GENETIC-CONTROL OF ANTIBODY-RESPONSES INDUCED AGAINST AN ANTIGEN DELIVERED BY RECOMBINANT ATTENUATED SALMONELLA-TYPHIMURIUM

Recombinant derivatives of nonpathogenic bacteria such as attenuated S almonella typhi have the potential to be used for delivery of heterolo gous antigens to the immune system. Genetic factors may modulate the i mmune responses to these live attenuated organisms and could therefore modify the immunogenicity of future human vaccines. In the present st udy, we compared the antibody responses of Ity or H-2 congenic strains of mice to a foreign antigen expressed by the murine attenuated aroA S. typhimurium strain. Our results demonstrate that the Ity gene may m odulate the antibody responses to the foreign antigen but that the maj or genetic influence is exerted by H-2 genes, which control the capaci ty of mice to respond to the antigen expressed by recombinant attenuat ed Salmonella cells. This genetic control is related to differences in responsiveness of different strains of mice to low doses of antigen. Increasing the amount of foreign antigen expressed by recombinant Salm onella cells overcame the genetic restriction of these responses. Thes e findings are potentially of great importance for the design of live vaccines for humans and show that care must be taken to optimize the a mount of foreign antigen delivered to the immune system.