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Journal of Virology, October 2005, p. 12264-12272, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12264-12272.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CD8+ Lymphocytes Do Not Mediate Protection against Acute Superinfection 20 Days after Vaccination with a Live Attenuated Simian Immunodeficiency Virus

Richard Stebbings,1* Neil Berry,2 Herman Waldmann,4 Pru Bird,5 Geoff Hale,5 Jim Stott,2 David North,3 Robin Hull,3 Joanna Hall,2 Jenny Lines,1 Stuart Brown,2 Nikki D'Arcy,2,{dagger} Leanne Davis,2 William Elsley,2 Cherry Edwards,1 Deborah Ferguson,2 Jane Allen,2,{ddagger} and Neil Almond2

Division of Immunology,1 Division of Retrovirology,2 Division of Virology, National Institute for Biological Standards and Control, Potters Bar, United Kingdom,3 Sir William Dunn School of Pathology,4 Oxford Therapeutic Antibody Centre, Oxford University, Oxford, United Kingdom5

Received 24 March 2005/ Accepted 3 July 2005

In order to test the hypothesis that CD8+ cytotoxic T lymphocytes mediate protection against acute superinfection, we depleted >99% of CD8+ lymphocytes in live attenuated simian immunodeficiency virus macC8 (SIVmacC8) vaccinees from the onset of vaccination, maintained that depletion for 20 days, and then challenged with pathogenic, wild-type SIVmacJ5. Vaccinees received 5 mg per kg of humanized anti-CD8 monoclonal antibody (MAb) 1 h before inoculation, followed by the same dose again on days 3, 7, 10, 13, and 17. On day 13, peripheral CD8+ T lymphocytes were >99% depleted in three out of four anti-CD8 MAb-treated vaccinees. At this time attenuated SIVmacC8 viral RNA loads in anti-CD8 MAb-treated vaccinees were significantly higher than control vaccinees treated contemporaneously with nonspecific human immunoglobulin. Lymphoid tissue CD8+ T lymphocyte depletion was >99% in three out of four anti-CD8 MAb-treated vaccinees on the day of wild-type SIVmacJ5 challenge. All four control vaccinees and three out of four anti-CD8 MAb-treated vaccinees were protected against detectable superinfection with wild-type SIVmacJ5. Although superinfection with wild-type SIVmacJ5 was detected at postmortem in a single anti-CD8 MAb-treated vaccinee, this did not correlate with the degree of preceding CD8+ T lymphocyte depletion. Clearance of attenuated SIVmacC8 viremia coincided with recovery of normal CD8+ T lymphocyte counts between days 48 and 76. These results support the view that cytotoxic T lymphocytes are important for host-mediated control of SIV primary viremia but do not indicate a central role in protection against acute superinfection conferred by inoculation with live attenuated SIV.

* Corresponding author. Mailing address: Division of Immunology, NIBSC, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG, United Kingdom. Phone: 44 1707 641278. Fax: 44 1707 650223. E-mail: rstebbings{at}nibsc.ac.uk.

{dagger} Present address: Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

{ddagger} Deceased.

Journal of Virology, October 2005, p. 12264-12272, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12264-12272.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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