Preclinical safety testing of the Quimi-Hib(r) vaccine adjuvanted with aluminum phosphate during product development

Haemophilus influenzae type b (Hib) is a Gram-negative bacterium causing diseases such as meningitis, pneumonia, epiglottis, cellulitis, septicemia and arthritis, among others. Hib-caused meningitis / Hib meningitis is a very seri- ous disease with a death rate of more than 50 % throughout the world; therefore obtaining a vaccine against this bacterium is a goal of the highest priority. The present report presents the results of preclinical safety testing of the Quimi-Hib® vaccine (synthetic Hib antigen conjugated to tetanus toxoid) adjuvanted with aluminum phosphate. The battery of toxicological tests included acute toxicity (15 days), local tolerance (15 days) and repeated-dose toxicity (30 days), all of them evaluating the therapeutic dose of the vaccine as part of the studied experimental treatments. Three vaccine dose levels and a placebo (excipients plus adjuvant) were examined, administering the vaccine in- tramuscularly to Sprague Dawley rats of both sexes. After examining the data obtained from the administration of this wide range of doses to Sprague Dawley rats, it was concluded that the synthetic conjugate vaccine Quimi-Hib® adjuvanted in aluminum phosphate is not toxic and does not cause systemic adverse effects. No macroscopic altera- tions were observed in the studied organs, and the evaluation of the inoculation site only detected indurations caused by macrophage granulomas, resulting from the mechanism of action of the adjuvant included in the formulation.