Long lived multi-isotype anti-HIV antibody responses following a prime-double boost immunization strategy

Despite decades of work, an effective HIV vaccine remains elusive. In an effort to elicit protective immunity, investigators have sought to define vaccines able to elicit durable HIV-specific B-cell and T-cell activities. Additionally, vaccines are sought which can induce antibodies of a variety of isotypes, as each isotype possesses unique attributes in terms of opsonization, Fc receptor binding capacity, complement fixation and location. One prominent new vaccine strategy, applied to numerous distinct antigenic systems is the prime boost-regimen, with DNA, vaccinia virus (VV), and/or purified recombinant protein. To examine the durability, location and isotype distribution of responses induced by prime-boost regimens, we tested successive immunizations with DNA, VV and protein (D-V-P), comparing three forms of protein inoculations: (i) purified protein administered intramuscularly with complete Freunds adjuvant, (ii) purified protein administered intranasally, and (iii) purified protein conjugated to oxidized mannan, administered intranasally. We found that all three protocols elicited serum antibodies of multiple isotypes, with serum IgA being most prominent among mice immunized with mannan-conjugated protein. All D-V-P protocols, regardless of protein form or route, also elicited antibody responses at mucosal surfaces. In bronchoalveolar lavage, a tendency toward IgA production was again most prominent in mice boosted with the protein–mannan conjugate. Both B-cell and T-cell responses were sustained for more than 1 year post-immunization following each form of vaccination. Contemporaneous with long-lasting serum and mucosal antibodies were antibody forming cells in the bone marrow of primed animals. Results highlight the D-V-P vaccination strategy as a promising approach for attaining durable, multi-isotype B-cell and T-cell activities toward HIV.

Complications associated with operative fixation of acute midshaft clavicle fractures

The aim of this study was to review the complication rate and profile associated with surgical fixation of acute midshaft clavicle fracture in a large cohort of patients treated in a level I trauma centre.Patients and methods: We identified all patients who underwent surgical treatment of acute midshaft clavicle fracture between 2002 and 2010. The study group consisted of 138 fractures (134 patients). There were 107 males (78%) and 31 females (22%) and median age of 35 years (IQR 24-45). The most common mechanism of injury was a road traffic accident (78%). Sixty percent (n = 83) had an injury severity score of ≥ 15 indicating major trauma. The most common fracture type (75%) was simple or wedge comminuted (2B1) according to the Edinburgh classification. The median interval between the injury and operation was 3 days (IQR 1-6). Plate fixation was performed in 110 fractures (80%) and intramedullary fixation was performed in 28 fractures (20%). There were 85 males and 25 females in the plate fixation group with median age of 35 years (IQR: 25-45) There were 22 males and 6 females in intramedullary fixation group with median age of 31 years (IQR 24-42 years). Statistical analysis was performed using Independent sample t-test, Mann-Whitney test, and Chi-square test. Significant P-value was < 0.05.Results: The overall incidence of complication was 14.5% (n = 20). The overall nonunion rate 6%. Post operative wound infection occurred in 3.6% of cases. The incidence of complication associated with plate fixation was 10% (11 of 110 cases) compared to 32% associated with intramedullary fixation (9 of 28 cases) (P = 0.003). Thirty five percent of complications were related to inadequate surgical technique and potentially avoidable. Symptomatic hardware requiring removal occurred in 23% (n = 31) of patients. Symptomatic metalware was more frequent after plate fixation compared to intramedullary fixation (26% vs 7%, P = 0.03).Conclusions: Intramedullary fixation of midshaft clavicle fracture is associated with higher incidence of complications. Plate fixation is associated with a higher rate of symptomatic metalware requiring removal compared to intramedullary fixation. Approximately one in three complications may be avoided by attention to adequate surgical technique.