Toxicology, biodistribution and shedding profile of a recombinant measles vaccine vector expressing HIV-1 antigens, in cynomolgus macaques.

As a new human immunodeficiency virus type 1 (HIV-1) vaccine approach, the live-attenuated measles virus (MV) Schwarz vaccine strain was genetically engineered to express the F4 antigen (MV1-F4). F4 is a fusion protein comprising HIV-1 antigens p17 and p24, reverse transcriptase and Nef. This study assessed the toxicity, biodistribution and shedding profiles of MV1-F4. Cynomolgus macaques were intramuscularly immunized one or three times with the highest dose of MV1-F4 intended for clinical use, the reference (Schwarz) measles vaccine or saline, and monitored clinically for 11 or 85 days. Toxicological parameters included local and systemic clinical signs, organ weights, haematology, clinical and gross pathology and histopathology. Both vaccines were well tolerated, with no morbidity, clinical signs or gross pathological findings observed. Mean spleen weights were increased after three doses of either vaccine, which corresponded with increased numbers and/or sizes of germinal centers. This was likely a result of the immune response to the vaccines. Either vaccine virus replicated preferentially in secondary lymphoid organs and to a lesser extent in epithelium-rich tissues (e.g., intestine, urinary bladder and trachea) and the liver. At the expected peak of viremia, viral RNA was detected in some biological fluid samples from few animals immunized with either vaccine, but none of these samples contained infectious virus. In conclusion, no shedding of infectious viral particles was identified in cynomolgus monkeys after injection of MV1-F4 or Schwarz measles vaccines. Furthermore, no toxic effect in relation to the MV vaccination was found with these vaccines in this study.

Local reactions of the saponin Quil A and a Quil A containing iscom measles vaccine after intramuscular injection of rats: a comparison with the effect of DPT-polio vaccine.

A short-term toxicity study was performed to investigate local reactions and hematological changes after im injection of Quillaia A (Quil A; 50 or 600 micrograms/ml) an essential component of an immunostimulating complex (iscom), a novel form of a subunit vaccine, and of iscom measles vaccine containing 360 micrograms Quil A/ml. The effects were compared with those caused by a sterile phosphate-buffered saline solution and by diphtheria-pertussis-tetanus-polio (DPT-polio) vaccine. Groups of six male rats were injected im with 0.25 ml of the test solution: on Day 0 in the left and on Day 7 in the right musculus gastrocnemius. On Day 14 the animals were killed, and the left and right inguinal lymph nodes were weighed. These organs and the left and right musculus gastrocnemius were investigated microscopically. The only hematological changes observed occurred in the group injected with DPT-polio vaccine: a decrease in the Hb value and in the number of erythrocytes and an increase in mean corpuscular hemoglobin content and in the number of leucocytes. The weights of the left and right inguinal lymph nodes were significantly increased in rats injected with DPT-polio vaccine, iscom measles vaccine, and the high dose of Quil A. The most intense granulomatous inflammatory reaction, mainly consisting of activated macrophages, was observed at the injection sites of all animals of the DPT-polio group. Only one animal injected with the iscom measles vaccine showed a moderate inflammatory reaction of the same type.(ABSTRACT TRUNCATED AT 250 WORDS)