Neither bebtelovimab nor any mAb combinations tested neutralized the SARS-CoV-2 omicron subvariants BQ.1.1 and XBB, but remdesivir, molnupiravir, and nirmatrelvir were efficacious against both in ...vitro.
In this study, investigators who were evaluating in vitro neutralization of omicron subvariants by monoclonal antibodies and antiviral drugs found considerable variation among the agents.
The recent emergence of SARS-CoV-2 Omicron (B.1.1.529 lineage) variants possessing numerous mutations has raised concerns of decreased effectiveness of current vaccines, therapeutic monoclonal ...antibodies and antiviral drugs for COVID-19 against these variants
. The original Omicron lineage, BA.1, prevailed in many countries, but more recently, BA.2 has become dominant in at least 68 countries
. Here we evaluated the replicative ability and pathogenicity of authentic infectious BA.2 isolates in immunocompetent and human ACE2-expressing mice and hamsters. In contrast to recent data with chimeric, recombinant SARS-CoV-2 strains expressing the spike proteins of BA.1 and BA.2 on an ancestral WK-521 backbone
, we observed similar infectivity and pathogenicity in mice and hamsters for BA.2 and BA.1, and less pathogenicity compared with early SARS-CoV-2 strains. We also observed a marked and significant reduction in the neutralizing activity of plasma from individuals who had recovered from COVID-19 and vaccine recipients against BA.2 compared to ancestral and Delta variant strains. In addition, we found that some therapeutic monoclonal antibodies (REGN10987 plus REGN10933, COV2-2196 plus COV2-2130, and S309) and antiviral drugs (molnupiravir, nirmatrelvir and S-217622) can restrict viral infection in the respiratory organs of BA.2-infected hamsters. These findings suggest that the replication and pathogenicity of BA.2 is similar to that of BA.1 in rodents and that several therapeutic monoclonal antibodies and antiviral compounds are effective against Omicron BA.2 variants.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Because adult and juvenile eel gobies usually hide within the burrows of muddy substrates, their diversity and life history have not yet been fully elucidated. We investigated larval specimens of the ...eel gobies collected on Okinawa Island in southern Japan. The genus Trypauchenopsis was previously thought to consist of only one species, but our larval collection identified two species, Trypauchenopsis limicola and Trypauchenopsis intermedia, distinguished by their species‐specific melanophore arrangements and differences in their fin‐ray counts. Taenioides kentalleni were previously known from only two specimens worldwide. A third specimen of this species has now been added from the larval collection. In addition to the three species above, Taenioides gracilis and Caragobius urolepis were identified and the larval morphologies of the five species were described for the first time. All the larvae collected in the present study were at late postflexion stage. T. limicola, T. intermedia and T. gracilis were presumably collected in the estuaries and beaches when approaching their adult habitats at the end of pelagic life. They were 8.5–10.3 mm in standard length, and otolith analysis suggests that their pelagic larval durations are a little longer than 1 month (average 34–37 days). The larval occurrence suggested that the spawning season of T. limicola is May–December, when the water temperature is warmer than approximately 20°C. Our work reveals that studying the larval stage can provide new information on the taxonomy and life history of the elusive cryptobenthic fish.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Three bacterial strains, KC07075, KC07079 and KC07084
, were isolated from the oral cavity of cats in 2007 in Japan. These strains were Gram-negative rods, exhibited gliding motility, grew in air ...with 5 % CO
, and showed oxidase activity, but not catalase activity. The 16S rRNA gene sequences of the three strains were 100 % identical. The 16S rRNA gene sequence of strain KC07084
showed 92.1 and 91.9% identity to the type strains of
and
, respectively, and showed 89.3-91.6% identity to other
species. The major cellular fatty acids of strain KC07084
were iso-C
(58.4 %) and summed feature 11 (13.1 %). The G+C content of DNA from strain KC07084
was 33.7 mol%, and the genome size was 2.92 Mbp. Strains KC07075, KC07079 and KC07084
showed digital DNA-DNA hybridization values (dDDH) values of 99.9 % and average nucleotide identity (ANI) values of 99.98 % with each other, strain KC07084
had dDDH values of 18.7-28.2 % and ANI values of 67.12-72.30 % to the type strains of other
species. All known species of the genus
inhabiting the oral cavity of dogs and cats have catalase activity, but the three strains, including type strain KC07084
, lacked catalase activity. These results of the phylogenetic analysis of the 16S rRNA gene sequence, biochemical characteristics, and dDDH and ANI values suggest that strain KC07084
represents a novel species. We propose the name
sp. nov., with KC07084
as the type strain (=JCM 32682
=DSM 107252
).
