AIDSWEEKLY Plus, 25 March 1996 issue; Published by Charles Henderson, Publisher. Editorial & Publishing Office: P.O. Box 5528, Atlanta, GA 30307-0528 / Telephone: (800) 633-4931; Subscription Office: P.O. Box 830409, Birmingham, AL 35283-0409 / FAX: (205) 995-1588
Daniel J. DeNoon, Senior Editor

Monkeys immunized via direct iliac lymph-node inoculation were protected against rectal challenge with simian immunodeficiency virus (SIV).

The findings provide insight into ways vaccines might be used to prevent the sexual transmission of HIV.

"No single immune response is protective," said researcher Thomas Lehner of Guys Hospital, London, England.

"We suggest that three successive immune barriers, from the epithelium, towards the iliac lymph nodes, and then the circulating immune cells and antibodies may each play a part in preventing viral transmission or decreasing the viral load."

Lehner reported the findings in a plenary address to the Eighth Annual Meeting of the National Cooperative Vaccine Development Groups for AIDS (NCVDG), held February 11-15, 1996, in Bethesda, Maryland.

In order to explore the best way to immunize people against mucosal exposure to HIV, Lehner and colleagues used the SIV/macaque model of HIV infection.

The researchers employed a vaccine comprised of two recombinant SIV antigens - the SIV gp120 envelope protein and the SIV p27 core protein - in alum.

The vaccine was administered via targeted iliac lymph nodes (TLN) in seven animals, intradermally in three animals, and nasally/rectally in three animals. Eight control monkeys were untreated.

All of the animals were then rectally challenged with free virus (the infectious J5 molecular clone of SIV[mac32H]).

Four of the seven TLN-inoculated animals resisted infection while only one of the untreated animals remained uninfected. The remaining three TLN-inoculated monkeys had reduced viral loads relative to the infected untreated animals.

None of the animals vaccinated by any other route resisted infection.

"By far the best antibody levels in rectal washings and urine were in the TLN-vaccinated animals," Lehner said. "But strong antibody responses were also seen in others: no single protective pattern emerged."

TLN vaccination elicited far better T-cell lymphoproliferative responses to SIV than vaccination via other routes.

Lehner also reported a preferential homing of SIV specific T cells and B cells to the rectum after TLN inoculation.

Early data show that compared to the TLN-inoculated animals that became infected, those that resisted infection had higher numbers of CD8 T cells.

CD8 T-cell-mediated suppression of HIV has been linked to the chemokines RANTES, MIP1(alpha), and MIP1(beta). Lehner and colleagues found that TLN-inoculated animals had significantly higher levels of these chemokines than did animals inoculated via other routes.

"Regional T- and B-cell responses can be elicited by targeted inoculation," Lehner said.

Copyright (c) 1995 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.

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Copyright © 1996 - Charles Henderson, Publisher. All rights Reserved. Permission to reproduce granted to AEGIS by Charles W. Henderson. Authorization to reproduce for personal use granted granted by C. W. Henderson, Publisher, provided that the fee of US$4.50 per copy, per page is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, Massachusetts 01970, USA.