SARS-CoV-2 Delta variant poised to acquire complete resistance to wild-type spike vaccines

 Yafei Liu, Noriko Arase, Jun-ichi Kishikawa, Mika Hirose, Songling Li, Asa Tada, Sumiko Matsuoka, Akemi Arakawa, Kanako Akamatsu, Chikako Ono, Hui Jin, Kazuki Kishida, Wataru Nakai, Masako Kohyama, Atsushi Nakagawa, Yoshiaki Yamagishi, Hironori Nakagami, Atsushi Kumanogoh,  

View ORCID ProfileYoshiharu Matsuura, Daron M. Standley, Takayuki Kato, Masato Okada, Manabu Fujimoto,  View ORCID ProfileHisashi Arase

doi: https://doi.org/10.1101/2021.08.22.457114

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.08.22.457114v1.full.pdf

Abstract

mRNA-based vaccines provide effective protection against most common SARS-CoV-2 variants. However, identifying likely breakthrough variants is critical for future vaccine development. Here, we found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies. Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity. Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta 4+ variant without enhancing infectivity. Given the fact that a Delta variant with three similar RBD mutations has already emerged according to the GISAID database, it is necessary to develop vaccines that protect against such complete breakthrough variants.

Competing Interest Statement

Osaka University has filed a patent application for the enhancing antibodies. HA and YL are listed as inventors. HA is a stockholder of HuLA immune Inc.

https://www.biorxiv.org/content/10.1101/2021.08.22.457114v1