Monophosphoryl lipid A behaves as a T-cell-independent type 1 carrier for hapten-specific antibody responses in mice.
It is known that the lipopolysaccharide (LPS) of gram-negative bacteria, in addition to being a potent adjuvant, is an effective carrier for covalently associated haptens. However, the toxic nature of most forms of LPS precludes their use as adjuvants or carriers for human vaccines. 4'-Monophosphoryl lipid A (MLA), a derivative of LPS with attenuated toxicity, is currently being tested in humans as an immunological adjuvant. In this study, MLA was tested for its ability to function as a carrier for a small hapten, the trinitrophenyl group (TNP). MLA was first modified by addition of 6-aminocaproic acid to the 6' position of the disaccharide backbone (Cap-MLA). TNP was then attached to Cap-MLA via the free amino group, yielding TNP-Cap-MLA. Immunization of normal mice with TNP-Cap-MLA resulted in high-titer anti-TNP responses of immunoglobulin M and all immunoglobulin G subclasses. Furthermore MLA, like other T-cell-independent type 1 (TI-1) carriers, induced responses in athymic and X-linked immunodeficient mice. In all cases, immunization with either MLA alone or TNP-Cap plus MLA failed to induce measurable anti-TNP antibodies of any isotype, indicating that covalent association of MLA and hapten was necessary for MLA's carrier activity to be manifested. These properties of MLA make it a potential candidate as a carrier for vaccine subunit components, such as small peptides, especially for situations in which T-cell help is impaired, as occurs following human immunodeficiency virus type 1 infection.
Myers
K R
KR
Ribi ImmunoChem Research, Inc., Hamilton, Montana 59840.
Beining
P
P
Betts
M
M
Snippe
H
H
Inman
J
J
Golding
B
B
D000818:Animals; D000917:Antibody Formation; D000955:Antigens, T-Independent / Q000276:immunology*; D005260:Female; D006241:Haptens / Q000276:immunology*; D007154:Immune System Diseases; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D008819:Mice, Nude; D012729:Sex Chromosome Aberrations; D013045:Species Specificity; D014301:Trinitrobenzenes / Q000276:immunology*
D000955:Antigens, T-Independent; D006241:Haptens; D008050:Lipid A; C091197:N-(2,4,6-trinitrophenyl-6-aminocaproyl)-4'-monophosphoryl lipid A; D014301:Trinitrobenzenes