The Effect of Route of Immunization on Mucosal Immunity and Protection

Abstract

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 immunodeficiency virus (SIV) gp120 and p27 elicited the most consistent mucosal antibody responses in the rectum, vagina, urine, seminal fluid, and blood. Both mucosal and TILN immunization induced specific 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 (P<.001), it induced a >90% decrease in virus load in 3 of them. Protection from mucosal rectal infection with SIV was significantly associated with an increase in the CD8 suppressor factor (which was generated by the iliac lymph node), RANTES, and MIP-1beta (P<.01).

Simian-Human Immunodeficiency Virus SHIV89.6-Induced Protection against Intravaginal Challenge with Pathogenic SIVmac239 Is Independent of the Route of Immunization and Is Associated with a Combination of Cytotoxic T-Lymphocyte and Alpha Interferon Responses

“…It has been suggested that an HIV vaccine needs to elicit genital immune responses to effectively prevent heterosexual transmission (40,42,58,59). Thus, the first goal of the present study was to directly compare the effect of the route of immunization on i.vag.…”

Cervicovaginal Lamina Propria Lymphocytes: Phenotypic Characterization and Their Importance in Cytotoxic T-Lymphocyte Responses to Simian Immunodeficiency Virus SIVmac251

“…The finding of a high frequency of virus-specific CD8 ϩ T cells in the cervicovaginal compartment, coupled with the notion that mucosal immunization may provide better protection against mucosal challenge than systemic immunization (3,4,30,31), has important implications for the development of vaccine modalities (57) that can target mucosal sites in order to prevent HIV-1 infection.…”

Correlation betweenenvV1/V2 Region Diversification and Neutralizing Antibodies during Primary Infection by Simian Immunodeficiency Virus sm in Rhesus Macaques

“…Virus variants that develop after infection are commonly characterized by sequence changes, length changes, and changes in the carbohydrate composition of the V1/V2, namely alterations in N-linked and O-linked glycosylation sites (1,7,53,55). In addition, the route of exposure to antigen in vaccine presentation, and potentially in infection, can affect the nature of the immune response (26,57).The analysis of env heterogeneity has yielded and will continue to yield important information about the biology of the viral Env protein. We have focused on the heterogeneity of the V1/V2 variable region to track changes in env gene populations, although other regions of env are amenable to similar analysis.…”

“…Virus variants that develop after infection are commonly characterized by sequence changes, length changes, and changes in the carbohydrate composition of the V1/V2, namely alterations in N-linked and O-linked glycosylation sites (1,7,53,55). In addition, the route of exposure to antigen in vaccine presentation, and potentially in infection, can affect the nature of the immune response (26,57).…”