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.