title: Early potent protection against heterologous SIVsmE660 challenge following live attenuated SIV vaccination in Mauritian cynomolgus macaques.
abstract: BACKGROUND
  Live attenuated simian immunodeficiency virus (SIV) vaccines represent the most effective means of vaccinating macaques against pathogenic SIV challenge. However, thus far, protection has been demonstrated to be more effective against homologous than heterologous strains. Immune correlates of vaccine-induced protection have also been difficult to identify, particularly those measurable in the peripheral circulation.
  
  
  RESULTS
  Here we describe potent protection in 6 out of 8 Mauritian-derived cynomolgus macaques (MCM) against heterologous virus challenge with the pathogenic, uncloned SIVsmE660 viral stock following vaccination with live attenuated SIVmac251/C8. MCM provided a characterised host genetic background with limited Major Histocompatibility Complex (MHC) and TRIM5α allelic diversity. Early protection, observed as soon as 3 weeks post-vaccination, was comparable to that of 20 weeks vaccination. Recrudescence of vaccine virus was most pronounced in breakthrough cases where simultaneous identification of vaccine and challenge viruses by virus-specific PCR was indicative of active co-infection. Persistence of the vaccine virus in a range of lymphoid tissues was typified by a consistent level of SIV RNA positive cells in protected vaccinates. However, no association between MHC class I/II haplotype or TRIM5α polymorphism and study outcome was identified.
  
  
  CONCLUSIONS
  This SIV vaccine study, conducted in MHC-characterised MCM, demonstrated potent protection against the pathogenic, heterologous SIVsmE660 challenge stock after only 3 weeks vaccination. This level of protection against this viral stock by intravenous challenge has not been hitherto observed. The mechanism(s) of protection by vaccination with live attenuated SIV must account for the heterologous and early protection data described in this study, including those which relate to the innate immune system.
authors.affiliation: Division of Retrovirology, National Institute for Biological Standards and Control, Health Protection Agency, South Mimms, Potters Bar, Hertfordshire, United Kingdom. neil.berry@nibsc.hpa.org.uk
authors.forename: Neil
authors.initials: N
authors.lastname: Berry
authors.forename: Claire
authors.initials: C
authors.lastname: Ham
authors.forename: Edward T
authors.initials: ET
authors.lastname: Mee
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Rose
authors.forename: Giada
authors.initials: G
authors.lastname: Mattiuzzo
authors.forename: Adrian
authors.initials: A
authors.lastname: Jenkins
authors.forename: Mark
authors.initials: M
authors.lastname: Page
authors.forename: William
authors.initials: W
authors.lastname: Elsley
authors.forename: Mark
authors.initials: M
authors.lastname: Robinson
authors.forename: Deborah
authors.initials: D
authors.lastname: Smith
authors.forename: Deborah
authors.initials: D
authors.lastname: Ferguson
authors.forename: Greg
authors.initials: G
authors.lastname: Towers
authors.forename: Neil
authors.initials: N
authors.lastname: Almond
authors.forename: Richard
authors.initials: R
authors.lastname: Stebbings
mesh_terms: D000483:Alleles; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics; D004279:DNA, Viral / Q000276:immunology; D006239:Haplotypes / Q000235:genetics; D017403:In Situ Hybridization; D007700:Kinetics; D018655:Lymphocyte Count; D008221:Lymphoid Tissue / Q000473:pathology / Q000821:virology; D008252:Macaca fascicularis / Q000276:immunology* / Q000821:virology*; D008285:Major Histocompatibility Complex / Q000235:genetics; D008436:Mauritius; D011110:Polymorphism, Genetic; D012367:RNA, Viral / Q000097:blood / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D012008:Recurrence; D018449:SAIDS Vaccines / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity; D013045:Species Specificity; D016896:Treatment Outcome; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D002352:Carrier Proteins; D004279:DNA, Viral; D012367:RNA, Viral; D018449:SAIDS Vaccines; D014613:Vaccines, Attenuated