No abstract

The need for an effective vaccine against HIV has prompted a refocusing of attention on mucosal immunity. More than 75% of all infections are acquired across a mucosal surface. It is therefore a prerequisite for a vaccine to target directly the mucosal tissues or indirectly the regional lymph nodes in order to prevent or control viral replication. Although mucosal immunization has induced responses at the genital or rectal surfaces, immune mechanisms alone have not been shown to be sufficient to contain infections in macaques. A growing body of evidence suggests that a dual mechanism may be required for effective mucosal protection, mediated by specific CD4 and CD8 T cell and antibody responses to the immunizing agents, plus innate antiviral factors and beta chemokines that down-regulate CCR5 coreceptors. Targeted iliac lymph node immunization with SIV gp 120 and p27 in alum prevents SIV infection or significantly decreases the viral load when immunized macaques were challenged with SIV by the rectal route. Indeed, in addition to specific immunity, including significant SIgA antibody secreting cells in the iliac lymph nodes, CD8-suppressor factor and the 3beta chemokines (RANTES, MIP-1alpha and MIP-1beta) are significantly associated with protection against rectal mucosal SIV infection.

Native horseradish peroxidase (HRP) is known to pass rapidly through glomeruli when injected into rats. We have found that a conjugate of HRP with poly-lysine is readily endocytosed by glomerular epithelial cells (GEC). We have used this conjugate to study the GEC endocytotic process in male Wistar rats. The conjugate has an approximate molecular weight of 55-58,000, a pI of greater than 10.0, and almost the same secondary conformation as HRP; it does not increase urinary protein excretion significantly or alter the morphology of the renal glomeruli. After intravenous injection of the conjugate, it could be found in the GBM from 1 min to 4 h. At 1 min, it was evenly distributed on GEC foot processes and plasma membrane. GEC start to take up the conjugate from 1 min post-injection, by cellular membrane invagination. This reached a maximum at 4 h. Some of the endocytosed conjugate passed to lysosomes from the endosomal system. The amount of peroxidase demonstrable in the glomerular epithelial cells was considerably reduced by 24 h.