Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka

Ranasinghe, D.M.S.H.K.; Jayathilaka, Deshni; Jeewandara, Chandima; Gunasinghe, Dumni; Ariyaratne, Dinuka; Jayadasa, Tibutius; Kuruppu, Heshan; Wijesinghe, Ayesha; Bary, Farah; Madushanka, Deshan; Pushpakumara, Pradeep Darshana; Guruge, Dinuka; Wijayamuni, Ruwan; Ogg, Graham; Malavige, Gathsaurie Neelika

doi:10.1101/2022.02.05.22270436

Cited by 3 publications

(9 citation statements)

References 16 publications

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“…We previously showed that by end of January 2021, the overall seroprevalence rates of this population was 24.5% [18]. The number of cases markedly increased from mid-April to June due to the alpha variant [19], while the outbreak due to the delta variant was predominantly from mid-July 2021 to November 2021 [24]. Therefore, these PLOS GLOBAL PUBLIC HEALTH individuals were recruited to the study, while the cases due to the delta variant was starting rise.…”

Section: Discussionmentioning

confidence: 91%

Antibody responses to Sinopharm/BBIBP-CorV in pregnant mothers in Sri Lanka

Jeewandara

Jayampathi

Ranasinghe

et al. 2022

PLOS Glob Public Health

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Background There are limited data regarding the safety and immunogenicity of the Sinopharm/BBIBP-CorV vaccine in pregnancy. Therefore, we sought to investigate the antibody responses and maternal and fetal adverse events following this vaccine in pregnant mothers in Sri Lanka. Methods and findings SARS-CoV-2 receptor binding domain (RBD) specific total antibodies and ACE2 blocking antibodies were measured by ELISA in pregnant mothers (n = 94) who received the vaccine in the first (n = 2), second (n = 57) and third (n = 33) trimester of pregnancy. Data regarding adverse events and fetal and maternal outcomes were obtained from the women once they delivered. No adverse maternal or fetal complications reported such as miscarriage, thrombotic events, hypertensive disorders, fetal death, preterm delivery, or congenital anomalies were reported. 58/94 (61.7%) had RBD binding antibodies and were found to be seropositive at the time of recruitment. All women seroconverted after the second dose and 31/36 previously uninfected women and 57/58 previously infected women gave a positive response to ACE2 blocking antibodies. The RBD binding antibody levels (p = 0.0002) and ACE2 blocking antibodies (p<0.0001) were significantly higher in previously infected individuals post-second dose compared to uninfected individuals. Conclusions The Sinopharm/ BBIBP-CorV vaccine appeared safe and induced high seroconversion rates and ACE2 blocking antibodies in pregnant mothers in the second and third trimester in pregnancy. However, the RBD binding antibodies and ACE2 blocking antibodies post-second dose were significantly higher in previously infected pregnant mothers post-second dose, suggesting that two doses of the vaccine are likely to be less immunogenic in previously unexposed individuals.

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Section: Discussionmentioning

confidence: 91%

Antibody responses to Sinopharm/BBIBP-CorV in pregnant mothers in Sri Lanka

Jeewandara

Jayampathi

Ranasinghe

et al. 2022

PLOS Glob Public Health

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“…Structural biology performed in this study attributes this advantage to the A701S mutation. At the pinnacle of the delta variant (August to September 2021), AY.28 sublineage was responsible for 128/189 (67.7%) of the infections, showcasing again the heightened virulence of the strain in concern [12]. As for disease severity, AY.28 sublineage is sublethal with only 3/160 developing midsevere illness with one individual succumbing to the strain, while there were no deaths in the derived sibling (AY.104) and parental (B.1.617.2) strains [12].…”

Section: Molecular Epidemiology Molecular Epidemiology Of the Delta V...mentioning

confidence: 99%

“…Lanka can be inferred by sequencing of SARS-CoV-2 genomes. ree mutations, A222V (92.80%), A701S (88.06%), and A1078S (92.04%), were classified as lineage specific mutations in the AY.28 sublineage [12]. e authors of the abovementioned preprint suggests a fitness superiority of the AY.28 sublineage of the delta variant, over the co-occurring strains, which are identified as B.1.617.2 (parental) and AY.104 (sibling strain).…”

Section: Molecular Epidemiology Molecular Epidemiology Of the Delta V...mentioning

confidence: 99%

“…e authors of the abovementioned preprint suggests a fitness superiority of the AY.28 sublineage of the delta variant, over the co-occurring strains, which are identified as B.1.617.2 (parental) and AY.104 (sibling strain). Here, the fitness advantage of AY.28 is attributed to the A222V mutation, which is the second most prevalent substitution in the spike protein and is known to be benign on the virus phenotype [12]. e elevated presence of the A222V mutation is attributed to luck than to a selective advantage.…”

