Combined vaccination with BCG and toxoid antigens.

Simultaneous vaccination with different antigens has been widely practised in recent years. A notable example is percutaneous smallpox vaccination together with the intradermal injection of BCG. In contrast, the potentially even more time-saving procedure of combined vaccination (i.e., with vaccines mixed prior to injection) has been tried on only a very limited, experimental scale. Combined vaccination with a mixture of BCG and toxoids has not been suggested before. Such a mixed vaccine, with diphtheria and tetanus toxoids, was used in experiments in vitro and in vivo.No deleterious effect of toxoids on BCG was found in terms of reduction in oxygen uptake, germination rate, or counts of viable particles. The dose-response relationships (delayed hypersensitivity and skin reactivity) for BCG with and without added toxoids were compared in guinea pigs and no differences were found. The antibody response in guinea pigs to toxoids mixed with BCG or with aluminium hydroxide was measured following both primary and booster immunization. The primary response to toxoids was lower with BCG than with aluminium hydroxide. In booster immunization, the response was identical for the two mixtures.It appears that not only is a mixture of toxoids and BCG innocuous (given intradermally) but also BCG may have an adjuvant effect on the production of antibodies to the toxoids. Further experimentation is needed, first in the guinea pig model and later in pilot trials in man, to establish suitable dose levels. Furthermore, since BCG may act as an adjuvant both in producing antibodies and in the cell-mediated response to the toxoids, it would be desirable to clarify the possible interaction of these two immune responses in protection against disease.

In vitro stimulation of human lymphocytes by Bordetella Pertussis.

Bordetella pertussis (B.p.) induces blast transformation of human lymphocytes; whole killed B.p. are more efficient than extracts obtained by sonication. Similar responses were obtained with each of the four strains used in the Danish pertussis vaccine. B.p. with low amounts of Protective Antigen and Histamine-Sensitizing Factor also induced lymphocyte transformation, but were less toxic to the lymphocytes at high concentrations. The supernatants of B.p. cultures were purified with respect to Lymphocytosis Promoting Factor; evidence is presented that these purified fractions possess T-lymphocyte mitogenic activity. Lymphocytes from all normal humans were stimulated by B.p., including cells from cord blood. Cells from childbearing women, obtained immediately after delivery, showed a general depression of lymphocyte transformation including the response to B.p. Children with whooping cough had a lower lymphocyte response to B.p. than healthy children. A highly significant correlation was observed between the responses to B.p. and to E. coli in the adults and newborn examined. It is concluded that the major part of the lymphocyte transformation induced by B.p. is non-specific.