IMMUNIZATION OF MACACA-MULATTA WITH AROA ATTENUATED SALMONELLA-TYPHIMURIUM EXPRESSING THE SIVP27 ANTIGEN

Attenuated bacteria expressing foreign antigens stimulate both systemi c and mucosal immune responses to the recombinant protein. We studied the infection of rhesus macaques with an attenuated Salmonella typhimu rium expressing the simian immunodeficiency virus p27 capsid protein. Juvenile rhesus macaques were inoculated by intragastric intubation wi th doses ranging from 3 to 9 x 10(9) viable aroA attenuated S. typhimu rium. The bacterial infection was self-limiting with no overt clinical signs. Salmonella were shed in the feces of macaques for approximatel y five days. Salmonella were isolated from fecal material to examine t he in vivo stability of both the attenuating mutation and the integrat ed SIVp27 expression cassette. All Salmonella isolates retained both t he attenuating mutation and the recombinant expression construct. In v itro analysis showed that a minimum of 7.2 mu g of p27 was delivered b y a single oral dose with attenuated, recombinant S. typhimurium.