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Vaccines have been the single most significant advancement in public health, preventing morbidity and mortality in millions of people annually. Vaccine development has traditionally focused on whole organism vaccines, either live attenuated or inactivated vaccines. While successful for many different infectious diseases whole organisms are expensive to produce, require culture of the infectious agent, and have the potential to cause vaccine associated disease in hosts. With advancing technology and a desire to develop safe, cost effective vaccine candidates, the field began to focus on the development of recombinantly expressed antigens known as subunit vaccines. While more tolerable, subunit vaccines tend to be less immunogenic. Attempts have been made to increase immunogenicity with the addition of adjuvants, either immunostimulatory molecules or an antigen delivery system that increases immune responses to vaccines. An area of extreme interest has been the application of nanotechnology to vaccine development, which allows for antigens to be expressed on a particulate delivery system. One of the most exciting examples of nanovaccines are rationally designed protein nanoparticles. These nanoparticles use some of the basic tenants of structural biology, biophysical chemistry, and vaccinology to develop protective, safe, and easily manufactured vaccines. Rationally developed nanoparticle vaccines are one of the most promising candidates for the future of vaccine development., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Concerns about the very small, but real risk of anaphylaxis after vaccination, has given rise to specific questions about the safe administration of vaccines to children and adolescents in the context of preventive settings (i.e. well baby clinics and school health services). As a support to preventive health professionals a guideline based on scientific evidence and supported by professional consensus was developed in Belgium., Methods: First, a draft of guideline was written based on a review of international literature. Second, through several rounds of consultation professional consensus about the document was obtained across the Belgian communities and professional groups, and in a final version endorsed by the Belgian Superior Health Council in July 2012., Results: In a literature overview information is given about the definition of anaphylaxis, allergens in vaccines potentially causing anaphylaxis, published incidence rates of anaphylaxis after vaccination, and strategies for first-aid management of anaphylaxis. The Belgian guideline on the prevention of anaphylaxis after vaccination includes recommendations on prevaccination risk assessment, the content of the emergency kit, measures to be taken after vaccination, differential diagnosis and first-aid management of anaphylaxis., Conclusion: The guideline, summarized as a flowchart for the prevention and first-aid management of anaphylaxis, is considered as the actual state of the art in Belgium for vaccination of children and youngsters in preventive health services, and may inspire governmental bodies and/or professional groups in other countries to adopt similar recommendations., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Modulation of the inflammatory response through vaccination has shown promise in animal models of atherogenesis and obesity-main risk factors for cardiovascular diseases. Tableted preparation, V-6, containing pooled antigens derived from pig adipose tissue was administered per os daily to 13 volunteers for 3 months. Total cholesterol and LDL levels have not changed from the baseline value; 193.4 vs 191.8 (p=0.75) and 113.8 vs 117.2 (p=0.18), respectively. Triglyceride levels declined by 26.1% from 163 to 120.5mg/dL (p=0.29). HDL increased by 25.9% from 38.6 to 48.5mg/dL (p=0.000002) in 12 out 13 patients. Despite negligible effect of V6 on weight and body mass index, i.e., 67.87 vs 66.58 kg (-1.9%; p=0.46) and 26.25 vs 25.75 kg/m(2) (-1.9%; p=0.35), statistically significant reduction in waist (-7.6%; p=0.002), mid-arm (-3.3%; p=0.049), and thigh (-7.6%; p=0.0003) circumferences were observed. Blood pressure systolic and diastolic values were not affected, i.e., 115.6 vs 121 (p=0.2) and 77.1 vs 83 (p=0.55). No changes were observed in liver ALT and AST enzymes. Creatinine decreased; 0.877 vs 0.842 mg/dL (p=0.02), while BUN has shown slight increase; 14.8 vs 16.1mg/dL (p=0.03) but within normal range. Fasting blood sugar levels were also within normal range, i.e., 94.8 vs 98.8 (p=0.04). Complete blood cell analysis has not revealed any change except slight decrease in hemoglobin 13.25-13.19 g/dL (p=0.0004), but its amount per red blood cell (MCH) increased from 25.62 up to 26.42 picograms/cell (p=0.000003). The average red blood cell size (MCV) increased from 78.5 to 80.0 fl (p=0.00009) but hemoglobin concentration relative to size of the cell (MCHC) has not changed (p=0.2). Hematocrit