Antibody titers against SARS-CoV-2 slowly wane over time. Here, we examined how time affects antibody potency. To assess the impact of antibody maturation on durable neutralizing activity against ...original SARS-CoV-2 and emerging variants of concern (VOCs), we analyzed receptor binding domain (RBD)-specific IgG antibodies in convalescent plasma taken 1–10 months after SARS-CoV-2 infection. Longitudinal evaluation of total RBD IgG and neutralizing antibody revealed declining total antibody titers but improved neutralization potency per antibody to original SARS-CoV-2, indicative of antibody response maturation. Neutralization assays with authentic viruses revealed that early antibodies capable of neutralizing original SARS-CoV-2 had limited reactivity toward B.1.351 (501Y.V2) and P.1 (501Y.V3) variants. Antibodies from late convalescents exhibited increased neutralization potency to VOCs, suggesting persistence of cross-neutralizing antibodies in plasma. Thus, maturation of the antibody response to SARS-CoV-2 potentiates cross-neutralizing ability to circulating variants, suggesting that declining antibody titers may not be indicative of declining protection.
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•Qualitative changes in plasma neutralizing antibody are longitudinally analyzed•Affinity-matured antibodies with resistance to variants are durably maintained•Neutralizing potency and breadth to SARS-CoV-2 variants increase with time•Serological immunity evolves with time to counter SARS-CoV-2 variants
Antigenic drifts in SARS-CoV-2 variants permit escape from neutralizing antibody in COVID-19 convalescent plasma. Moriyama et al. reveal the evolution of serological immunity with time that counters SARS-CoV-2 variants via affinity maturation and durable elicitation of IgG antibodies that are resistant to viral escape.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The BA.2 sublineage of the SARS-CoV-2 Omicron variant has become dominant in most countries around the world; however, the prevalence of BA.4 and BA.5 is increasing rapidly in several regions. BA.2 ...is less pathogenic in animal models than previously circulating variants of concern
. Compared with BA.2, however, BA.4 and BA.5 possess additional substitutions in the spike protein, which play a key role in viral entry, raising concerns that the replication capacity and pathogenicity of BA.4 and BA.5 are higher than those of BA.2. Here we have evaluated the replicative ability and pathogenicity of BA.4 and BA.5 isolates in wild-type Syrian hamsters, human ACE2 (hACE2) transgenic hamsters and hACE2 transgenic mice. We have observed no obvious differences among BA.2, BA.4 and BA.5 isolates in growth ability or pathogenicity in rodent models, and less pathogenicity compared to a previously circulating Delta (B.1.617.2 lineage) isolate. In addition, in vivo competition experiments revealed that BA.5 outcompeted BA.2 in hamsters, whereas BA.4 and BA.2 exhibited similar fitness. These findings suggest that BA.4 and BA.5 clinical isolates have similar pathogenicity to BA.2 in rodents and that BA.5 possesses viral fitness superior to that of BA.2.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In cultured cells, SARS-CoV-2 infects cells via multiple pathways using different host proteases. Recent studies have shown that the furin and TMPRSS2 (furin/TMPRSS2)-dependent pathway plays a minor ...role in infection of the Omicron variant. Here, we confirm that Omicron uses the furin/TMPRSS2-dependent pathway inefficiently and enters cells mainly using the cathepsin-dependent endocytosis pathway in TMPRSS2-expressing VeroE6/TMPRSS2 and Calu-3 cells. This is the case despite efficient cleavage of the spike protein of Omicron. However, in the airways of TMPRSS2-knockout mice, Omicron infection is significantly reduced. We furthermore show that propagation of the mouse-adapted SARS-CoV-2 QHmusX strain and human clinical isolates of Beta and Gamma is reduced in TMPRSS2-knockout mice. Therefore, the Omicron variant isn't an exception in using TMPRSS2 in vivo, and analysis with TMPRSS2-knockout mice is important when evaluating SARS-CoV-2 variants. In conclusion, this study shows that TMPRSS2 is critically important for SARS-CoV-2 infection of murine airways, including the Omicron variant.
In vitro assessment of the susceptibility of BA.2.75 to approved antibodies and antivirals showed neutralizing efficacy by bebtelovimab and tixagevimab–cilgavimab. Remdesivir, molnupiravir, and ...nirmatrelvir may also be effective.
Type II feline coronavirus (FCoV) emerged via double recombination between type I FCoV and type II canine coronavirus (CCoV). In this study, two type I FCoVs, three type II FCoVs and ten type II ...CCoVs were genetically compared. The results showed that three Japanese type II FCoVs, M91-267, KUK-H/L and Tokyo/cat/130627, also emerged by homologous recombination between type I FCoV and type II CCoV and their parent viruses were genetically different from one another. In addition, the 3'-terminal recombination sites of M91-267, KUK-H/L and Tokyo/cat/130627 were different from one another within the genes encoding membrane and spike proteins, and the 5'-terminal recombination sites were also located at different regions of ORF1. These results indicate that at least three Japanese type II FCoVs emerged independently. Sera from a cat experimentally infected with type I FCoV was unable to neutralize type II CCoV infection, indicating that cats persistently infected with type I FCoV may be superinfected with type II CCoV. Our previous study reported that few Japanese cats have antibody against type II FCoV. All of these observations suggest that type II FCoV emerged inside the cat body and is unable to readily spread among cats, indicating that these recombination events for emergence of pathogenic coronaviruses occur frequently.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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