Development of an AIDS vaccine

The viral surface protein, gp 120, is capable of binding to a specific site on the CD4 molecule, found on the surface of susceptible cells (Table 13.10). Some CD4 negative cells may (rarely) also become infected, indicating the existence of an entry mechanism independent of CD4. 

Infection of CD4+ cells commences via interaction between gp 120 and the CD4 glycoprotein, which effectively acts as the viral receptor. Entry of the virus into the cell, which appears to require some additional cellular components, occurs via endocytosis and/or fusion of the viral and cellular membranes. The gp 41 transmembrane protein plays an essential role in this process. 

After this initial phase of infection subsides, the free viral load in the blood declines, often to almost undetectable levels. This latent phase may last for anything up to 10 years or more. During this phase, however, there does seem to be continuous synthesis and destruction of viral particles. This is accompanied by a high turnover rate of (CD4+) T-helper lymphocytes. The levels of these T-lymphocytes decline with time, as does antibody levels specific for viral proteins. The circulating viral load often increases as a result, and the depletion of T-helper cells compromises general immune function. As the immune system fails, classical symptoms of AIDS-related complex (ARC) and, finally, full-blown AIDS begin to develop. 

In excess of 40 million individuals are now thought to be infected by HIV. In 2001 alone, it was estimated that 3 million people died from AIDS and a further 5 million became infected with the virus. Over 20 million people in total are now thought to have died from AIDS. The worst affected geographical region is the southern half of Africa (Table 13.11). Some 90 per cent of sufferers live in poorer world regions. So far, no effective therapy has been discovered, and the main hope of eradicating this disease lies with the development of safe, effective vaccines. The first such putative vaccine entered clinical trials in 1987 but, thus far, no effective vaccine has been developed. 

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An HIV vaccine has not yet been successfully developed and approved for use in the United States. As indicated earlier, vaccines are typically an altered form of the original virus that is administered to stimulate the immune system, so that the immune system can recognize and destroy the virus if a person is exposed to it. Creation of an HIV vaccine is understandably a complicated endeavor, given the complexity of this virus and its tendency to evolve and mutate into different types of HIV.78,108 Nonetheless, the development of a safe, effective vaccine remains the best pharmacologic method for dealing with the spread of the virus, especially in underdeveloped nations that continue to experience a rise in the incidence of HIV and AIDS.15,48... 

The development of an effective AIDS vaccine is difficult owing to the antigenic diversity of HIV strains. Because... 

The development of an effective AIDS vaccine is difficult owing to the antigenic diversity of HIV strains. Because its mechanism for replication is quite error prone, a population of HI V presents an ever-changing array of coat proteins. Indeed, the mutation rate of HIV is more than 65 times higher than that of influenza virus. A few broadly neutralizing antibodies have been isolated from asymptomatic, HIV infected persons. Several of these antibodies show an unusual form, described in Section 33.3, that allows them to bind many types of HIV. 

The concept of pleomorphism may very well tie in with the fact that nearly 600 different kinds of cancer cells reportedly have been identified. And that one kind of cancer may lead to another, or secondary, cancer. That is, cancer may not only metastasize or spread as the same kind of cancer, but a new kind may occur (that is, in different kinds of cells). If, say, viruses are involved in cancer formation, and can change from one kind to another, then the different kinds of cancer-causing viruses could be legion. And this, of course, may be an obstruction to the development of a general vaccine, as is in the case of AIDS. (It may be reemphasized that the work of Dr. Livingston was aimed at autogenous vaccines, specific to the particular patient.)... 

In the future edible vaccines may be produced in plants. Nevertheless, it is often very difficult to devise effective vaccines. In spite of 80 years of effort better vaccines against tuberculosis are needed. All efforts to produce an AIDS vaccine have failed. A satisfactory vaccine must achvate both B cells and T cells. Activation of the latter may be especially difficult. Continuous development of new strains of bacteria is a problem for vaccinahon against... 

A number of approaches are being assessed with regard to developing an effective AIDS vaccine. No safe attenuated form of the virus has been recognized to date, nor is one likely to be developed in the foreseeable future. The high level of mutation associated with HIV would, in any case, heighten fears that spontaneous reversion of any such product to virulence would be possible. 

The single most important issue in developed countries is the safety of a vaccine, a single death in a million vaccinations for a new vaccine would be unacceptable (except possibly if it were an effective AIDS vaccine). While this is obviously important in a Third World country, other issues such as cost and how to deliver the vaccine are of paramount importance. 

Two major diseases, malaria and AIDS, are still out of control vaccines are not available, while the malaria parasite and the HIV virus, responsible for AIDS, have developed resistance to current dmgs. Variability of the agent, lack of commercial interest, and perhaps also unconfessed political plans at population growth control, have been an obstacle to active immunization against malaria. The hope for an HIV vaccine is now from the engagement of Merck Co (Conference 2001). 

Although vaccines exist for many serious viral infections, some drawbacks still exist. Some vaccines are only partially effective, and viral infection still occurs in a significant percentage of vaccinated individuals. Other vaccines, especially killed vaccines, often require periodic readministration (boosters) to help maintain antiviral immunity. In addition, certain types of viruses still lack an effective vaccination. For example, no vaccine is currently approved for the HIV that causes AIDS.51,98 Hence, the improvement of existing vaccines and the development of new vaccines remain two of the more important aspects of antiviral chemotherapy.4... 

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