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Killed Listeria monocytogenes vaccine is protective in C3H/HeJ mice without addition of adjuvants

Naturevolume 286pages713714 (1980) | Download Citation



Resistance of mice to the facultative intracellular parasite Listeria monocytogenes involves cellular immunity1, as it can be transferred passively with viable lymphoid cells2 but not with serum. Induction of protective immunity can only be achieved by vaccination with sublethal numbers of viable listeria3,4 or with dead Usteria in combination with certain adjuvants5,6. Killed listeria vaccines as such are not protective. Effective adjuvants are lipopolysaccharide (LPS)5, dextran sulphate (molecular weight 500,000) and suramin6, whereas Freund's complete adjuvant is ineffective6. All these polyanionic substances have a shortlived deleterious effect on macrophage function5–7. It seems necessary for their adjuvant activity that they be present during the induction of immunity, most prqbably resulting in incomplete degradation of the dead listeria within the macrophage. During the effector phase, however, the adjuvants need to be virtually absent8,9, so that macrophages are unhampered in eliminating the infective bacteria of an eliciting listeria injection. We describe here our finding that LPS-nonresponder C3H/HeJ mice, unlike H–2 identical C3HeB/FeJ or H–2 unrelated mice, can develop resistance to a lethal dose of viable L. monocytogenes on a single injection with dead listeria vaccine without any adjuvant added. This suggests that the C3H/HeJ mouse has some kind of ‘intrinsic adjuvant’. If present, such an intrinsic adjuvant would, in analogy to the effective adjuvants5–7, probably be a polyanionic substance. By means of protamin precipitation10, we have found evidence for the presence of such a substance in the serum of C3H/HeJ mice.

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  1. 1

    Mackaness, M. B. J. exp. Med. 116, 381–406 (1962).

  2. 2

    Mackaness, M. B. J. exp. Med. 129, 973–992 (1969).

  3. 3

    Hasenclever, H. F. & Karakawa, W. W. J. Bact. 74, 584–586 (1957).

  4. 4

    Kerckhaert, J. A. M., Hofhuis, F. M. A. & Willers, J. M. N. Immunology 32, 1027–1032 (1977).

  5. 5

    Rodriguez, G. E., McClatchy, J. K. & Campbell, P. A. Infect. Immun. 10, 1163–1169 (1974).

  6. 6

    Van der Meer, C., Hofhuis, F. M. A. & Willers, J. M. N. Nature 269, 594–595 (1977).

  7. 7

    Willers, J. M. N. et al. Antonie van Leeuwenhoek 45, 41–48 (1979).

  8. 8

    Hahn, H. Infect. Immun. 10, 1105–1109 (1974).

  9. 9

    Hahn, H. & Bierther, M. Infect. Immun. 10, 1110–1119 (1974).

  10. 10

    Graham, D. T., Pomeroy, A. R. & Smythe, D. B. Thromb. Haemostasis (Stuttg.) 41, 583–589 (1979).

  11. 11

    Ruco, L. P. & Meltzer, M. S. J. Immun. 120, 329–334 (1978).

  12. 12

    Vogel, S. N. & Rosenstreich, D. L. J. Immun. 123, 2842–2850 (1979).

  13. 13

    Mayer, M. M. in Experimental Immunochemistry 2nd edn (eds Kabat, E. A. & Mayer, M. M.) 133 (Thomas, Springfield, 1961).

  14. 14

    Hoffmann, M. K. J. Immun. 121, 619–621 (1978).

  15. 15

    Van Dijk, H., Van Heuven-Nolsen, D., Rademaker, P. M., Bloksma, N. & Willers, J. M. Cell Immun. 51, 402–407 (1980).

  16. 16

    Jaques, L. B. Science 206, 528–533 (1979).

  17. 17

    Mahadoo, J. & Jaques, L. B. Med. Hypoth. 5, 835–842 (1979).

  18. 18

    Weiler, J. M., Yurt, R. W. & Austen, K. F. J. Immun. 120, 1802 (1978).

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  1. Immunology Section of the Laboratory of Microbiology, State University, Catharijnesingel 59, 3511 GG, Utrecht, The Netherlands

    • Hans van Dijk
    • , Frans M. A. Hofhuis
    • , Els M. J. J. Berns
    • , Cees van der Meer
    •  & Jan M. Willers


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