• A good vaccine should induce neutralising antibody, helper
T-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 to Major Histocompatibility Complex (MHC) class I and II molecules.
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-cell responses.
Problem: Different peptides bind to each MHC allele so a large cocktail of different peptides may be needed.
• Adjuvants are needed to induce large responses.
Problem: There are very few adjuvants available for unrestricted use in humans. Alum is mainly good for induction of antibody responses.
• DNA immunisation can generate antibody, helper and cytotoxic responses and allows incorporation of adjuvant molecules into the vaccine. Problem: So far DNA vaccination has not proved as effective in man as in experimental animals.
• HIV is very variable and escape variants arise rapidly in infected individuals. Prophylactic immunisation may tip the balance in favour of the host and prevent escape. Some parts of the virus sequence are relatively invariant, these should be targeted if possible.
• In experimental animals immunisation with different immunogens appears promising. DNA vaccination followed by immunisation with antigen in a recombinant viral vector seems particularly effective. This is now under trial in man.
• 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 to Major Histocompatibility Complex (MHC) class I and II molecules.
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-cell responses.
Problem: Different peptides bind to each MHC allele so a large cocktail of different peptides may be needed.
• Adjuvants are needed to induce large responses.
Problem: There are very few adjuvants available for unrestricted use in humans. Alum is mainly good for induction of antibody responses.
• DNA immunisation can generate antibody, helper and cytotoxic responses and allows incorporation of adjuvant molecules into the vaccine. Problem: So far DNA vaccination has not proved as effective in man as in experimental animals.
• HIV is very variable and escape variants arise rapidly in infected individuals. Prophylactic immunisation may tip the balance in favour of the host and prevent escape. Some parts of the virus sequence are relatively invariant, these should be targeted if possible.
• In experimental animals immunisation with different immunogens appears promising. DNA vaccination followed by immunisation with antigen in a recombinant viral vector seems particularly effective. This is now under trial in man.
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