• A good vaccine should induce neutralising antibody, helperT-cells and cytotoxic T-cells.
• Since antibodies bind to three dimensional structures,induction of neutralising antibody requires native envelope.Problem: Native envelope is trimeric.
• T-cells recognise 8–15 amino acid-long peptides bound toMajor Histocompatibility Complex (MHC) class I and IImolecules.Problem: Antigen needs to enter antigen presenting cells,usually dendritic cells, to be broken down to peptides.
• Peptides with novel adjuvants can generate good T-cellresponses.Problem: Different peptides bind to each MHC allele so alarge cocktail of different peptides may be needed.
• Adjuvants are needed to induce large responses.Problem: There are very few adjuvants available forunrestricted use in humans. Alum is mainly good for inductionof antibody responses.
• DNA immunisation can generate antibody, helper andcytotoxic responses and allows incorporation of adjuvantmolecules into the vaccine.Problem: So far DNA vaccination has not proved as effectivein man as in experimental animals.
• HIV is very variable and escape variants arise rapidly ininfected individuals. Prophylactic immunisation may tip thebalance in favour of the host and prevent escape. Some partsof the virus sequence are relatively invariant, these should betargeted if possible.
• In experimental animals immunisation with differentimmunogens appears promising. DNA vaccination followed byimmunisation with antigen in a recombinant viral vector seemsparticularly effective. This is now under trial in man.
