Experimental study upon the efficacy of some accelerated vaccination schedules in tetanus prophylaxis.

In an attempt to accelerate the antitetanic vaccine-induced immune response necessary particularly in subjects with tetanigenic wounds, groups of guinea pigs or rabbits were i.d. or s.c. immunized with a nonadsorbed purified and concentrated toxoid. Concomitantly, lots of control animals were i.m. immunized with tetanic vaccine adsorbed on aluminium phosphate. The immune response was estimated by testing the serum antitetanus antitoxic titre and the resistance of guinea pigs to tetanic intoxication. The results obtained revealed a variety of responses to vaccination in which differed terms of the species of animals and the applied immunization schedule. When single vaccine doses were used the protective antitetanus limit was reached in seven days in rabbits and after ten days in guinea pigs; the adsorbed vaccine induced a stronger immune response than the non-adsorbed vaccine. When multiple immunization doses were used the non-adsorbed tetanus vaccine induced, especially in rabbits, a more rapid response that the adsorbed vaccine. The vaccination schedules used in laboratory animals and which have yielded the best results in this experiment will be analysed and checked on human subjects in a further study.

Investigations concerning the possibility to replace the Schick test by the passive hemagglutination reaction for evaluating the diphtheria immunity level in population.

The evaluation of Schick test results as compared to the results obtained by determination of diphtheria antitoxin concentration in blood using the neutralizing test on rabbit--Jensen on the one hand and to those obtained by the passive hemagglutination reaction on the other has revealed some discrepancies against the two tests: 7.09% (4.08% pseudo-protected, 3.01 pseudo-susceptible) as against TN-Jensen and 8.6% (5.59% pseudo-protected and 3.01% pseudo-susceptible) as against the passive hemagglutination reaction results. The reported discrepancies were due to the fact that the results of Schick test did not correlate perfectly with the amount of circulating antitoxin, the diphtheria immunity level was wrongly indicated by the Schick test. The passive hemagglutination reaction has proved to be adequate to mass-screening investigations being capable to replace Schick test.

Experimental study on intradermal antitetanus antityphoid immunization.

A new type of concentrated unadsorbed Tetanus vaccine was administered in animals by intradermal route, associated or not with Typhoid vaccine. The results of the laboratory tests demonstrated that this vaccine is innocuous and produces minimal reactions. A single doses of Tetanus vaccine inoculated in guinea pig or rabbit resulted in a relevant titer which increased when the Typhoid vaccine was associated. Also, in such immunized guinea pigs, a remarkable resistance to tetanic toxin was achieved. The levels of the active or passive typhoid-protective power as well as that of the agglutinating antibodies were not influenced by the association of the Tetanus vaccine to the Typhoid vaccine. Therefore, when the Typhoid vaccine suspended in Tetanus vaccine was administered intradermally to the animals by Jet injector, it had not a negative effect for none of the two components, had a beneficial effect upon the levels of determined antibody production and allowed an easier and more rapid administration of these vaccines.

Intradermal antitetanic-antityphoid booster by jet injection.

The immunogenicity and the reactogenicity of an unadsorbed Tetanus vaccine, intradermally administered in man as a booster immunization associated or not with lyophilized Typhoid vaccine, were comparatively studied. There were no differences in postvaccinal reactions between the Tetanus vaccine administered alone or associated with Typhoid vaccine as well as between the unadsorbed and adsorbed Tetanus vaccine. The booster inoculation carried out with Tetanus vaccine by i.d. route with doses of 10 Lf/0.1 ml proved to be effective, inducing to all the subjects a definite protective titre, maintaining for at least one year.

Intradermal antityphoid-antitetanus vaccination by jet injection.

A lyophilized, heat-killed, phenol preserved typhoid vaccine (5 x 10(8) cells) suspended in 0.1 ml unadsorbed concentrated tetanus vaccine (10 Lf) was administered in man by intradermal route. This association of the two vaccines resulted in milder postvaccinal reactions: moreover, the immunological properties of typhoid vaccine, as certified by the passive protection test of the mouse with sera of the vaccines and the H and O agglutinin titres found in these immune sera, were perfectly conserved. Consequently, the mixed typhoid-tetanus vaccination in man by intradermal route is possible and advantageous for practical and economical reasons.

