title: Antileprosy protective vaccination of sooty mangabey monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.
abstract: Groups of sooty mangabey monkeys (SMM) were vaccinated and boosted with Mycobacterium bovis bacillus Calmette-Guerin (BCG), or BCG + 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 immunologically observed longitudinally for approximately 3 years. SMM [multibacillary (MB) leprosy-prone as a species] were not protected clinically by BCG or BCG + HKML, although the disease progress was slowed by vaccination with BCG alone. The longitudinal immune response profiles to BCG or BCG + HKML in SMM showed that: 1) vaccination with BCG or BCG + HKML initially stimulated significant in vitro blood mononuclear cell blastogenic responses to ML antigens, which returned to baseline post-boosting and post-live ML challenge; 2) BCG + LD HKML-vaccinated groups gave the largest blastongenic response (SI = 23) followed by the BCG + HD HKML group (SI = 14.5) and by the BCG-only vaccinated group (SI = 3.6); 3) significantly diminished numbers of blood CD4+ (helper) and CD4+CD29+ (helper-inducer) T-cell subsets were observed longitudinally in all ML-challenged groups compared to controls regardless of whether they had been vaccinated or not; 4) CD8+ (suppressor) T-cell numbers remained longitudinally constant, on average, in all ML-challenged groups (vaccinated or not) compared to controls; 5) there was a significant decrease in the CD4+:CD8+ ratio over time in all ML-challenged groups (vaccinated or not); 6) vaccination with BCG or BCG + LD or HD HKML resulted in significantly increased numbers of CD4+CD45RA+ (suppressor-inducer) T cells longitudinally compared to the unvaccinated, ML-challenged control group; and 7) over time, vaccination with BCG + HKML followed by live ML-challenge produced higher IGM:IgG antiphenolic glycolipid-I (PGL-I) serum antibody response ratios than BCG-only vaccinated, ML-challenged monkeys or unvaccinated, ML-challenged SMM, consistent with prior observations that IgG anti-PGL-I responses correlate with resistance to and protection from clinical leprosy and IgM anti-PGL-I responses correlate with increased susceptibility.
authors.affiliation: Department of Microbiology, Tulane Regional Primate Research Center, 18703 Three Rivers Road, Covington, Louisiana 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: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000032:analysis; D016665:Cercocebus atys; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006017:Glycolipids / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D019012:Integrin beta1 / Q000032:analysis; D007918:Leprosy / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D017493:Leukocyte Common Antigens / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D009166:Mycobacterium leprae / Q000276:immunology; D014611:Vaccination; D017778:Vaccines, Combined; D015164:Vaccines, Inactivated / Q000008:administration & dosage
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001428:Bacterial Vaccines; D015704:CD4 Antigens; D016827:CD8 Antigens; D006017:Glycolipids; D019012:Integrin beta1; D017778:Vaccines, Combined; D015164:Vaccines, Inactivated; C045169:phenolic glycolipid I, Mycobacterium leprae; D017493:Leukocyte Common Antigens