Immunization of Newborn Rhesus Macaques with Simian Immunodeficiency Virus (SIV) Vaccines Prolongs Survival after Oral Challenge with Virulent SIVmac251

http://jvi.asm.org/cgi/content/abstract/77/1/179

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Immunization of Newborn Rhesus Macaques with Simian Immunodeficiency Virus (SIV) Vaccines Prolongs Survival after Oral Challenge with Virulent SIVmac251

Koen K. A. Van Rompay,¹ Jennifer L. Greenier,¹ Kelly Stefano Cole,² Patricia Earl,³ Bernard Moss,³ Jonathan D. Steckbeck,² Bapi Pahar,¹ Tracy Rourke,¹ Ronald C. Montelaro,² Don R. Canfield,¹ Ross P. Tarara,¹ Christopher Miller,^1,4 Michael B. McChesney,¹ and Marta L. Marthas^1,4*

California National Primate Research Center,¹ Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, California,⁴ Laboratory of Viral Diseases, National Institutes of Health, Bethesda, Maryland,³ Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania²

Received 22 July 2002/ Accepted 30 September 2002

There is an urgent need for active immunization strategies that,if administered shortly after birth, could protect infants in developing countries from acquiring human immunodeficiency virus (HIV) infection through breast-feeding. Better knowledge ofthe immunogenic properties of vaccine candidates in infantsand of the effect of maternal antibodies on vaccine efficacywill aid in the development of such a neonatal HIV vaccine.Simian immunodeficiency virus (SIV) infection of infant macaquesis a useful animal model of pediatric HIV infection with whichto address these questions. Groups of infant macaques were immunizedat birth and 3 weeks of age with either modified vaccinia virusAnkara (MVA) expressing SIV Gag, Pol, and Env (MVA-SIVgpe) orlive-attenuated SIVmac1A11. One MVA-SIVgpe-immunized group hadmaternally derived anti-SIV antibodies prior to immunization.Animals were challenged orally at 4 weeks of age with a geneticallyheterogeneous stock of virulent SIVmac251. Although all animalsbecame infected, the immunized animals mounted better antiviralantibody responses, controlled virus levels more effectively,and had a longer disease-free survival than the unvaccinatedinfected monkeys. Maternal antibodies did not significantlyreduce the efficacy of the MVA-SIVgpe vaccine. In conclusion,although the tested vaccines delayed the onset of AIDS, furtherstudies are warranted to determine whether a vaccine that elicitsstronger early immune responses at the time of virus exposuremay be able to prevent viral infection or AIDS in infants.

* Corresponding author. Mailing address: California National Primate Research Center, University of California at Davis, Davis, CA 95616. Phone: (530) 752-0447. Fax: (530) 752-2880. E-mail: mlmarthas@ucdavis.edu.

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