A megadiverse naïve library derived from numerous camelids for efficient and rapid development of VHH antibodies

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review

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Author(s)

  • Meiniang Wang
  • Haitao Xiang
  • Bingzhao Ren
  • Xiaopan Liu
  • Lin Jiang
  • Naibo Yang

Detail(s)

Original languageEnglish
Article number114871
Journal / PublicationAnalytical Biochemistry
Volume657
Online published12 Sep 2022
Publication statusPublished - 15 Nov 2022

Abstract

The field of antibody development is under pressure to meet rising demands for speed, cost-effectiveness, efficacy, reliability, and large-scale production. It is costly and time-consuming to immunize animals and build a single-domain antibody (sdAb) library for each target. Using the variable domain (VHH) of heavy-chain only antibodies (HcAbs) derived from blood samples of 75 non-immunized camelid animals (51 alpacas, 13 llamas, 11 Bactrian camels), and spleens from two Bactrian camels, a naïve sdAb library with extensive megadiversity and reusability was constructed. The library was evaluated using next-generation DNA sequencing (NGS) and was found to contain hundreds of billions of unique clones. To confirm the availability of target-specific VHHs, a naive library was screened for a variety of targets. At least two VHH candidates were extracted for each target using a 20-day selection pipeline. Some binders had ultrahigh potencies, with binding affinities in the nanomolar range. This naïve library, in particular, offers the possibility of acquiring unique antibodies targeting antigens of interest with low feasible dissociation constant (kD) without the time, effort, and price associated in producing antibodies in animals via antigen injection. Overall, the study shows that the megadiverse naïve library provides a rapid, adaptable, and easy platform for antibody creation, emphasizing its therapeutic and diagnostic implications.

Research Area(s)

  • Heavy-chain only antibodies, Naïve VHH displaying library, Next-generation sequencing, Single-domain antibody, VHH antibody discovery platform

Citation Format(s)

A megadiverse naïve library derived from numerous camelids for efficient and rapid development of VHH antibodies. / Wang, Meiniang; Wei, Likun; Xiang, Haitao; Ren, Bingzhao; Liu, Xiaopan; Jiang, Lin; Yang, Naibo; Shi, Jiahai.

In: Analytical Biochemistry, Vol. 657, 114871, 15.11.2022.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalpeer-review