CHALLENGES IN DEVELOPING AND TESTING HIV/AIDS VACCINES IN AFRICA

INTRODUCTION

Five million people became infected with HIV worldwide and three million died in 2003 alone-the highest ever.1 Two thirds of all people with HIV/AIDS are in Africa. Sub-Saharan Africa is the region of the world that is most affected by HIV/AIDS. An estimated 26.6 million people are living with HIV/AIDS, and approximately 3.2 million new infections occurred in sub-Saharan Africa in 2003. In just the past year, the epidemic has claimed the lives of an estimated 2.3 million Africans. Ten million young people and almost three million children under 15 are living with HIV/AIDS. An estimated eleven million children have been orphaned by AIDS in subSaharan Africa.2

Although there have been more than 45 million cumulative HIV infections in Africa, there have been only two small phase 1 preventive HIV vaccine trials in the continent most severely affected by the pandemic.3 The first HIV vaccine trial in Africa of a product based on HIV strains from that continent began in Nairobi, Kenya in 2001. A collaborative group including Oxford University, UK, the University of Nairobi, Kenya, the Kenyan AIDS Vaccine Initiative (KAVI), and the International AIDS Vaccine Initiative (IAVI) developed DNA Vaccine and modified Vacina Ankara Vaccines on the basis of the gag gene of HIV-I subtype A and multiple cytotoxic Tlymphocyte epitopes, including some identified in studies of exposed uninfected Kenyan female sex workers.4 The second vaccine initiative was in South Africa, using Clade C, the most common subtype in the world.

Currently, nine approved vaccines are being tested world-wide, including six in Africa: one in Botswana, two in Kenya, two in South Africa and one in Uganda.5

Most HIV vaccine development and assessment has taken place in developed western countries. Early efforts to develop an HIV vaccine were based on the HIV-I subtype B strains prevalent in western nations, and most human clinical trials were done in the United States and Europe. Globally, there have been more than 80 Phase I and Phase II trials and only one product-a bivalent recombinant gp120 vaccine (AIDSVAX, VAXGEN Brisbane, CA, USA)-has reached large scale Phase III efficacy testing in North America, the Netherlands and Thailand.6

Studies of multiply exposed but uninfected individuals and long-term nonprogressors provide evidence that cellular responses can provide some protection against HIV/AIDS. Almost all humans develop some form of immune response to HIV infection. Particularly encouraging have been studies of several vaccine concepts tested against simian immunodeficiency virus (SIV), a virus similar to HIV that infects certain species of monkeys.7

A vaccine for Africa would be the best long-term preventive measure against the HIV/AIDS pandemic in the continent. Historically, vaccines have provided a safe, cost effective, and efficient means of preventing illness, disability and death from infectious diseases. Because there are many HIV-I subtypes, circulating recombinant forms, and intersubtype recombinant strains in the continent, and since the distribution of these subtypes will probably change overtime,8 an ideal HIV vaccine for Africa will be one that can protect against all genetically HIV-I strains (polyvalent HIV-I vaccine).

A vaccine is a drug that mimics a dangerous organism or pathogen, and creates immune system memory concerning that specific pathogen.9 A vaccine is antigenically similar to a pathogen or to its toxic by-products but has been treated so that it can be administered to people with little danger of disease. The vaccine sensitizes the immune system to the corresponding pathogen, inducing immunity without the danger of infectious disease developing during the lag period. In immunized people, natural exposure to the corresponding virulent pathogen triggers a protective anamnestic response that eradicates the pathogen or neutralizes toxins before symptoms of disease develop. An effective vaccine retains the corresponding pathogen's antigens but none of the pathogen's ability to damage the host. This is accomplished in a number of ways including the use of killed and attenuated organisms, purified antigen-fractions, toxoid, synthetic peptides and anti-idiotype antibodies.10

Vaccines are disease specific: A vaccine against polio protects only against polio and a vaccine against HIV infection protects only against HIV. In the case of a vaccine against viruses, this can either be an "inactivated" virus or an attenuated or mild form of a "live" virus.11

Inactivated vaccines are viruses that have lost their infectivity through damage to their nucleic acid by various agents such as formaldehyde or U. V. irradiation. These inactivating agents and treatments must be carefully selected and controlled so that they will not affect the antigenic specificity of the protein surface of the respective virus.

Live vaccines are virus strains that through passage of a typical host animal or cultured cells, have been made to mutate and have become "mild" or of low virulence, for the species to be vaccinated.