Impact of mAb-induced A475V substitution on viral fitness and antibody neutralization of SARS-CoV-2 omicron variants in the presence of monoclonal antibodies and human convalescent sera

Viriyakitkosol, Ratchanont; Wanitchang, Asawin; Srisutthisamphan, Kanjana; Saenboonreung, Janya; Boonkrai, Chatikorn; Pisitkun, Trairak; Jongkaewwattana, Anan

doi:10.3389/fimmu.2023.1219546

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…A475V, in the spike protein substantially reduced the neutralizing activities of monoclonal antibodies and convalescent sera 39 .…”

Section: County Of Losmentioning

confidence: 94%

What We Know about HV.1 (EG.5.1.6.1) SARS-CoV-2 Variant

Cobar,

Cobar

2024

MRAJ

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Background: HV.1 (EG.5.1.6.1) was the dominant strain in the U.S. as of the end of second week of December 2023, according to the U.S. Centers for Disease Control and Prevention (CDC). The strain is a descendant of EG.5 family that was identified in China in February 2023 and was first detected in the United States in April 2023. 44 mutations in S-protein, 2 in Membrane and Envelope viral structures, 5 mutations in the Nucleocapsid, 21 mutations in Orf1a, 1 mutation in Orf3a, Orf6, Orf10, and 2 mutations in Orf8 virus genome open reading frames are reported. The symptoms of HV.1 are similar that of other Omicron variants, these include fever or chills, cough, shortness of breath or difficulty breathing, fatigue, muscle or body aches, headache, new loss of taste or smell, sore throat, congestion or runny nose, nausea or vomiting, and diarrhea, but congestion, sore throat and dry cough seem to be the three most prominent symptoms right now. Since HV.1 belongs to the same family as XBB, health experts assumethat updated vaccines are expected to be effective against this new dominant subvariant.The only way to distinguish (COVID-19) from RSV and flu, both of which are now gaining steam, is by testing. Aim: The purpose of the manuscript is to present a systematic review on the prevalence, structural, genomic, and pathogenic characteristics of HV.1 from October 1, 2023, as of December 31, 2023, emphasizing on the variant genetic characteristics, contagiousness, and potential pathogenicity. Material and Methods: Original scientific articles published in Medline, Pubmed, Science Direct, Web of Science, Scopus, EBSCO and BioMed Central databases, official health organizations electronic publications, and specialized media in the subject, were electronically searched to accomplish the aim of the study. Articles published in any language were included from October 2023 to present using a variety of keywords in combination. The studies relevant to our review were analysed and compared. Results and Discussion: HV.1 showed significantly lower plasma neutralisation titers compared with their parental strains after acquiring L452R and A475V mutations, explaining their growth advantages. A475V mutation also resulted in decreased binding affinity, enhancing immune evasion compared to HK.3 (XBB.1.5+FLip). However, the L452R mutation of HV.1 did not affect binding affinity. 44 mutations in S-protein, 2 in Membrane and Envelope viral structures, 5 in the Nucleocapsid, 21 in Orf1a, 1 mutation in Orf3a, Orf6, Orf10, and 2 in Orf8 virus genome open reading frames mutations are reported. These mutations give to HV.1 improved ability to enter the human cell, although no greater pathogenicity or severity of the symptoms. Conclusions: The latest data from US-CDC in 2023, shows HV.1 as the second prevalent SARS-CoV-2 variant in the United States. HV.1 (XBB.1.9.2.5.1.6.1 or EG.5.1.6.1) in October 2023, quickly increase its prevalence and surpassed other variants, includingEG.5 (Eris) to become the most prevalent strain in USA until week ending on December 9, 2023. HV.1 has a similar transmission rate, exhibits a greater evasive capacity of immune-generated antibodies than EG.5.1* family of SARS-CoV-2, produce similar symptoms that of other Omicron variants, are expected not to produce an increase in hospitalizations and mortality rate and the SARS-CoV-2 vaccines recently developed by Pfizer and Moderna, must be effective against this Omicron subvariant.For now HV.1 does not seem harmful in terms of creating a deadly disease but is still contagious enough to not be ignored.

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“…A475V, in the spike protein substantially reduced the neutralizing activities of monoclonal antibodies and convalescent sera 39 .…”

Section: County Of Losmentioning

confidence: 94%

What We Know about HV.1 (EG.5.1.6.1) SARS-CoV-2 Variant

Cobar,

Cobar

2024

MRAJ

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“…As SARS-CoV-2 variants spreads amid growing population immunity, its tendency for antibody escape has become a key determinant of variant fitness [ 30 ]. This enables Omicron to readily infect those vaccinated or previously infected, and undergo adaptive evolution under selection pressures imposed by antibodies and therapeutics [ 31 ]. Therefore, in the background of herd immunity, Omicron exhibits better immune evasion, it is necessary to dynamically detect the prevalence of SARS-CoV-2 variants.…”

Section: Introductionmentioning

confidence: 99%

A regional genomic surveillance program is implemented to monitor the occurrence and emergence of SARS-CoV-2 variants in Yubei District, China

Liu,

Deng,

et al. 2024

Virol J

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Background In December 2022, Chongqing experienced a significant surge in coronavirus disease 2019 (COVID-19) epidemic after adjusting control measures in China. Given the widespread immunization of the population with the BA.5 variant, it is crucial to actively monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant evolution in Chongqing's Yubei district. Methods In this retrospective study based on whole genome sequencing, we collected oropharyngeal and nasal swab of native COVID-19 cases from Yubei district between January to May 2023, along with imported cases from January 2022 to January 2023. Through second-generation sequencing, we generated a total of 578 genomes. Results Phylogenetic analyses revealed these genomes belong to 47 SARS-CoV-2 Pango lineages. BA.5.2.48 was dominant from January to April 2023, rapidly replaced by XBB* variants from April to May 2023. Bayesian Skyline Plot reconstructions indicated a higher evolutionary rate (6.973 × 10–4 subs/site/year) for the XBB.1.5* lineage compared to others. The mean time to the most recent common ancestor (tMRCA) of BA.5.2.48* closely matched BA.2.75* (May 27, 2022). Using multinomial logistic regression, we estimated growth advantages, with XBB.1.9.1 showing the highest growth advantage (1.2, 95% HPI:1.1–1.2), followed by lineage FR.1 (1.1, 95% HPI:1.1–1.2). Conclusions Our monitoring reveals the rapid replacement of the previously prevalent BA.5.2.48 variant by XBB and its sub-variants, underscoring the ineffectiveness of herd immunity and breakthrough BA.5 infections against XBB variants. Given the ongoing evolutionary pressure, sustaining a SARS-CoV-2 genomic surveillance program is imperative.

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“…26 Current studies indicate that the asparagine residue (N) 32 of the 1D1 Fab forms a hydrogen bond with A475 of the SARS-CoV-2 RBD. 27 Therefore, substituting alanine with valine at this position could disrupt the interaction and reduce the binding of mAb 1D1 to the BA.5 spike. It was also discovered that despite the disruption of the hydrogen bond between A475 and N32 by the A475V mutation, 1D1 retains its neutralizing ability against the BA.2 spike.…”

Section: Introductionmentioning

confidence: 99%