Leo Levine

Tetanus-toxoid emergency boosters. A reappraisal.

Abstract Measurement of tetanus antibody titers in 143 pediatric patients receiving routine and emergency immunization according to current practice showed that none who had received four or more injections failed to maintain the accepted protective level of 0.01 AU per milliliter for any measured interval. Analysis of the data indicated that the interval of protection after four or more injections is greater than 12 years from the last injection, with a confidence level of 99.9 per cent. When there is a valid history of the routine schedule of immunization outlined, special tetanus boosters on admission to camps, schools and colleges and emergency injections at times of injury should be abandoned, to minimize toxoid reactions. The risk of contracting tetanus if these recommendations are followed is calculated to be so remote as to approximate zero.

A field study in triple immunization (diphtheria, pertussis, tetanus). Estimation of 3 antibodies in infant sera from a single heel puncture using agglutination techniques.

Summary A useful field study in multiple immunization was described, which was carried out within the routine of a private pediatric practice with a minimum of inconvenience to the child. This was made possible by the high sensitivity of the agglutination techniques whereby reliable antibody titers to three antigens, diphtheria and tetanus toxoids and pertussis vaccine, were obtained for each treatment group from single heel punctures. The methods were described and the evidence of their validity discussed. The validity of the hemagglutination method is supported by the facts that the results show clear dependence on the number of antigen doses injected and a reasonable decline in time after the last antigen injection.

Properties of the immunogenic and sensitizing activities of Bordetella pertussis in mice: I. Enhancement of peptone shock

Abstract The capacity of pertussis vaccine to enhance peptone shock in mice paralleled the immunogenic and histamine-sensitizing activities in fractionation and was similarly labile to heat and to tryptic degradation. It is, therefore, suggested that the immunogen itself may be responsible for these sensitizing activities. Elicitation of heightened susceptibility to peptone shock by the administration of a beta-adrenergic blocking agent, propranolol, would suggest that pertussis vaccine may induce this effect, as had earlier been reported and is presently confirmed, with histamine, via autonomic nervous pathways. Several significant differences were found, however, between pertussis-mediated hypersensitivity to histamine and to peptone, including degree of sensitivity engendered, mouse strain specificity, and duration of symptoms.

Properties of the immunogenic and sensitizing activities of Bordetella pertussis in mice

Abstract The component of Bordetella pertussis that enhances the susceptibility of mice to challenge with homologous and heterologous endotoxin parallels the protective antigen and histamine-sensitizing factor (HSF) during chemical fractionation of pertussis vaccine. This finding, together with evidence of the lability of all three of the above activities to heat and trypsin, adds another to the lengthening list of sensitizing activities of pertussis vaccine in mice that share these same properties. This is consistent with our thesis that all of the diverse sensitizing activities of pertussis vaccine are functions of the immunogen itself. The induction by endotoxin of a state of partial tolerance to a subsequent injection of a lethal dose of endotoxin was confirmed. This, in addition to the findings of others, would appear to eliminate the lipopolysaccharide component of pertussis vaccine as the agent that elicits hyper-reactivity to bacterial endotoxins. It is postulated that the combined effects on the autonomic nervous system of the sensitizing component in pertussis vaccine and the challenge endotoxin itself are responsible for this hypersensitivity state in mice.

Host Factors in the Response to Immunization

Aside from the scientific concepts that arouse interest for their own sake in the factors that determine the character and magnitude of the response to immunization, the subject has many self-evident practical applications. Until recently, problems raised by the limitations in the response to immunization have generally been side-stepped by simple empirical solutions such as injecting more antigen per dose, or giving more injections. However, this approach is frustrating, not only because it is empirical (and not always rational), but also because it requires money, personnel and logistic facilities that can be provided, as a rule, only in the affluent countries. For the developing countries there is a real need for more simplified immunization schedules; and it is largely with this objective in mind that our more recent studies on the factors affecting the immune response have been carried out.