Immunization of Macaca mulatta with aroA attenuated Salmonella typhimurium expressing the SIVp27 antigen

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