Augmentation by Interleukins of the Antibody Response to a Conjugate Vaccine against Haemophilus influenzae B
Interleukins have been recognized as potential adjuvants for use during vaccination. The immunogenicity of some poorly immunogenic bacterial capsular polysaccharides have been improved by conjugation to a protein carrier. Augmentation of the immune response to these glycoconjugates, however, may be realized in the presence of interleukins. The antibody response to one such vaccine which comprises a oligosaccharide derived from the capsule of Haemophilus influenzae type b coupled to CRM197 (HbOC) can be augmented in this manner. A suboptimal dose (0.1 μg) of HbOC and varying concentrations of IL−1α or IL−1β (102 − 5 × 105 U) were injected intramuscularly at 0 and 2 weeks into Swiss Webster mice. Vaccines were also formulated with and without aluminum phosphate. Antibody to the oligosaccharide was determined by Farr assay. In 3/3 experiments, IL−1α enhanced primary and secondary antibody responses whereas with IL−lβ, only a slight increase in the primary antibody response was seen but enhanced secondary responses were observed. Thus, IL-la and to some extent,IL−1β enhanced the primary and secondary antibody responses to a glycoconjugate vaccine.
KeywordsAntibody Response Haemophilus Influenzae Conjugate Vaccine Immature Host Primary Immunization
Unable to display preview. Download preview PDF.
- Anderson, P. W. and Eby, R.J., 1987, European Patent 0-245-045-A2, Praxis Biologics, Inc.Google Scholar
- Anderson, P. W. and Eby, R. J., 1990, U. S. Patent 4,902,506, University of Rochester.Google Scholar
- Booth, R. J., Prestige, R. L., and Waston, J. D., 1983, Constitutive production by the WEHI-3 cell line of a B cell growth and differentiation factor that co-purifies with interleukin 1, J. Immunol., 131:577.Google Scholar
- Eby, R. J., Madore, D., Johnson, C., Smith, D.H., Connelly, B., McHenry, C. L., and Meyers, M., 1986, A new stable vaccine for Haemophilus influenzae b highly immunogenic for human infants composed of oligosaccharides of capsular polymer (PRP) linked to CRM197, Pediatr. Res., 20:308A.Google Scholar
- Hoffman, M. K., 1979, Control of B cell differentiation by macrophages, Ann. N. Y. Acad. Sci., 322:577.Google Scholar
- Hoffman, M.K., Gilbert, K.M., Hirst, J. A., and Scheid, M., 1987, An essential role for interleukin 1 and a dual function for interleukin 2 in the immune response of murine B lymphocytes to sheep erythrocytes, J. Mol. Cell. Immunol., 3:29.Google Scholar
- March, C. J., Mosley, B., Larsen, A., Cerretti, P., Braedt, G., Price, V., Gillis, S., Henny, C.S., Kronheim, S.R., Grabstein, K., Conlon, P. J., Hopp, T. P., and Cosman, D., 1985, Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs, Nature, 315:641.PubMedCrossRefGoogle Scholar
- Schnader, J. W., 1973, Mechanism of activation of the bone-marrow-derived lymphocyte. III. A distinction between a macrophage-produced triggering signal and the amplifying effect on trigger B lymphocytes of allogeneic interactions, J. Exp. Med., 138:1446.Google Scholar