AIDSWEEKLY Plus; Monday, May 17, 1999
Daniel J. DeNoon, Senior Editor

A Dutch/Swedish/U.S. research team compared T-helper immune responses in groups of rhesus macaque monkeys given one of three different envelope-based HIV vaccines. The vaccines used the HIV-1[SF2] gp120 envelope glycoprotein expressed in vivo via DNA immunization (gene-gun administered); delivered as a subunit protein with MF59 adjuvant; or incorporated into ISCOMs.

"The best immune response to the gp120[SF2] antigen was obtained by incorporating this antigen into ISCOMs," reported Ernst. J. Verschoor of the Biomedical Primate Research Center, Rijswijk, Netherlands, and colleagues.

Verschoor et al. published their findings in the Journal of Virology "Comparison of Immunity Generated by Nucleic Acid- , MF59-, and ISCOM-Formulated Human Immunodeficiency Virus Type 1 Vaccines in Rhesus Macaques: Evidence for Viral Clearance," J Virol 1999 Apr;73(4):3292-300.

ISCOMs are cage-like structures made up of QuilA derivatives, cholesterol, and phospholipids. Antigens can be incorporated into these structures to improve immune recognition.

Verschoor et al. administered one of the three vaccines or a control vaccine to four groups of four monkeys:

• Four gene-gun immunizations with a plasmid expressing gp120,

• Three 50 (micro)g rgp120 immunizations with MF59 adjuvant,

• Three immunizations of 50 (micro)g rgp120 incorporated into ISCOMs, or

• A control group of two animals that received three immunizations with an irrelevant antigen and two animals that received DNA immunizations with an irrelevant DNA expression vector.

The gp120/DNA vaccine induced a weak type 1 T-helper response and low (if any) antibody responses. The rgp120/MF59 vaccine induced strong humoral responses. But the rgp120/ISCOM vaccine induced both types of responses.

Four weeks after the final immunization (week 40), all animals received an intravenous challenge with 50 50% monkey infectious doses of SHIV[SF13].

"The degrees of protection induced by each of these vaccine strategies were also clearly different," Verschoor et al. wrote. "All rgp120/DNA group animals became infected, while all rgp120/MF59 vaccinees exhibited evidence of transient infection. In contrast, two animals from the ISCOM group were fully protected while the remaining two animals had evidence of a transient infection that was successfully cleared."

The authors suggested that ISCOM-based vaccines could become a part of a multifaceted approach to an AIDS vaccine.

"The most effective prophylactic HIV-1 vaccines may be a combination of approaches with different vectors and/or subunits capable of inducing multiple effector mechanisms against a number of conserved viral antigens," they concluded.

This study was supported by both the EU Centralized Facility program for HIV-1 vaccine development and the EU MuNAvac project.

The corresponding author for this study is Jonathan L. Heeney, Department of Virology, Biomedical Primate Research Center, P.O. Box 3306, 2280 GH Rijswijk, Netherlands. Phone: 31 15 284 26 61. Fax: 31 15 284 39 86. Email: <heeney@bprc.nl>.

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