HIV/AIDS to be “a global emergency.” Member States agreed to meet new targets for HIV prevention and care. These included a 25% reduction in infection rates among 15–24 year olds in the worst-affected countries by 2005 (and globally by 2010) and a 20% reduction in the number of infants infected with HIV by 2005 (and by 50% by 2010). UNAIDS and co-sponsors/partners have urged countries to implement a comprehensive package of strategies for prevention and care, including:

  • access to affordable condoms
  • prompt treatment of other sexually transmitted infections (which increase the risk of infection with HIV)
  • access to voluntary HIV testing and counselling
  • prevention of mother-to-child transmission
  • promotion of advice and support to reduce HIV infection among intravenous drug users
  • sexual health education in schools and the community
  • improved access to care, support and treatment, including sustainable access to affordable supplies of medicines and diagnostics.

While effective HIV care and prevention strategies, together with strong political commitment, have helped reverse the tide of HIV in some countries – notably Senegal, Thailand and Uganda – a vaccine is also needed to complement existing strategies.

Vaccine update While much more basic research is still needed, a successful vaccine against HIV is believed to be scientifically feasible (see Box page 59). However, this optimism is tempered by continued under-investment in HIV vaccine development. It is estimated that approximately US$ 600 million a year is invested in HIV vaccine R&D, the majority from the US National Institutes of Health. But not enough is being spent to develop candidate vaccines based on HIV subtypes circulating in developing countries, or to strengthen vaccine evaluation sites in these countries where 95% of infections and most deaths occur.

There are at least nine HIV-1 genetic subtypes circulating in the world. Most research to date has focused on a vaccine for HIV subtype (or clade) B, which is the main subtype in the Americas, Australia, Japan and western Europe. The subtypes mainly found in sub-Saharan Africa and Asia – where the epidemic has hit hardest – are A, C, D and E and there is no assurance that a vaccine based on subtype B will be effective against these others. In addition, vaccine efficacy may vary in different populations because of genetic make-up.

The first Phase I trial of an HIV candidate vaccine was carried out in the United States in 1987. Since then, more than 30 different candidate vaccines, developed by different companies and using different technologies, have been tested in 80 Phase I and II trials – mainly in the United States and Europe, although more recently also in developing countries (Brazil, China, Cuba, Haiti, Kenya, Peru, Thailand, Trinidad and Uganda).

Today, 19 HIV candidate vaccines are at different levels of clinical testing in Europe, the United States and elsewhere. The first large-scale Phase III human trials of HIV vaccines are under way in the United States and Thailand. These involve 5400 volunteers in the United States, with sites in Canada and the Netherlands, and 2500 volunteers in Thailand. The trials involve the use of candidate vaccines based on gp120 (the envelope protein of HIV) corresponding to the virus types most commonly found in Europe and North America (B) and Thailand (E). Definitive results from the North American trial are xpected to be available at the beginning of 2003, with results from the Thai trial a year later. While these initial trials may not result in the ideal vaccine, they may help advance the science and provide valuable information for future research efforts.

The next Phase III trial, using a prime-boost combination – a anarypox-HIV recombinant vector followed by gp120 – is due to start in Thailand at the end of 2002 or beginning of 2003. Other novel candidate vaccines are being developed in the laboratory and undergoing initial Phase I/II human trials and it is expected that the best products will move to additional Phase III trials in the next 3-4 years.

In the meantime, WHO and UNAIDS are working to facilitate trials in African countries through the African AIDS Vaccine Programme (AAVP), an initiative adopted in 2001 by African Heads of State at the African Summit on HIV/AIDS, Tuberculosis and Malaria in Abuja, Nigeria. The AAVP has launched an appeal for US$ 233 million for the next seven years, to help accelerate the development and testing of a vaccine for use in Africa. Some of the funds will be used to strengthen the capacity of African research centres to conduct clinical trials of vaccine candidates.

The major manufacturers committed to HIV/AIDS vaccine R&D are Aventis Pasteur, GlaxoSmithKline, Merck & Co, and Wyeth-Lederle. Another company, VaxGen has moved products to two large-scale Phase III trials in North America and Thailand. Activities involving HIV/AIDS vaccine R&D are also supported by WHO/UNAIDS, the European Commission, United States government agencies, the UK Medical Research Council, the French Agency for Research on AIDS and the IAVI, among others. IAVI has spearheaded several projects aimed at exploring new vaccine concepts, with a focus on candidate vaccines based on HIV-1 strains prevalent in developing countries.