-"An HIV vaccine cannot consist of attenuated, actively replicating (live) HIV, due to possible reactivation.
-Killed whole virus (like the polio vaccine) might also be dangerous because one could not be sure one has killed all viral particles. A killed whole virus vaccine had also worked poorly in animal studies.
-There were successful vaccines that use subunits of viruses such as individual proteins: an example was the hepatitis B vaccine. However medical science was less experienced with them.
-There isno truly useful small animal model for studying HIV infectionand vaccines had to be developed in monkeys using SIV or the artificial monkey/human virus SHIV in monkeys, which did not have exactly the same immune effects as HIV.
-We do not know with certainty which immune response will provide protection; this is a major problem. Pre-efficacy studies of vaccines in monkeys and humans used correlates of immunogenicity such as CD8 cell response, but we do not know whether this immune response is in fact a correlate of efficacy.
-We have never before attempted to develop a vaccine against a retrovirus like HIV. Retroviruses, by integrating their genome into ours, are able to hide completely from immune surveillance within quiescent lymphocytes. This means that any vaccine has a small window of opportunity in which to prevent infection and would have to be extremely effective, repelling all attempts by HIV to attach to and infect host cells.
-HIV produces viral proteins such as tat and vif that actively interfere with what would otherwise be a potent anti-HIV response in both infected and uninfected cells.
-CD8 cellular vaccines do not block infection because they act at too late a stage, so, if they worked, would do so by reducing the viral load in chronic infection. They would not necessarily reduce the peak level of viraemia in the early burst of viral reproduction and might not control infections transmitted by people in acute infection.
-HIV is capable of developing immunity to the CD8 cellular response"
