Oil-in-water emulsion adjuvant with influenza vaccine in young children.

BACKGROUND: The efficacy of inactivated influenza vaccines is known to be poor in infants and young children. METHODS: We studied the effect of the adjuvant MF59, an oil-in-water emulsion, on the efficacy of trivalent inactivated influenza vaccine (TIV) in 4707 healthy children 6 to less than 72 months of age who had not previously been vaccinated against influenza. The children were randomly assigned to three study groups, each of which received the assigned vaccines in two doses, 28 days apart, during two consecutive influenza seasons. Two of the groups were given age-appropriate doses of TIV either with or without the MF59 adjuvant, and the third group was given control (noninfluenza) vaccines to assess their absolute and relative efficacy against influenza-like illness, as confirmed by means of polymerase-chain-reaction (PCR) assay. RESULTS: Attack rates of influenza-like illness across both influenza seasons were 0.7%, 2.8%, and 4.7% in the adjuvant, nonadjuvant, and control vaccine groups, respectively. The absolute vaccine efficacy rates against all influenza strains (94 of 110 cases were due to vaccine-matched H3N2 viruses) were 86% (95% confidence interval [CI], 74 to 93) for the MF59-adjuvant vaccine (ATIV) and 43% (95% CI, 15 to 61) for the vaccine without the adjuvant (TIV); the relative vaccine efficacy rate for ATIV versus TIV was 75% (95% CI, 55 to 87). The efficacy rates for ATIV were 79% (95% CI, 55 to 90) in children 6 to less than 36 months of age and 92% (95% CI, 77 to 97) in those 36 to less than 72 months of age, as compared with 40% (95% CI, -6 to 66) and 45% (95% CI, 6 to 68), respectively, for TIV. Antibody responses were higher with ATIV and remained so through day 181. The rates of systemic and local reactions to the influenza vaccines with and without the adjuvant were similar in the younger age group (relative risk, 1.04; 95% CI, 0.98 to 1.09), but systemic events in the older age group were more frequent after administration of ATIV (63%) than after administration of TIV (44%) or the control vaccine (50%). Serious adverse events were distributed evenly across the three vaccine groups. CONCLUSIONS: Influenza vaccine with the MF59 adjuvant is efficacious against PCR-confirmed influenza in infants and young children. (Funded by Novartis Vaccines and Diagnostics; ClinicalTrials.gov number, NCT00644059.).

Immune response to conjugated meningococcal C vaccine in pediatric oncology patients.

BACKGROUND: Following outbreaks of meningococcal disease in Quebec in 1991-1993 and 2000-2001, a mass vaccination campaign was performed. In 2001-2002, children aged 2 months to 20 years were immunized with the Meningococcal CRM197 vaccine (Menjugate). We examined the response of pediatric oncology patients during or following maintenance chemotherapy and post-bone-marrow transplantation to Meningococcal C vaccine. PROCEDURE: This was an open label descriptive study of a cohort of patients from the oncology clinic at the Montreal Children's Hospital. A positive vaccine response was defined as a fourfold increase in specific IgG from baseline and a bactericidal assay using human complement (hBCA) titer >1:4. RESULTS: Of the 25 patients with ALL, 13 had a serologic response (average 60-fold increase). The serologic responders had a higher mean B cell count (0.262) compared to non-responders 0.068 x 10.9/L [t(23) = 2.843 (P < 0.05)]. Eleven of the 12 non-responders and 4 of the responders were on maintenance chemotherapy. In addition, two of the five patients post-bone-marrow transplant, responded. Fifteen of the 34 patients (44%) had an adequate hBCA response (mean titer 61). The group included 14/18 serologic responders with hBCA response (P < 0.001) and 16/17 non-serologic responders with no hBCA response (P < 0.001). CONCLUSIONS: Meningococcal C-conjugate vaccine produced variable responses in children with common cancers. Proximity to chemotherapy and total B cell number may help predict likelihood of response.

Reactive nitrogen intermediates in giant cell arteritis: selective nitration of neocapillaries.

Arterial wall damage in giant cell arteritis (GCA) is mediated by several different macrophage effector functions, including the production of metalloproteinases and lipid peroxidation. Tissue-invading macrophages also express nitric oxide synthase (NOS)-2, but it is not known whether nitric oxide-related mechanisms contribute to the disease process. Nitric oxide can form nitrating agents, including peroxynitrite, a nitric oxide congener formed in the presence of reactive oxygen intermediates. Protein nitration selectively targets tyrosine residues and can result in a gain, as well as a loss, of protein function. Nitrated tyrosine residues in GCA arteries were detected almost exclusively on endothelial cells of newly formed microcapillaries in the media, whereas microvessels in the adventitia and the intima were spared. Nitration correlated with endothelial NOS-3 expression and not with NOS-2-producing macrophages, which preferentially homed to the hyperplastic intima. The restriction of nitration to the media coincided with the production of reactive oxygen intermediates as demonstrated by the presence of the toxic aldehyde, 4-hydroxynonenal. Depletion of tissue-infiltrating macrophages in human temporal artery-SCID mouse chimeras disrupted nitrotyrosine generation, demonstrating a critical role of macrophages in the nitration process that targeted medial microvessels. Thus, protein nitration in GCA is highly compartmentalized, reflecting the production of reactive oxygen and reactive nitrogen intermediates in the inflamed arterial wall. Heterogeneity of microvessels in NOS-3 regulation may be an additional determinant contributing to this compartmentalization and could explain the preferential targeting of newly generated capillary beds.