Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations.
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.
Gormus
B J
BJ
Department of Microbiology, Tulane Regional Primate Research Center, Covington, LA 70433, USA. gormus@tpc.tulane.edu
Baskin
G B
GB
Xu
K
K
Ratterree
M S
MS
Martin
L N
LN
Mack
P A
PA
Bohm
R P
RP
Meyers
W M
WM
Walsh
G P
GP
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
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