Section: Molecular Epidemiology Molecular Epidemiology Of the Delta V...mentioning

confidence: 99%

“…From the Colombo district (Sri Lanka) itself during the time period of July 2021 to October 2021, AY.28 was responsible for 57% of the delta genomes sequenced, while the other two strains, derived (AY.104) and parental (B.1.617.2), were found at 24.8% and 8% occurrence frequencies [12]. erefore, molecular epidemiology suggests that one, two, or all three of the mutations, A222V, A701S, and A1078S, as providing a fitness advantage (in transmission) above the parental strain, B.1.617.2.…”

Section: Molecular Epidemiology Molecular Epidemiology Of the Delta V...mentioning

confidence: 99%

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Genetic, Structural, Physicochemical, and Molecular Epidemiological Landscape of Three New Mutations Found in the Spike (S) Protein of Highly Transmissible Sri Lankan Delta Variant Sub‐lineage AY.28: A222V, A701S, and A1078S

Gunawardana

2022

Journal of Environmental and Public Health

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Recently, three new mutations were identified in Sri Lanka in the spike protein of the rapidly spreading delta variant of the SARS-CoV-2 virus identified by the sublineage AY.28. They were A222V, A701S, and A1078S. The primary focus here is on the A701S mutation that is (1) found in the immediate vicinity of the S1/S2 cleavage site (PRRAR ∗ SV) that separates S1 and S2 subunits of the spike protein; (2) has high structural disorder of the region spanning Serine-701 (Ser-701), which promotes a longer flexible loop forming a better substrate; (3) collapses a loose, short, unstable, tripeptide beta strand (ENS), which is likely to assist the host proteases to cleave the S1-S2 interface easily than when an alanine is present. The same A701S mutation is found in at least 10 other strains of SARS-CoV-2 found in India, USA (East and West Coasts), and China, which classifies this mutation as geographically widespread and convergent in etiology. Conversely, the A1078S mutation is a highly present (>60 strains) mutation in terms of the SARS-CoV-2 coronaviruses, while the highly abundant A222V mutation is inferred by the genetic code, structural and topological features, and placement (in a beta strand) to be an innocuous, conservative mutation. The critical nature of S1/S2-dependent cleavage of S1 and S2 subunits of the spike protein makes the A701S mutation one of significance not just for possible higher virus transmission but also for subsequent fates such as viral load and vaccine effectivity against the delta variant.

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Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals

Pushpakumara

Jeewandara

Bary

et al. 2023

Preprint

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Background: As there are limited data on B cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. Methods: Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n=30), WT infected (n=30), delta infected (n=30), omicron infected+vaccinated (n=20) and Sinopharm (BBIBP-CorV) vaccinees (n=30). We then investigated the sensitivity and specificity of these immunodominant regions and analysed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses and bat Sarbecoviruses. We then investigated the kinetics of responses to these regions in those with varying severity of acute COVID-19. Results: We identified four immunodominant regions aa 29-52, aa 155-178, aa 274 to 297 and aa 365 to 388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, with WT infected individuals predominantly recognizing aa155 to 178 regions, delta infected individuals and vaccinated+omicron infected individuals predominantly recognizing regions aa 29 to 52 and aa 274 to 294 regions. Sinopharm vaccinees recognized all four regions, with the magnitude of responses significantly lower than other groups. >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. Conclusions: N-protein specific responses appear to be detectable in over 90% of those who were naturally infected or vaccinated with a whole virus inactivated vaccine, with responses mainly directed against four regions of the protein, which were highly conserved. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines.

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Molecular epidemiology of AY.28 and AY.104 delta sub-lineages in Sri Lanka

Cited by 3 publications

References 16 publications

Antibody responses to Sinopharm/BBIBP-CorV in pregnant mothers in Sri Lanka

Antibody responses to Sinopharm/BBIBP-CorV in pregnant mothers in Sri Lanka

Genetic, Structural, Physicochemical, and Molecular Epidemiological Landscape of Three New Mutations Found in the Spike (S) Protein of Highly Transmissible Sri Lankan Delta Variant Sub‐lineage AY.28: A222V, A701S, and A1078S

Identification of differences in the magnitude and specificity of SARS-CoV-2 nucleocapsid antibody responses in naturally infected and vaccinated individuals

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