and red blood cells count decreased slightly, but within normal range 40.7-40.2% (p=0.02) and 5.22-5.05 x 10(6)cells/mm(3) (p=0.002). The number of platelets moved upward, 2.471 vs 2.921 x 10(5)per mm(3) (p=0.009). The white blood cells count and percent of leukocytes and neutrophils were not affected. Pro-inflammatory eosinophils declined from 4.0% down to 2.4% (p=0.29). These results show that V6 is safe and holds a promise as an anti-atherogenic and overweight/obesity immune intervention., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Purpose: To determine the duration of action of ketotifen 0.025% eye drops vs placebo taken as single or multiple doses in an allergen challenge model., Design: Two randomized, multicenter, double-masked, contralateral placebo-controlled studies, one a single-dose and one a multiple-dose study., Methods: Two conjunctival provocation tests (CPTs) were initially conducted to confirm reproducibility of subject responses in both studies. Subjects in study 1 (n = 87) received single doses of ketotifen in one eye and placebo in the other 15 minutes, 6 hours, and 8 hours before CPT. Subjects in study 2 (n = 85) received ketotifen or placebo once 8 hours before CPT. Single-dose efficacy results were used to further qualify a subject as a responder. Responders were re-randomized to a 4-week twice daily dosing regimen with a CPT 8 hours after the final dose. In both studies, ocular symptoms were assessed at three time points 3 to 15 minutes after challenge. There were no significant differences in adverse events between groups., Results: For both studies, ocular itching and vascular injection were significantly reduced (P <.003) at all time points after instillation of ketotifen, with a maximum reduction at 7 minutes postchallenge. In study 2, chemosis, tearing, and lid swelling were also assessed and were significantly reduced (P <.008) after instillation of ketotifen., Conclusions: Ketotifen 0.025% eye drops were safe and statistically effective in preventing ocular itching, injection, and other signs and symptoms of allergic conjunctivitis at 15 minutes, 6 hours, and 8 hours after a single dose and at 8 hours after the final dose of a 4-week twice daily regimen.

Purpose: To evaluate the effect and safety of the oral administration of retinal antigens as a treatment of ocular inflammation., Methods: In a phase I/II randomized masked trial, patients with endogenous uveitis who were dependent on immunosuppressive agents were randomly assigned to receive either retinal S antigen alone (10 patients), retinal S antigen and a mixture of soluble retinal antigens (10 patients), a mixture of soluble retinal antigens alone (10 patients), or placebo (15 patients). An attempt was then made to taper patients completely off their standard immunosuppressive therapy over an 8 week period. The primary study endpoint was time to ocular inflammatory attack. The secondary study endpoint was the ability to taper patients completely off their immunosuppressive or cytotoxic medication within 8 weeks., Results: Time to development of the main study endpoint was not statistically significantly different for any of the four treatment groups. However, the group receiving the purified S antigen alone appeared to be tapered off their immunosuppressive medication more successfully compared with patients given placebo (P = .08), whereas all the other groups appeared to do worse than did those receiving placebo. No toxic effects attributable to any treatment were observed., Conclusions: This phase I/II study is the first to test the use of orally administered S antigen in the treatment of uveitis. Although not statistically significant, patients given S antigen were more likely to be tapered off their chronically administered systemic immunosuppressive therapy than were the other groups tested.

The effects of calcium channel blockers, nifedipine and verapamil (i.v. and aerosol), were investigated in beagle dogs natively allergic to Ascaris suum antigen. Control exposures to an aerosol of Ascaris antigen provoked significant bronchopulmonary changes, i.e., increases in pulmonary resistance (RL) and decreases in dynamic lung compliance (CDYN). Pretreatment with either nifedipine or verapamil (200 micrograms/kg, i.v.) provided significant inhibition in the RL responses to Ascaris antigen (P less than 0.015) while neither agent significantly affected CDYN changes. When administered as an aerosol, verapamil (1.0%; 10 breaths) significantly inhibited both the RL and CDYN responses to Ascaris antigen (P less than 0.05), whereas a similar concentration of nifedipine was without effect. Resting basal levels of RL and CDYN were unaffected by either the i.v. route or by aerosols of either nifedipine or verapamil. These results suggest that calcium channel blockers may have beneficial effects against allergen-provoked bronchoconstriction; however, differences appear to exist in the choice of agent, route of administration and site of action.