 Vaccination is one of the most important achievements of medicine. Injection of modified germs, or materials from them, induces protective immunity against the infections which they cause. Successful immunisation induces a protective immune response against particular components of the target germ, the so-called immunogens. For some diseases the immunogens are not known and for others they are difficult and expensive to produce, transport and administer, for example influenza vaccine must be produced in millions of chicken eggs. A very attractive potential solution is to inject the deoxyribose nucleic acid DNA gene encoding the immunogen rather than the immunogen itself. In this process, known as DNA vaccination, the DNA enters cells, predominantly at the site of injection, and causes them to produce the immunogen locally within the body. DNA vaccination works well and stimulates excellent protective immunity against a variety of different infections, and even some cancers, in mice, horses, dogs, rabbits and pigs. But in humans and other primates, and in cows and sheep, the immune response to DNA vaccination is very feeble. Despite enormous academic and pharmaceutical industry efforts, the reasons for this failure have not been understood or overcome. The investigators previously discovered that a protein in human blood, known as serum amyloid P component SAP, is the only normal blood protein which binds strongly to DNA. The investigators have now found that, in each of the animal species in which DNA vaccination is effective, this protein is either absent or, if it is present, it binds only weakly to DNA. In contrast, nonhuman primates, cows and sheep share with humans the presence of SAP proteins which strongly bind to DNA. The investigators believe that binding of DNA by SAP may be responsible for blocking induction of immune responses by DNA and that removal of SAP may overcome this inhibition. SAP contributes to important human diseases, amyloidosis and Alzheimers disease, and the investigators have previously developed a drug, R-1-6-R-2-carboxy-pyrrolidin-1-yl-6-oxohexanoylpyrrolidine-2-carboxylic acid CPHPC, which safely removes almost all SAP from the blood in humans. Another laboratory has recently reported that the presence of human SAP inhibits DNA vaccination in mice and that this effect is reversed by the investigators drug, CPHPC. These observations confirm the investigators hypothesis. The investigators now propose to undertake the first human clinical study of DNA vaccination after SAP depletion. The investigators will measure the immune responses to human immunodeficiency virus HIV-1 DNA vaccination in 40 healthy adult men, comparing a group in whom SAP has been completely depleted at the time of DNA vaccination and a control group vaccinated without SAP depletion. The investigators predict that SAP depletion at the time of DNA vaccination will enhance the immune response. 