ABSTRACT
In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.
Neste estudo reportamos segurança e resposta de hipersensibilidade tardia (DTH) do antígeno sonicado de células totais de Leishmania donovani introduzidos juntamente com alume-BCG (AIBCG) Montanide ISA 720 (MISA) ou lípide A monofosforilado (MPLA) em grupos de macacos vervet. Depois de três injeções intradérmicas do inóculo nos dias 0, 28 e 42 segurança e resposta DTH foram avaliados. Preliminarmente níveis de fator de necrose tumoral alfa (TNF-α) e interferon gama (IFN-γ) foram também medidos e comparados com o DTH. Somente os animais imunizados com alume-BCG reagiram de maneira diversa ao inóculo produzindo indurações ulceradas e eritematosas na pele. Análise não paramétrica de variação seguida por um teste posterior mostraram resposta significantemente mais alta do DTH no grupo MISA + Ag quando comparado com outros grupos imunizados (p < 0.001). O grupo MPLA + Ag demonstrou resposta DTH significantemente menor do antígeno sonicado comparado com o grupo AIBCG + Ag. Houve correlação significante entre o DTH e a resposta às citocinas (p < 0.0001). Baseados neste estudo concluímos que o antígeno sonicado de Leishmania donovani contendo MISA 720 é seguro e está associado com forte reação DTH após imunização.
Subject(s)
Animals , Female , Male , Adjuvants, Immunologic/administration & dosage , Antigens, Protozoan/administration & dosage , Hypersensitivity, Delayed/immunology , Leishmania donovani/immunology , Leishmaniasis, Visceral/immunology , Lipid A/analogs & derivatives , Adjuvants, Immunologic/adverse effects , Chlorocebus aethiops , Enzyme-Linked Immunosorbent Assay , Interferon-gamma/blood , Lipid A/administration & dosage , Lipid A/adverse effects , Tumor Necrosis Factor-alpha/bloodABSTRACT
The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.