Naturally acquired immune responses to alpha-gal in malaria endemic settings and pre-clinical efficacy testing with R21/MM

Résumé fourni par la source

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 ). • Naturally induced anti- Alpha-gal (α-gal) IgG and IgM antibodies can be detected in infants and adults from malaria endemic regions. • There is a negative correlation seen between levels of anti- α-gal IgM antibody levels and malaria episodes in malaria-endemic region Burkina Faso 5–17-month infants. • BSA-linked α-gal with adjuvant Matrix-M induced IgG and IgM responses in α-gal transferase knock out (α1,3GT KO) mice but failed to protect against sporozoite challenge.

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