Latvian Biomedical Research and Study Centre (BMC), Riga, Latvia.

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Latvian Biomedical Research and Study Centre (BMC), Riga, Latvia

HA2.3 story Evaluation of vaccine candidate constructs

HA stalk constructs HA2.3 ( ) is soluble when expressed alone HA2.3 (72 aa) Forms trimer (A) Resembles HA post-fusion structure (B)

HA stalk constructs HA2.6 ( ) is not soluble when expressed alone HA2.6 (124 aa) Possibly HA2.3 could mimic the whole stalk?

HA stalk constructs HA2.3 undergoes structural changes at different pH? Pre-fusion (neutral pH) Post-fusion (low pH) Xu and Wilson, 2011

HA stalk constructs NMR analysis of HA2.3 suggests structural changes at different pH pH8=red pH7=orange pH6.2= yellow pH6.0=green pH5.5=light blue pH5.1=blue pH4.6=violet

Chemical coupling Incorporation of HA2.3 into VLPs 1.Qb VLPs 2.Qb VLPs+linker 3.Qb VLPs+linker+HA2.3 Qb+HA2.3 HA2.3 non-bind Low immune response?

Genetic fusion Incorporation of HA2.3 into VLPs Could naturally form trimer structure on VLPs with T=3 symmetry Phage CP (Qb, AP, PP7) HA2.3 AP-HA

Potential vaccine candidates expressed in yeast Evaluation of vaccine candidate constructs SynthesisSolubilitySalt/termo stability VLPsOuchterlonyStorage

Evaluation of vaccine candidate constructs

Summary