Generation of CD8 + T Cell-Generated Suppressor Factor and beta -Chemokines by Targeted Iliac Lymph Node Immunization in Rhesus Monkeys Challenged with SHIV-89.6P by the Rectal Route

Abstract

The targeted lymph node (TLN) immunization strategy was investigated in macaques, in order to determine the efficacy in generating secretory, systemic, and cellular immune responses, CD8⁺ T cell-generated suppressor factors, and beta-chemokines. TLN immunization of the rectal and genital mucosa-associated iliac lymph nodes (TILNs) was compared with axillary TLN immunization (TAxLN) using HIV-1 M N/LAI gp140^env and SIV p27^gag in alum. Significantly higher immune responses, as well as CD8⁺ T cell-generated anti-SIV factors and the beta-chemokines RANTES, MIP-1 alpha, and M IP-1 beta, were elicited by iliac as compared with axillary TLN immunization. The immune responses induced by TLN immunization were examined for their capacity to prevent rectal mucosal infection by the pathogenic dual-tropic SHIV-89.6P. Despite significant secretory, serum, cellular, and beta -chemokine responses, the macaques were infected by SHIV-89.6P. Whether the lack of protection was associated with the antigenic unrelatedness of SHIV-89.6P to the immunizing HIV-1 MN/LAI gp140 or to the virus utilizing CXCR4 to a much greater extent than CCR5, remains to be determined.