How Do Antibodies Work Against Zika Virus
A previous study published by PNAS stated 'recent epidemics demonstrate the global threat of Zika virus, a flavivirus transmitted by mosquitoes. There are concerns for designing a safe vaccine for the Zika virus because antibodies (Abs) elicited against Zika may also bind flaviviruses that share a similar envelope protein.
If Abs elicited by a Zika vaccine bind but do not effectively neutralize other flaviviruses, they may enhance virus entry into cells through the process of Ab-dependent enhancement of infection, potentially leading to more severe disease.
By directly comparing how mature Zika-neutralizing Abs and their germline precursors bind different flaviviruses, these researchers provide insights into the Ab maturation process and the molecular interactions important for strong, neutralizing binding to Zika versus weak, cross-reactive binding to other flaviviruses.
To better understand the neutralizing Ab response and risk of Ab-dependent enhancement, further information on germline Ab binding to ZIKV and the maturation process that gives rise to potently neutralizing Abs is needed.
This study used binding and structural studies to compare mature and inferred-germline Ab binding to envelope protein domain III of ZIKV and other flaviviruses. It shows that the light-chain variable domain's affinity maturation is important for strong binding of the recurrent VH3-23/VK1-5 neutralizing Abs to ZIKV envelope protein domain III and identify interacting residues that contribute to weak, cross-reactive binding to West Nile virus.
These findings provide insight into the affinity maturation process and potential cross-reactivity of VH3-23/VK1-5 neutralizing Abs, informing precautions for protein-based vaccines designed to elicit germline versions of neutralizing Abs.