However, against this pessimistic background, progress has been made and there remains hope that successful vaccines might yet be developed. Various strategies are being tried in an attempt to develop vaccines against HIV, varying among delivery of recombinant HIV proteins, plasmid DNA vaccination with HIV genes (see Section 1630), delivery of HIV genes in viral vectors, or combinations thereof. Many successful vaccines against other viral diseases contain a live attenuated strain of the virus, which raises an immune response but does not cause disease (see Section 1623). There are substantial difficulties in the development of live attenuated vaccines against HIV, not least the worry of recombination between vaccine strains and wildtype viruses that would lead to a reversion to virulence. An alternative approach is the use of other viruses, such as vaccinia or adenovirus, to deliver and express HIV genes that elicit Band Tcell responses against HIV antigens. Because these viral vectors have already demonstrated safety in other human vaccination studies, they have been obvious choices for initial trials. Recently, there has been encouraging, albeit limited, success with this type of approach in combination with boosts using recombinant gp120. Delivery of HIV gag, pol, and env genes via a canarypox viral vector followed by boosts with HIV gp120 was shown to reduce the risk of infection in a modest but significant number of highrisk vaccine recipients. This represents the first demonstration of any degree of efficacy in a large HIV vaccine trial to date. Perhaps as important, data from this study provided insights into the type of immune response that correlated with protection, indicating that the induction of non neutralizing antibodies that elicit ADCC (for example, IgG3 isotype) might provide protection. Because neutralizing antibodies against HIV have proven so difficult to elicit, this provides encouragement that they might not be required. Further, a study that used a cytomegalovirus (CMV) vector to deliver SIV genes to rhesus monkeys showed that potent CTL responses were induced. Although these CTL responses did not prevent infection by a pathogenic SIV strain, they did result in clearance of virus in about half of the monkeys vaccinated after its systemic spread. This unprecedented result suggests that the viral vector used for delivery of HIV genes—in this case a vector that produces HIV antigens for prolonged periods after vaccination—might play an important role in the type and amplitude of the antiviral CD8 Tcell response elicited, and protection might be achieved by an effective Tcell response alone. Additional studies will be needed to determine whether combination vaccines that elicit the appropriate non neutralizing antibodies and robust CD8 Tcell responses might achieve protection even in the absence of neutralizing antibodies.
In addition to the biological obstacles to developing effective HIV vaccines, there are difficult ethical issues. It would be unethical to conduct a vaccine trial without trying at the same time to minimize the exposure of a vaccinated population to the virus itself. The effectiveness of a vaccine can, however, only be assessed in a population in which the exposure rate to the virus is high enough to assess whether vaccination protects against infection. This means that initial vaccine trials might have to be conducted in countries where the incidence of infection is very high and public health measures have not yet succeeded in reducing the spread of HIV.
13-38 Prevention and education are important in controlling the spread of HIV and AIDS.