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Journal of Virology, April 1999, p. 3292-3300, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Comparison of Immunity Generated by Nucleic Acid-, MF59-, and ISCOM-Formulated Human Immunodeficiency Virus Type 1 Vaccines in Rhesus Macaques: Evidence for Viral Clearance

Ernst J. Verschoor,1 Petra Mooij,1 Herman Oostermeijer,1 Mike van der Kolk,1 Peter ten Haaft,1 Babs Verstrepen,1 Yide Sun,2 Bror Morein,3 Lennart Åkerblom,3 Deborah H. Fuller,4 Susan W. Barnett,2 and Jonathan L. Heeney1,*

Department of Virology, Biomedical Primate Research Center, Rijswijk, The Netherlands1; Chiron Corporation, Emeryville, California2; Department of Virology, The National Veterinary Institute, Uppsala, Sweden3; and PowderJect Vaccines, Inc., Madison, Wisconsin4

Received 13 July 1998/Accepted 5 January 1999

The kinetics of T-helper immune responses generated in 16 mature outbred rhesus monkeys (Macaca mulatta) within a 10-month period by three different human immunodeficiency virus type 1 (HIV-1) vaccine strategies were compared. Immune responses to monomeric recombinant gp120SF2 (rgp120) when the protein was expressed in vivo by DNA immunization or when it was delivered as a subunit protein vaccine formulated either with the MF59 adjuvant or by incorporation into immune-stimulating complexes (ISCOMs) were compared. Virus-neutralizing antibodies (NA) against HIV-1SF2 reached similar titers in the two rgp120SF2 protein-immunized groups, but the responses showed different kinetics, while NA were delayed and their levels were low in the DNA-immunized animals. Antigen-specific gamma interferon (IFN-gamma ) T-helper (type 1-like) responses were detected in the DNA-immunized group, but only after the fourth immunization, and the rgp120/MF59 group generated both IFN-gamma and interleukin-4 (IL-4) (type 2-like) responses that appeared after the third immunization. In contrast, rgp120/ISCOM-immunized animals rapidly developed marked IL-2, IFN-gamma (type 1-like), and IL-4 responses that peaked after the second immunization. To determine which type of immune responses correlated with protection from infection, all animals were challenged intravenously with 50 50% infective doses of a rhesus cell-propagated, in vivo-titrated stock of a chimeric simian immunodeficiency virus-HIVSF13 construct. Protection was observed in the two groups receiving the rgp120 subunit vaccines. Half of the animals in the ISCOM group were completely protected from infection. In other subunit vaccinees there was evidence by multiple assays that virus detected at 2 weeks postchallenge was effectively cleared. Early induction of potent type 1- as well as type 2-like T-helper responses induced the most-effective immunity.

* Corresponding author. Mailing address: Department of Virology, Biomedical Primate Research Center, P.O. Box 3306, 2280 GH Rijswijk, The Netherlands. Phone: 31 15 284 26 61. Fax: 31 15 284 39 86. E-mail: heeney{at}bprc.nl.

Journal of Virology, April 1999, p. 3292-3300, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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Copyright © 1999 by the American Society for Microbiology. All rights reserved.