Booster vaccination against diphtheria and tetanus in man. Comparison of three different vaccine formulations--III.

Adverse reactions and antibody levels were compared following a booster vaccination of 177 Danish military recruits with a plain, an aluminium hydroxide (0.5 mg Al per human dose, HD) and a calcium phosphate (0.25 mg Ca per HD) adsorbed diphtheria-tetanus (D-T) vaccine. The calcium phosphate adsorbed vaccine was given in a HD of 3 Lf of D and T toxoids and proved to be of equal efficacy as the aluminium hydroxide adsorbed vaccine which was injected in a dose containing twice the antigen amount. The calcium phosphate vaccine caused fewer adverse reactions than the one adsorbed to aluminium hydroxide. The plain vaccine (6 Lf per HD of D and T toxoid) had the highest efficacy with a similar low occurrence of adverse reactions as the calcium phosphate adsorbed vaccine. Potency assays in mice were in accordance with these immunogenicity results in man if a two dose immunization schedule was followed, but not if the vaccines were compared after a single immunization as requested by the procedure for potency testing according to current WHO and European Pharmacopoeia requirements. Both of the adsorbed vaccines primed mice for specific IgE antibody formation. This could be detected after a second immunization with either of the adsorbed vaccines or with the plain D-T vaccine. Also in humans, immunization with the plain vaccine boosted specific IgE formation to a detectable level. This may be ascribed to adjuvant priming during the primary vaccination series some 20 years previously.

Adjuvanticity of aluminium hydroxide and calcium phosphate in diphtheria-tetanus vaccines--I.

The potencies of two diphtheria-tetanus vaccines (DT) adsorbed to either aluminium hydroxide or calcium phosphate were compared in mice and guinea pigs. The vaccines were made from the same batches of purified toxoids and contained the same amounts of antigens. Immunizations were done once or twice with different doses of vaccine injected undiluted, diluted in saline or diluted in the corresponding adjuvant. The various potency assays showed that the adjuvanticity of calcium phosphate was lower than or equal to aluminium hydroxide. Despite the range of potency assays done, none of the methods reflected the efficacy of these vaccines in revaccination of humans. A simplified potency assay is suggested for release of final vaccine formulations to reduce the number of animals in quality control.

Booster vaccination against diphtheria and tetanus in man. Comparison of calcium phosphate and aluminium hydroxide as adjuvants--II.

Diphtheria and tetanus antibody levels were measured before and four weeks after booster vaccination of 313 Danish military recruits participating in a clinical trial to compare aluminium hydroxide and calcium phosphate as adjuvants in diphtheria-tetanus vaccines (DT). Twenty-eight percent of the men had a diphtheria pre-vaccination content below a protective level of 0.01 IU ml-1. The calcium phosphate adsorbed vaccine showed the highest efficacy for both antigens. Adverse reactions were rare but more frequent in the calcium group than in the aluminium group. No correlation was found between pre- or post-vaccination levels and adverse reactions and both vaccines gave rise to specific IgE formation. The results show that calcium phosphate is more effective but not a safer alternative to aluminium hydroxide when compared in vaccines containing 1.0 mg ml-1 of Ca or of Al.