Immunogenicity and Safety of a Live-attenuated SARS-CoV-2 Vaccine Candidate Based on Multiple Attenuation Mechanisms

Overview

Journal Elife

Specialty Biology

Date 2025 Feb 11

PMID 39932490

Authors

Mie Suzuki Okutani

Shinya Okamura

Tang Gis

Hitomi Sasaki

Suni Lee

Akiho Kashiwabara

Simon Goto

Mai Matsumoto

Mayuko Yamawaki

Toshiaki Miyazaki

Tatsuya Nakagawa

Masahito Ikawa

Wataru Kamitani

Shiro Takekawa

Koichi Yamanishi

Hirotaka Ebina

Affiliations

Soon will be listed here.

Abstract

mRNA vaccines against SARS-CoV-2 were rapidly developed and were effective during the pandemic. However, some limitations remain to be resolved, such as the short-lived induced immune response and certain adverse effects. Therefore, there is an urgent need to develop new vaccines that address these issues. While live-attenuated vaccines are a highly effective modality, they pose a risk of adverse effects, including virulence reversion. In the current study, we constructed a live-attenuated vaccine candidate, BK2102, combining naturally occurring virulence-attenuating mutations in the , , spike, and coding regions. Intranasal inoculation with BK2102 induced humoral and cellular immune responses in Syrian hamsters without apparent tissue damage in the lungs, leading to protection against a SARS-CoV-2 D614G and an Omicron BA.5 strains. The neutralizing antibodies induced by BK2102 persisted for up to 364 days, which indicated that they confer long-term protection against infection. Furthermore, we confirmed the safety of BK2102 using transgenic (Tg) mice expressing human ACE2 (hACE2) that are highly susceptible to SARS-CoV-2. BK2102 did not kill the Tg mice, even when virus was administered at a dose of 10 plaque-forming units (PFUs), while 10 PFU of the D614G strain or an attenuated strain lacking the furin cleavage site of the spike was sufficient to kill mice. These results suggest that BK2102 is a promising live-vaccine candidate strain that confers long-term protection without significant virulence.

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