Study of specific immune response to unadsorbed concentrated tetanus vaccine administered by intradermal route to non-immunized persons in the last ten years.

Investigations of anti-tetanus response, in 404 subjects, most of them aged 60, being non-immunized for at least 10 years, stressed out the fact that 28.7% were not protected and 6.18% presented a protecting titer of 0.01 IU/ml, evaluated by "in vivo" protection test in mice. Some subjects were immunized with unadsorbed Tetanus vaccine (10 Lf/0.1 ml/dose) by i.d. route, using Jet-injector, and the others with adsorbed Tetanus vaccine (0.5 ml/dose), by i.m. route, using the needle and syringe. The vaccines were well tolerated and adverse reactions were not recorded. After 30 days, a single vaccine dose produced a protecting effect in 97.45% of non-protected subjects, belonging to i.d. immunized group, and also in 93.33% belonging to i.m. immunized group. 30 days after the administration of a second dose, protection set up in all subjects, no matter of vaccine type and administration route used. For a continuous reduction of tetanus morbidity, the authors suggest a specific periodical immunization of non-protected persons, selected by serological screening, using unadsorbed Tetanus vaccine, administered by i.d. route by means of the Jet-injector.

[The relationships between antitoxic titers determined in a group of young people before and after booster ADT by the in vivo neutralization test. Comparative NT-PHAR evaluations]. / Relations entre les titres antitoxiques déterminés sur un lot de jeunes gens, avant et après le rappel à l'ATPA, par le test de neutralisation "in vivo". Evaluations comparatives TN-RHAP.

The geometrical mean of antitoxic titers determined in a lot of immunized young men who received, 5-7 years before, a booster with diphtheria-tetanus bivaccine, was of 1.54 (x/divided by 10.54) I.U./ml. At one month after another booster, performed with Tetanus toxoid (adsorbed), an increase of 34 times was recorded, the geometrical mean reaching the value of 52.67 (x/divided by 10.42 I.U./ml). The covering coefficients of the minimal protective antitoxin level have increased from 154 to 5267, in the estimation performed at the level of geometrical mean (calculating the ratio between the value of this indicator and that of the protection limit) and from 1623 to 54935, or from 15 to 505, respectively, in the estimations performed at the levels of the limits of the statistical range of one geometric standard deviation (Mg x/divided by D Sg). The study of the relations between pre- and post-antitoxic titers, performed by the linear regression analysis, leads to an equation whose slope evidenced the lower amplitude of the booster titers, along the increase of previous titers. The study of the inter-methods (neutralization-passive haemagglutination) regression allowed to obtain a correlation coefficient, between methods, of r = 0.83 and to perform the transposition of the minimal protective N.T. level (0.01 I.U.) in the terms of passive haemagglutination reaction, at the titer of 160 (0.3 PHAU/ml), for the p less than or equal to 0.05 probability level.

[The immunogenic capacity of soluble "vaccinia" antigen (fractionated smallpox vaccine) administered simultaneously with inactivated typhoid vaccine and with purified and concentrated tetanus anatoxin]. / La capacité immunogène de l'antigène soluble "vaccinia" (vaccin fractionné antivariolique) administré simultanément avec le vaccin typhoïdique inactivé et avec l'anatoxine tétanique purifiée et concentrée.

In this study we have investigated the immune humoral response in the associated vaccination with smallpox, tetanus and typhoid fractionated vaccine (trivaccine) administered in two series at 1 month interval, by dermojet, in a group of young people of 18-20 years old. The results were comparatively estimated with those obtained in two groups of young people of the same age (control group), separately immunized with two components of the tri-vaccine: fractionated smallpox vaccine and tetanus toxoid, following-up the humoral response to the two vaccine components. It was find that, at the end of the surveillance period, similar results were obtained for the testing group and control group, the antibody titers (in geometric mean) presenting very close values: 1/1,140,463 for the testing group, and 1/1,053,583 for the control group against vaccinia component, and 1/1,86,880,586 for the testing group and 1/79,900,431 for the control group, against the tetanus component. The results obtained entitle us to propose this vaccination scheme for the vaccination practice.