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High temperature selection of nucleotide-supported carbohydrate vaccines and resulting glycosylated oligonucleotides
About
As an optimization of the original SELMA method, we achieved dramatically stronger target recognition (100-fold) with fewer glycans (2-3 fold). Compared to the previous application of SELMA, the current glycoclusters contain fewer glycans (3-4 vs. 5-10 in the past), yet bind to the 2G12 HIV antibody target with Kd’s as low as 1.7 nM (vs. 150- 500 nM Kd’s in the past). These glycoclusters are recognized by 2G12 as tightly as is the HIV envelope protein gp120, and they are the first constructs to achieve this tight recognition with the minimal number of Man9 units (3-4) necessary to occupy the binding sites on 2G12. They are thus of interest as immunogens that might elicit broadly neutralizing antibodies against HIV. The invention shows that SELMA-based glycocluster selection, with the temperature increased to 37 °C, affords low-valent Man9 clusters whose affinity for 2G12 matches that of gp120 both thermodynamically and kinetically. The high temperature 37°C selection winners are not only of higher affinity (1.7-16 nM vs 150-500 nM) but also contain fewer glycans than room temperature selection winners (3-5 vs 7-10)
Key Benefits
•An optimized method to generate carbohydrate-oligonucleotide conjugates to produce HIV vaccine at 37°C •High temperature selection affords higher affinity and contains fewer glycans than room temperature •A successful strategy for biotech/pharmaceuticals based on exhaustive antigen epitope space