Synergistic Effect of Two Nanotechnologies Enhances the Protective Capacity of the Theileria parva Sporozoite p67C Antigen in Cattle

Multimerization of p67C Ag as nanoparticle increases its immunogenicity.Vaccine efficacy of p67C Ag increases delivered as nanoparticles.East Coast fever (ECF), caused by Theileria parva, is the most important tick-borne disease of cattle in sub-Saharan Africa. Practical disadvantages associated with the currently used live-parasite vaccine could be overcome by subunit vaccines. An 80-aa polypeptide derived from the C-terminal portion of p67, a sporozoite surface Ag and target of neutralizing Abs, was the focus of the efforts on subunit vaccines against ECF and subjected to several vaccine trials with very promising results. However, the vaccination regimen was far from optimized, involving three inoculations of 450 μg of soluble p67C (s-p67C) Ag formulated in the Seppic adjuvant Montanide ISA 206 VG. Hence, an improved formulation of this polypeptide Ag is needed. In this study, we report on two nanotechnologies that enhance the bovine immune responses to p67C. Individually, HBcAg-p67C (chimeric hepatitis B core Ag virus-like particles displaying p67C) and silica vesicle (SV)–p67C (s-p67C adsorbed to SV-140-C18, octadecyl-modified SVs) adjuvanted with ISA 206 VG primed strong Ab and T cell responses to p67C in cattle, respectively. Coimmunization of cattle (Bos taurus) with HBcAg-p67C and SV-p67C resulted in stimulation of both high Ab titers and CD4 T cell response to p67C, leading to the highest subunit vaccine efficacy we have achieved to date with the p67C immunogen. These results offer the much-needed research depth on the innovative platforms for developing effective novel protein-based bovine vaccines to further the advancement

Immune parameters to p67C antigen adjuvanted with ISA206VG correlate with protection against East Coast fever

East Coast fever (ECF) is a lymphoproliferative disease caused by the tick-transmitted protozoan parasite Theileria parva. ECF is one of the most serious cattle tick-borne diseases in Sub-Saharan Africa. We have previously demonstrated that three doses of the C-terminal part of the sporozoite protein p67 (p67C) adjuvanted with ISA206VG confers partial protection against ECF at a herd level. We have tested the efficacy of two doses of this experimental vaccine, as reducing the vaccination regimen would facilitate its deployment in the field. We reconfirm that three antigen doses gave a significant level of protection to severe disease (46%, ECF score < 6) when compared with the control group, while two doses did not (23%). Animals receiving three doses of p67C developed higher antibody titers and CD4+ T-cell proliferation indices, than those which received two doses. A new panel of immune parameters were tested in order to identify factors correlating with protection: CD4+ proliferation index, total IgG, IgG1, IgG2 and IgM half maximal titers and neutralization capacity of the sera with and without complement. We show that some of the cellular and humoral immune responses provide preliminary correlates of protection

Cortisol awakening response and developmental outcomes at 6–7 years in children born extremely preterm

BackgroundExtremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.MethodsThis secondary analysis of a sub-cohort of the SUPPORT study included children born between 24 and 27 weeks, evaluated at 6-7 years with a neurodevelopmental battery and cortisol measures. Differences were tested between EPT and a term-born group. Relationships of cortisol awakening response to test scores were analyzed.ResultsCortisol was measured in 110 EPT and 29 term-born 6-7 year olds. Unadjusted WISC-IV and NEPSY-II scores were significantly worse among EPT children only. Conners Parent Rating Scale behavior scores were significantly worse among EPT children. After adjusting for covariates, blunted cortisol awakening responses were found to be associated with poorer scores on memory tests and greater problems with inattention for the EPT group (p &lt; 0.05) only.ConclusionsAmong children born EPT, we identified an association of blunted cortisol awakening response with memory and inattention problems. This may have implications related to stress reactivity and its relationship to learning problems in children born EPT.ClinicaltrialsGov idExtended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort: NCT00233324.ImpactIn children born EPT, stress reactivity may have a relationship to learning problems. Cortisol awakening response should be a component for follow-up in EPT born children. Components of executive function, such as memory and attention, are related to stress reactivity