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Progress in HIV-1 Vaccine Development

Advances in HIV vaccine development have been hampered by roadblocks associated with failure to prevent infection. In recent years, a number of basic and translational science advances have shown promise in the development for an effective vaccine. In their review, Haynes and colleagues summarize these advances along with the roadblocks that still remain, as well as the most promising approaches to successful vaccine design ( J Allergy Clin Immunol 2014, 134(1): 3-10 ).  This year, the field of HIV-vaccine research had a major disappointment in the announcement of the lack of a vaccine efficacy seen in a DNA prime, recombinant adenovirus type 5 (rAd5) boost HIV-1 vaccine trial developed by the NIH Vaccine Research Center. The vaccine was designed to test the hypothesis that high levels of CD8+ cytotoxic T cells (CTLs) could either protect against transmission or lead to control of plasma HIV-1 viral load. The second failed trial, the Merck recombinant adenovirus type 5 trail, not o...

Prenatal exposure to diesel exhaust induces asthma susceptibility through NK cell priming

Asthma often begins early in life and is attributed to more than just genetic factors, because the prevalence continues to rise. Epidemiological studies have indicated roles for prenatal and early childhood exposures, including exposure to diesel exhaust, however, little is known about the mechanisms involved. To elucidate this, Manners et al developed a mouse model of asthma susceptibility through prenatal exposure to diesel exhaust ( J Allergy Clin Immunol 2014; 134(1): 63-72 ) . In this model, pregnant mice were repeatedly exposed to diesel exhaust particles (DEPs). Offspring were immunized and challenged with ovalbumin (OVA) or exposed to PBS (control) then examined for features of asthma. Compared to controls, offspring that were exposed to DEP were hypersensitive to OVA, indicated by airway hyperresponsiveness, elevated serum levels of OVA-specific IgE, and elevated levels of pulmonary and systemic T-helper type 2 (Th2) and Th17 cytokines. The authors determined that natural kill...

The effects of calcitriol treatment in glucocorticoid resistant asthma

The current and most effective treatment for asthma therapy is the use of glucocorticoids by improving the clinical features and airway inflammation associated with asthma. However, a cohort of well-defined asthma patients exists in whom high-dose glucocorticoid treatment is not only clinically ineffective, but potentially detrimental.  Several mechanisms have been proposed to contribute to glucocorticoid resistance, including vitamin D insufficiency. Nanzer et al recently published data that glucocorticoid resistant patients fail to synthesize the anti-inflammatory cytokine interleukin-10 (IL-10) in response to glucocorticoid in vitro compared to glucocorticoid sensitive patients ( J Allergy Clin Immunol 2014; 133(6): 1755-1757 ). When resistant patients ingested a form of vitamin D called calcitriol (1,25-dihydroxyvitamin D3) in combination with glucocorticoid, levels of IL-10 were restored in vivo and ex-vivo. Taken together, these data along with epidemiological evidence linkin...

Mechanisms underlying the neuronal based symptoms of allergy

People with allergies often present with symptoms that are the result of alterations in the nervous system in the organ in which the reaction occurs. Common neuronal symptoms include itchy eyes, sneezing, nasal congestion, rhinorrhea, cough, bronchoconstriction, airway mucus secretion, dysphagia, altered gastrointestinal motility, and itchy swollen skin. Mediators released during an allergic reaction interact with sensory nerves, altering the transmission of signals in the sympathetic and parasympathetic autonomic nerves. Undem and Taylor-Clark describe how the nervous system itself is altered in allergic disease either due to events occurring during critical periods of neuronal development or to persistent nerve stimulation ( J Allergy Clin Immunol 2014; 133(6): 1521-1534 ) . Those that suffer from allergic rhinitis for example, more often react strongly by sneezing when stimulants are applied to the nasal mucosa compared to healthy controls. Considering sneezing is a parasympathetic ...

Potential food allergens in medications

Excipients are all of the substances found in pharmaceuticals that are added to the active ingredient to provide a benefit in manufacturing, stability, bioavailability, or patient acceptability.  Some excipients are foods or substances derived from foods.  Food allergic patients may rarely have reactions to these products. In his review, John M. Kelso, MD details which food-derived substances are used as pharmaceutical excipients and in which medications. Furthermore, the safety of administration of these medications in food allergic patients is also discussed ( J Allergy Clin Immunol 2014; 133(6): 1509-1518 ).  Food allergens are proteins that can generate IgE-mediated responses in food-allergic individuals. Since some food-derived excipients in medications are proteins, there is potential for an allergic response.  However, in most cases there is not enough of the food protein present to cause a reaction even in an allergic individual.  For example, most influ...

Effects of antioxidants on asthma

While the prevalence of asthma and allergic diseases continues to rise, the consumption of dietary antioxidants is decreasing around the world.  The western diet is becoming more popular around the world even though it is characterized by a reduction of fresh fruits and vegetables with an increase of processed foods and antioxidant enriched foods. As pulmonary and systemic oxidative stress increase allergic inflammation, dietary or supplemental antioxidants have been proposed to counteract the incidence and morbidity of allergic disease.  Moreno-Macias and Romieu summarize various studies associated with the effects of antioxidants on asthma and allergic diseases ( J Allergy Clin Immunol 2014; 133(5): 1237-44 ). Meta-analyses of epidemiologic studies of variable quality suggest associations of low dietary intake of antioxidants and increased asthma and allergy. Compared to asthma, few trials have looked at associations between diet and atopic dermatitis, allergic rhinitis, or ...

Peanut, milk and wheat intake during pregnancy is associated with reduced allergy and asthma in children

The relationship between maternal diet and childhood allergy and asthma is controversial.  Not long ago, the American Academy of Pediatrics advised that maternal dietary restrictions are not necessary with the possible exception of excluding peanuts.  Subsequent systematic reviews concluded that the evidence was inadequate to support any dietary restrictions during pregnancy. In fact, recent research suggests that fetal exposure to common food allergens may be beneficial. Bunyavanich et al examined the associations between maternal intake of common childhood food allergens during pregnancy and childhood asthma and allergies ( J Allergy Clin Immunol 2014; 133(5): 1373-1382 ).   The authors studied a healthy pre-birth cohort of 1277 mother-child pairs from the United States and used food frequency questionnaires administered during pregnancy. Children were assessed for food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum specific IgE lev...