Review 1: "Characterization of an EG.5.1 Clinical Isolate In Vitro and In Vivo"

Nicholas Maness

doi:doi:10.1162/2e3983f5.4f8cd265

Characterization of an EG.5.1 clinical isolate in vitro and in vivo

by Ryuta Uraki, Maki Kiso, Kiyoko Iwatsuki-Horimoto, Seiya Yamayoshi, Mutsumi Ito, Shiho Chiba, Yuko Sakai-Tagawa, Masaki Imai, Yukie Kashima, Michiko Koga, Noriko Fuwa, Nobumasa Okumura, Masayuki Hojo, Noriko Iwamoto, Hideaki Kato, Hideaki Nakajima, Norio Ohmagari, Hiroshi Yotsuyanagi, Yutaka Suzuki, and Yoshihiro Kawaoka

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Published on Sep 01, 2023
www.biorxiv.org

Description

Abstract EG.5.1 is a subvariant of the SARS-CoV-2 Omicron XBB variant that is rapidly increasing in prevalence worldwide. EG.5.1 has additional substitutions in its spike protein (namely, Q52H and F456L) compared with XBB.1.5. However, the pathogenicity, transmissibility, and immune evasion properties of clinical isolates of EG.5.1 are largely unknown.In this study, we used wild-type Syrian hamsters to investigate the replicative ability, pathogenicity, and transmissibility of a clinical EG.5.1 isolate. Our data show that there are no obvious differences in growth ability and pathogenicity between EG.5.1 and XBB.1.5, and both EG.5.1 and XBB.1.5 are attenuated compared to a Delta variant isolate.We also found that EG.5.1 is transmitted more efficiently between hamsters compared with XBB.1.5. In addition, unlike XBB.1.5, we detected EG.5.1 virus in the lungs of four of six exposed hamsters, suggesting that the virus tropism of EG.5.1 is different from that of XBB.1.5 after airborne transmission.Finally, we assessed the neutralizing ability of plasma from convalescent individuals and found that the neutralizing activity against EG.5.1 was slightly, but significantly, lower than that against XBB.1.5 or XBB.1.9.2. This suggests that EG.5.1 effectively evades humoral immunity and that the amino acid differences in the S protein of EG.5.1 compared with that of XBB.1.5 or XBB.1.9.2 (i.e., Q52H, R158G, and F456L) alter the antigenicity of EG.5.1.Our data suggest that the increased transmissibility and altered antigenicity of EG.5.1 may be driving its increasing prevalence over XBB.1.5 in the human population.

RR:C19 Evidence Scale rating by reviewer:

Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review: The recently emerged variant EG.5 does not show increased pathogenicity relative to XBB 1.5, but does have a slightly greater ability to evade immunity and may be somewhat more transmissible.

This report is timely and important, and the studies are well executed. Suggestions that may be valuable include the following. Most variant comparisons, particularly those conducted in vivo, are between EG.5, XBB 1.5, and delta (B.1.617.2). These comparisons are important, but delta was a bit of an outlier in the pandemic, showing higher pathogenicity than prior and subsequent variants. Additional comparisons of the two newer variants against ancestral virus would provide valuable information about how the new variant behaves. Additional comparisons with the original omicron, BA.1, may also be informative, to demonstrate any altered pathogenicity due to viral evolution since BA.1 first arose. These additional experiments are not required for the presented conclusions but would help the reader interpret the data in the context of the whole pandemic. Second, the suggestion of altered tropism (greater infection in lung relative to XBB 1.5 after airborne transmission) may be premature due to the small number of animals. These data are presented as a suggestion and a statement is included that further evaluation is required, so this issue is adequately presented in the report. All in all this is an important report based on strong data.