Association of dengue infection with anti-alpha-gal antibodies, IgM, IgG, IgG1, and IgG2

Abstract

Dengue virus (DENV) transmitted by the Aedes mosquitoes is the etiological agent of dengue fever, one of the fastest-growing reemerging mosquito-borne diseases on the planet with a 30-fold surge in the last five decades. Interestingly, many arthropod-borne pathogens, including DENV type 2, have been reported to contain an immunogenic glycan galactose-alpha1,3-galactose (alpha-Gal or aGal). The aGal molecule is a common oligosaccharide found in many microorganisms and in most mammals, except for humans and the Old-World primates. The loss of aGal in humans is considered to be an evolutionary innovation for enabling the production of specific antibodies against aGal that could be presented on the glycan of pathogens. The objective of this study was to evaluate different anti-aGal antibodies (IgM, IgG, IgG1, and IgG2) in people exposed to DENV. We observed a significant difference in anti-aGal IgG and IgG1 levels among dengue severity classifications. Furthermore, a significant positive correlation was observed between the anti-aGal IgG and the number of days with dengue symptoms in patients. Additionally, both anti-aGal IgM and IgG levels differ between the two geographical locations of patients. While the anti-aGal IgM and IgG2 levels were not significantly different according to the dengue severity levels, age was negatively correlated with anti-aGal IgM and positively correlated with anti-aGal IgG2. Significant involvement of aGal antibodies in Dengue infection processes is suggested based on the results. Our results open the need for further studies on the exact roles and the mechanisms of the aGal antibodies in Dengue infection.

Little disease but lots of bites: social, urbanistic, mobility, and entomological risk factors of human exposure toAedes aegyptiin South Texas, U.S.

“…aegypti peptide Nterm-34kDa (39) were synthesized by Genscript (Piscataway, NJ, USA). ELISA conditions were standardized as described elsewhere (27,30). Briefly, dried blood samples were prepared by punching a 6mm circle out of the Whatman® 903 protein saver card (GE Healthcare, US), and eluting it into 500 µL of elution buffer (PBS 1×) and incubating overnight at 4 °C.…”

“…It has been shown that for different mosquito species the use of IgG antibody response to salivary gland proteins can serve as effective indicators of human-vector contact as an exposure biomarker (23,(27)(28)(29). Moreover, high bite exposure measured via this method has been linked to disease levels in humans for both the malaria (27,28) and dengue systems (25,30) indicating its usefulness in assessing mosquito-borne disease risk. IgG antibodies are used over IgM as their specificity is greater (25), and is specific to the genus level, with some cross-reactivity between Ae.…”

Impact of the microbiome on mosquito-borne diseases

“…If similar responses could be elicited in humans, vaccination with a commensal microbe could produce antibodies against Plasmodium . However, caution is warranted in areas where both malaria and dengue fever are prevalent, as a recent study found that high levels of anti-α-gal IgG and IgG1 were associated with severe dengue fever ( Olajiga et al, 2022 ). Therefore, the application of vaccination against α-gal requires further investigation to fully understand the role of α-gal antibodies in arboviral infection.…”