Monophosphoryl lipid A behaves as a T-cell-independent type 1 carrier for hapten-specific antibody responses in mice
| Autor: | P R Beining, K R Myers, M Betts, H Snippe, Basil Golding, John K. Inman |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
medicine.medical_treatment
education Immunology Mice Nude Monophosphoryl Lipid A chemical and pharmacologic phenomena Microbiology Immunoglobulin G Lipid A Mice Species Specificity Antigen medicine Animals Sex Chromosome Aberrations Mice Inbred BALB C biology Antigens T-Independent Isotype Molecular biology Mice Mutant Strains Infectious Diseases Immune System Diseases Mice Inbred DBA Trinitrobenzenes Antibody Formation Mice Inbred CBA biology.protein Female Parasitology Antibody Haptens Hapten Adjuvant Research Article |
| Zdroj: | Infection and Immunity. 63:168-174 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.63.1.168-174.1995 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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