title: Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.
abstract: Groups of rhesus monkeys were vaccinated and boosted with Mycobacterium bovis bacillus Calmette Guerin (BCG) or BCG plus low-dose (LD) or high-dose (HD) heat-killed M. leprae (HKML), or were unvaccinated. Prior to and following vaccination-boosting and subsequent M. leprae (ML) challenge, these and unvaccinated, unchallenged control monkeys were observed longitudinally for approximately 3 years. Vaccination with BCG plus HKML initially stimulated significant in vitro blood mononuclear cell blastogenic responses to lepromin, which returned to baseline post-boosting and post-live-ML-challenge, minimally reappearing significantly 2 years post-ML-challenge. Vaccination with BCG failed to stimulated positive blastogenic responses to lepromin before ML-challenge but small, marginally positive, intermittent responses were seen post-ML-challenge. Compared to the unvaccinated ML-challenged group, significant increases in the numbers of blood CD4+ and CD8+ T-cell subsets and an increased CD4+:CD8+ ratio were observed in both BCG plus HKML-vaccinated, ML-challenged groups, but not in the BCG-only-vaccinated, ML-challenged group. CD4+CD29+ and CD4+CD45RA+ subset numbers increased significantly over time in only the BCG plus LD HKML-vaccinated, ML-challenged group. Compared to unvaccinated, ML-challenged groups, vaccination with BCG or BCG plus HKML followed by ML-challenge produced lower IgM:IgG antiphenolic glycolipid-I (PGL-I) serum antibody ratios and protected rhesus monkeys from clinical leprosy, consistent with prior observations that low IgM:IgG anti-PGL-I responses correlated with resistance to and protection from leprosy.
authors.affiliation: Department of Microbiology, Tulane Regional Primate Research Center, Covington, LA 70433, USA. gormus@tpc.tulane.edu
authors.forename: B J
authors.initials: BJ
authors.lastname: Gormus
authors.forename: G B
authors.initials: GB
authors.lastname: Baskin
authors.forename: K
authors.initials: K
authors.lastname: Xu
authors.forename: M S
authors.initials: MS
authors.lastname: Ratterree
authors.forename: L N
authors.initials: LN
authors.lastname: Martin
authors.forename: P A
authors.initials: PA
authors.lastname: Mack
authors.forename: R P
authors.initials: RP
authors.lastname: Bohm
authors.forename: W M
authors.initials: WM
authors.lastname: Meyers
authors.forename: G P
authors.initials: GP
authors.lastname: Walsh
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology; D016516:CD4-CD8 Ratio; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006017:Glycolipids / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007918:Leprosy / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D008137:Longitudinal Studies; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D009166:Mycobacterium leprae / Q000276:immunology*; D012588:Scintillation Counting; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D017778:Vaccines, Combined / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001428:Bacterial Vaccines; D006017:Glycolipids; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014613:Vaccines, Attenuated; D017778:Vaccines, Combined; C045169:phenolic glycolipid I, Mycobacterium leprae