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

Abstract

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 listeria^3,4 or with dead Usteria in combination with certain adjuvants^5,6. 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 function^5–7. 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 absent^8,9, 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 adjuvants^5–7, 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.