The effect of route of immunization on mucosal immunity and protection

In macaques, the route of immunization has a profound effect on the immune response. Augmenting rectal or vaginal immunization with oral or nasal immunization enhanced the secretory IgA, serum IgG, and T cell responses. However, targeted iliac lymph node (TILN) immunization with recombinant simian immunode®ciency virus (SIV) gp120 and p27 elicited the most consistent mucosal antibody responses in the rectum, vagina, urine, seminal ¯uid, and blood. Both mucosal and TILN immunization induced speci®c CD4+ T cell proliferative responses in the iliac lymph nodes, which drain these mucosal surfaces, and in the splenic and circulating T cells. Rectal mucosal challenge with cell-free SIV induced total protection in 4 of 7 macaques that were immunized by the TILN route, and, compared with unimmunized macaques or those immunized by the mucosal route (), it induced a 190 % decreaseP!.001 in virus load in 3 of them. Protection from mucosal rectal infection with SIV was signi®cantly associated with an increase in the CD8 suppressor factor (which was generated by the iliac lymph node), RANTES, and MIP-1b ().P!.01 Oral immunization in rodents induced antibodies in the gen-ital tract and adoptively transferred murine mesenteric lymph node cells home to the genital tissues [1]. Direct administration of sheep red blood cells into Peyer's patches of Sprague-Dawley rats induced vaginal IgA and IgG antibodies [2]. These exper-iments suggest that sensitized B cells may home from GALT to the genital tract. However, oral immunization in nonhuman primates with the recombinant simian immunode®ciency virus (SIV) gag p27 fused to the yeast retrotransposon virus±like particles (p27:Ty-VLP) failed to induce signi®cant secretory IgA (s-IgA) antibodies in the genital or rectal tracts [3]. In a similar manner, microencapsulated formalin±treated SIV administered orally to rhesus macaques failed to elicit vaginal antibodies or protection when the animals were challenged with live SIV by the vaginal route [4]