Heterologous SARS-CoV-2 spike protein booster elicits durable and broad antibody responses against the receptor-binding domain

Tomohiro Takano, Takashi Sato, Ryutaro Kotaki, Saya Moriyama, Shuetsu Fukushi, Masahiro Shinoda, Kiyomi Kabasawa, Nagashige Shimada, Mio Kousaka, Yu Adachi, Taishi Onodera, Kazutaka Terahara, Masanori Isogawa, Takayuki Matsumura (), Masaharu Shinkai () and Yoshimasa Takahashi ()
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Tomohiro Takano: National Institute of Infectious Diseases
Takashi Sato: Tokyo Shinagawa Hospital
Ryutaro Kotaki: National Institute of Infectious Diseases
Saya Moriyama: National Institute of Infectious Diseases
Shuetsu Fukushi: National Institute of Infectious Diseases
Masahiro Shinoda: Tokyo Shinagawa Hospital
Kiyomi Kabasawa: Tokyo Shinagawa Hospital
Nagashige Shimada: Tokyo Shinagawa Hospital
Mio Kousaka: Tokyo Shinagawa Hospital
Yu Adachi: National Institute of Infectious Diseases
Taishi Onodera: National Institute of Infectious Diseases
Kazutaka Terahara: National Institute of Infectious Diseases
Masanori Isogawa: National Institute of Infectious Diseases
Takayuki Matsumura: National Institute of Infectious Diseases
Masaharu Shinkai: Tokyo Shinagawa Hospital
Yoshimasa Takahashi: National Institute of Infectious Diseases

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract The immunogenicity of mRNA vaccines has not been well studied when compared to different vaccine modalities in the context of additional boosters. Here we show that longitudinal analysis reveals more sustained SARS-CoV-2 spike receptor-binding domain (RBD)-binding IgG titers with the breadth to antigenically distinct variants by the S-268019-b spike protein booster compared to the BNT162b2 mRNA homologous booster. The durability and breadth of RBD-angiotensin-converting enzyme 2 (ACE2) binding inhibitory antibodies are pronounced in the group without systemic adverse events (AEs) after the S-268019-b booster, leading to the elevated neutralizing activities against Omicron BA.1 and BA.5 variants in the stratified group. In contrast, BNT162b2 homologous booster elicited antibodies to spike N-terminal domain in proportion to the AE scores. High-dimensional immune profiling identifies early CD16+ natural killer cell dynamics with CCR3 upregulation, as one of the correlates for the distinct anti-RBD antibody responses by the S-268019-b booster. Our results illustrate the combinational effects of heterologous booster on the immune dynamics and the durability and breadth of recalled anti-RBD antibody responses against emerging virus variants.

Date: 2023
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DOI: 10.1038/s41467-023-37128-1

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