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Journal of Virology, January 2000, p. 371-378, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Vaccination of Macaques against Pathogenic Simian Immunodeficiency Virus with Venezuelan Equine Encephalitis Virus Replicon Particles

Nancy L. Davis,1,* Ian J. Caley,1 Kevin W. Brown,1 Michael R. Betts,1,dagger David M. Irlbeck,1 Kathryn M. McGrath,2 Mary J. Connell,3 David C. Montefiori,4 Jeffrey A. Frelinger,1 Ronald Swanstrom,1,5 Philip R. Johnson,3 and Robert E. Johnston1

Department of Microbiology and Immunology,1 Curriculum in Genetics and Molecular Biology,2 and University of North Carolina Center for AIDS Research5, University of North Carolina, Chapel Hill, North Carolina 27599; Children's Hospital and Department of Medical Microbiology and Immunology, The Ohio State University, Columbus, Ohio 432053; and Department of Surgery, Duke University Medical Center, Durham, North Carolina 277104

Received 1 July 1999/Accepted 1 October 1999

Vaccine vectors derived from Venezuelan equine encephalitis virus (VEE) that expressed simian immunodeficiency virus (SIV) immunogens were tested in rhesus macaques as part of the effort to design a safe and effective vaccine for human immunodeficiency virus. Immunization with VEE replicon particles induced both humoral and cellular immune responses. Four of four vaccinated animals were protected against disease for at least 16 months following intravenous challenge with a pathogenic SIV swarm, while two of four controls required euthanasia at 10 and 11 weeks. Vaccination reduced the mean peak viral load 100-fold. The plasma viral load was reduced to below the limit of detection (1,500 genome copies/ml) in one vaccinated animal between 6 and 16 weeks postchallenge and in another from week 6 through the last sampling time (40 weeks postchallenge). The extent of reduction in challenge virus replication was directly correlated with the strength of the immune response induced by the vectors, which suggests that vaccination was effective.

* Corresponding author. Mailing address: Department of Microbiology and Immunology, CB 7290, University of North Carolina, Chapel Hill, NC 27599. Phone: (919) 966-4026. Fax: (919) 962-8103. E-mail: joiner{at}med.unc.edu.

dagger Present address: Division of Infectious Disease, University of Texas---Southwestern, Dallas, TX 75235-9113.

Journal of Virology, January 2000, p. 371-378, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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