Mukhopadhyay ES, Bellamy DG, Tinto H, Hamaluba M, Truby A, et al.
Vaccine •
Malaria sporozoite surface glycan alpha-gal (α-gal), which is absent in humans has been shown to elicit an antibody response that can confer protection against malaria in alpha- gal transferase knock- out mice. In humans, several studies have highlighted association of antibodies to this glycan with protection against malaria in endemic regions. Here, we first assess the anti- α-gal IgG and IgM antibody levels in serum samples obtained from sporozoite challenged malaria naïve UK volunteers, and naturally exposed or infected Kenyan adults and Burkina Faso infants. In UK volunteers, there was no significant increase seen in antibody levels 90 days post challenge. We observe increases in anti- α-gal IgG and IgM antibodies over time only in Burkina Faso infants. In Burkina Faso infants, protection from malaria could be correlated to higher anti- α-gal IgM antibody levels and possibly to anti- α-gal IgG antibody levels. We then evaluate Bovine Serum Albumin (BSA) linked α-gal with highly potent adjuvant Matrix-M (MM) for immunogenicity and efficacy in alpha- gal transferase knock-out (α1,3GT KO) mice. BSA-linked α-gal elicits an IgG and IgM response but failed to protect against the sporozoite challenge. Clinical trials registry: VAC049 (NCT01465048), VAC073 (NCT03580824), VAC076 (NCT03896724).
Commins SP, Kelly LA, Rönmark E, James HR, Pochan SL, et al.
American journal of respiratory and critical care medicine •
IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract. To evaluate the relationship between IgE antibodies to α-gal and asthma, and compare this with the relationship between asthma and IgE antibodies to Fel d 1 and other protein allergens. Patients being investigated for recurrent anaphylaxis, angioedema, or acute urticaria underwent spirometry, exhaled nitric oxide, questionnaires, and serum IgE antibody assays. The results were compared with control subjects and cohorts from the emergency department in Virginia (n = 130), northern Sweden (n = 963), and rural Kenya (n = 131). Patients in Virginia with high-titer IgE antibodies to α-gal had normal lung function, low levels of exhaled nitric oxide, and low prevalence of asthma symptoms. Among patients in the emergency department and children in Kenya, there was no association between IgE antibodies to α-gal and asthma (odds ratios, 1.04 and 0.75, respectively). In Sweden, IgE antibodies to cat were closely correlated with IgE antibodies to Fel d 1 (r = 0.83) and to asthma (P < 0.001). These results provide a model of an ectoparasite-induced specific IgE response that can increase total serum IgE without creating a risk for asthma, and further evidence that the main allergens that are causally related to asthma are those that are inhaled.
Commins SP, James HR, Kelly LA, Pochan SL, Workman LJ, et al.
The Journal of allergy and clinical immunology •
In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-α-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur. Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP. Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20-fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (χ(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001). The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.