title: Effective vaccination against long-term gammaherpesvirus latency.
abstract: The fundamental question of whether a primed immune system is capable of preventing latent gammaherpesvirus infection remains unanswered. Recent studies showing that vaccination can reduce acute replication and short-term latency but cannot alter long-term latency further call into question the possibility of achieving sterilizing immunity against gammaherpesviruses. Using the murine gammaherpesvirus 68 (gammaHV68) system, we demonstrate that it is possible to effectively vaccinate against long-term latency. By immunizing mice with a gammaHV68 mutant virus that is deficient in its ability to reactivate from latency, we reduced latent infection of wild-type challenge virus to a level below the limit of detection. Establishment of latency was inhibited by vaccination regardless of whether mice were challenged intraperitoneally or intranasally. Passive transfer of antibody from vaccinated mice could partially reconstitute the effect, demonstrating that antibody is an important component of vaccination. These results demonstrate the potential of a memory immune response against gammaherpesviruses to alter long-term latency and suggest that limiting long-term latent infection in a clinically relevant situation is an attainable goal.
authors.affiliation: Department of Pathology & Immunology and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tibbetts
authors.forename: J Scott
authors.initials: JS
authors.lastname: McClellan
authors.forename: Shivaprakash
authors.initials: S
authors.lastname: Gangappa
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Speck
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000818:Animals; D018142:Gammaherpesvirinae / Q000235:genetics / Q000276:immunology*; D006566:Herpesviridae Infections / Q000517:prevention & control* / Q000821:virology; D022283:Herpesvirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014611:Vaccination; D014775:Virus Activation / Q000235:genetics; D017735:Virus Latency / Q000276:immunology*
chemical_list: D022283:Herpesvirus Vaccines