Development of an AIDS vaccine candidate: recombinant BCG vaccine vehicles induce humoral and cell-mediated immune responses to HIV antigens.
Int Conf AIDS 1991 Jun 16-21; 7:38 (abstract no. M.A.64) Aldovini A, Young R; Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA USA
We have used the potent immunological properties of the human tuberculosis vaccine Mycobacterium bovis BCG to develop a live recombinant vaccine vehicle that can produce selected pathogen proteins and stimulate the mammalian immune system to respond to them. BCG has a number of features that make it a particularly attractive live recombinant vaccine vehicle: BCG and other mycobacteria are highly effective adjuvants, BCG has a long record of safe use in man, it is one of the few vaccines that can be given at birth, it engenders long-lived immune responses with only a single dose, and there is a worldwide distribution network with experience in BCG vaccination. Genes encoding HIV1 gag, pol, and env precursor proteins were placed under the control of the mycobacterial hsp70 promoter and ribosome binding site and were introduced into BCG on autonomously replicating plasmids. In the recombinant bacteria, the HIV1 proteins accounted for up to 0.1% of total protein. When injected into mice, recombinant BCG expressing HIV gag stimulated both humoral and cell-mediated immune responses to the viral protein. These results demonstrate that HIV1 structural proteins can be expressed in BCG recombinants and that these foreign polypeptides can be immunogenic. Features of this vehicle may be of particular importance for inducing strong and persistent immune responses against HIV1.
Keywords: AEGIS, AIDS Vaccines, Vaccines, Synthetic, Mycobacterium bovis, HIV Antigens, Gene Products, env, Vaccines, Attenuated, Viral Proteins, Vehicles, Human, Male, Animal, Mice, ICA7 910616
MA64
