Immunogenicity of lipopolysaccharide derived from Brucella abortus: potential as a carrier in development of vaccines for AIDS.
In view of its unique ability to stimulate human B cells, we have considered using Brucella abortus (BA) as a carrier for human vaccines. Recently we showed that HIV-1 coupled to BA, but not unconjugated HIV-1, was able to stimulate murine responses even in the relative absence of CD4+ T cells. This result suggested that HIV-BA may be useful in boosting the immunity of individuals infected with HIV-1 and who have impaired CD4+ T cell function. In order to refine this carrier we purified lipopolysaccharide (LPS) from BA and examined its effects on immune responses. Similar to LPS from E. coli (LPS-EC), LPS-BA was capable of stimulating mouse B cells to proliferate. In addition, LPS-BA could activate mouse spleen cells to secrete antibodies in vitro. Isotype analysis revealed that IgM and all the IgG subclasses were elicited. When comparing these responses to those of LPS-EC, LPS-BA induced a greater percentage of IgG2a and LPS-EC evoked more IgG3. IgG2a is probably important in protection against murine viral infection. LPS-BA was haptenated with trinitrophenol TNP-LPS (BA) and tested for carrier effect. Similar to TNP-BA and TNP-LPS (EC), TNP-LPS (BA) triggered anti-TNP antibody of the IgM and all IgG subclasses. In contrast, TNP-ficoll induced mainly IgM and only small amounts of IgG3. These results suggest that LPS-BA, like intact BA, behaves as a T-independent type 1 carrier, and as such may be advantageous as a carrier for human vaccines development.
Goldstein
J
J
Division of Hematology, USFDA, Bethesda, MD 20892.
Hernandez
D
D
Frasch
C
C
Beining
P R
PR
Betts
M
M
Hoffman
T
T
Golding
B
B
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D002003:Brucella abortus / Q000276:immunology*; D004337:Drug Carriers; D006801:Humans; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C
D016915:AIDS Vaccines; D004337:Drug Carriers; D008070:Lipopolysaccharides