Delta 4+ variant: Complete vaccine escape & enhanced infectivity with Pfizer vaccine

“Here we suggest an evolutionary pathway by which the Delta variant could achieve complete escape from vaccine-induced immunity”.   Although Pfizer-BioNTech BNT162b2-immune sera neutralized the Delta variant, when four common mutations were introduced into the receptor binding domain (RBD) of the Delta variant (Delta 4+), some BNT162b2-immune sera lost neutralizing activity and enhanced the infectivity.

Unique mutations in the Delta NTD were involved in the enhanced infectivity by the BNT162b2-immune sera. Sera of mice immunized by Delta spike, but not wild-type spike, consistently neutralized the Delta 4+ variant without enhancing infectivity.

The 4 key mutations inserted were K417N, N439K, E484K and N501Y.

 

Preprint: The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines 

 

 

Public Health England releases detailed vaccine breakthrough information

 

So what is Plan B if the vaccines fail?

 

 

India: Delta Plus Delta-AY.1 dominant in Tripura – found in 138 out of 151 coronavirus sequences

At least 138 of the 151 Covid-19 samples sent by Tripura for genome sequencing have tested positive for the Delta Plus variant, State Health Surveillance Officer Dr Deep Kumar Debbarma said. Tripura, thus, is the first state in the northeast to have recorded a case of the Delta Plus variant.

Addressing reporters on Friday evening, Debbarma said the samples were sent to a laboratory at Kalyani, West Bengal, for the virological test. “Delta Plus variant was found in 138 of the 151 samples. 10 others tested positive for the Delta variant while three cases of alpha variant were found,” Debbarma added.

Indian Express Report

Poland: 106 cases of Delta and 12 cases of Delta Plus aka Delta-AY.1 coronavirus variant

Poland has confirmed 106 cases of the Delta and 12 cases of the Delta Plus (Delta-AY.1 or Delta with K417N mutation) coronavirus variants that originated in India, a deputy health minister has announced.

Speaking to Polish public Radio One on Friday, Waldemar Kraska presented a report on the new variants.

“I have just received a report showing that currently we have 106 confirmed Delta cases. We also have 12 confirmed cases of Delta Plus,” Kraska said.

TheFirstNews.com report

 

USA/UK: 2 separate clades of Delta #coronavirus variant with K417N – AY.1 and AY.2

 

 

 

Image by Dimitris Vetsikas from Pixabay

USA/UK: 2 separate clades of Delta #coronavirus variant with K417N – AY.1 and AY.2

Through routine scanning of variation in Delta, a small number of sequences were detected which had acquired the spike protein mutation K417N. Information suggests that there are at least 2 separate clades of Delta with K417N. One clade is large and internationally distributed with PANGO lineage designation AY.1.  A second clade found in sequences uploaded to GISAID from the USA, now designated AY.2.

As of 16 June 2021, 161 genomes of Delta-AY.1 have been identified on GISAID. from Canada (1), India (8), Japan (15), Nepal (3), Poland (9), Portugal (22), Russia (1), Switzerland (18), Turkey (1), USA (83).

There are currently 38 cases of Delta-AY.1 in England (36 confirmed sequencing and 2 probable genotyping). Cases have been detected in 6 different regions in England. Delta-AY.2 has not been detected in England.

UK Variants of Concern Technical Briefing 15 (PDF download)

 

According to Bani Jolly of the Institute of Genomics and Integrative Biology, the phylogeny of Delta has two separate clades. While AY.1 is found in a few countries including the UK, India and Nepal, the other clade (AY.2), is largely from the sequences from California (USA).

“The split between the two clades seems to be based on two spike mutations — A222V and T95I. While all sequences in the California cluster share spike A222V, all sequences in the larger international cluster share spike T95I,” Jolly tweeted.

Stating that AY.1 has arisen independently a number of times and could be more prevalent than observed in countries with limited genomic surveillance, she tweeted that given that Delta is a variant of concern, it is important to take note of any sub-lineages that may emerge.

Time of India report

 

 

 

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Nepal: nearly 20% of Delta #coronavirus sequences have K417N mutation – mountaineers variant increasing

The Nepalese Ministry of Health and Population (MoHP) said that out of 47 confirmed delta variant samples, nine were found to have K417N mutations.

According to the ministry, the new mutation has also been named AY.1 (aka Delta-AY.1 or “Mountaineers” variant).

Issuing a press statement on Monday, the MoHP revealed that AY.1 mutation has been confirmed in more than 10 countries, including Nepal.

With this, Nepal has witnessed Alpha and Delta as the variant of concern and Kappa variant of concern, the Ministry said.

The Ministry had selected 48 samples from the National Public Health Laboratory from the people of all age groups from April 29  to June 3 and tested them in WHO identified Center for Excellence in Genomics, The Institute of Genomics and Integrative Biology (IGIB).

Out of them 47 samples had come with delta variant B.1.617.2 and one had come with alpha variant B.1.1.7. Among the 47 delta variant samples nine had shown K417N mutation, the Ministry said.

Kharbarhub.com report

 

UK: Delta with K417N – the “mountaineers” variant – PHE #coronavirus Delta-AY.1 update

 

UK: “Everest climbers could have spread potentially more infectious and vaccine resistant’ variant

UK: Delta with K417N – the “mountaineers” variant – PHE #coronavirus Delta-AY.1 update

Of the 36 cases of Delta-AY.1 (mountaineers) variant, 27 cases were known to have a vaccination status within the National Immunisation Management System (NIMS). 

“Through routine scanning of variation in Delta a small number of sequences were detected which had acquired the spike protein mutation K417N. Information suggests that there are at least 2 separate clades of Delta with K417N. One clade is large and internationally distributed with PANGO lineage designation AY.1. A second clade found in sequences uploaded to GISAID from the USA. There is limited epidemiological information available at present.

International Epidemiology
As of 7 June 2021, 63 genomes of Delta with K417N have been identified on GISAID. from Canada (1) Germany (1), Russia (1), Nepal (2), Switzerland (4), India (6), Poland (9), Portugal (12), Japan (13), USA (14).

Epidemiology
There are currently 36 cases of Delta-AY.1 in England (35 confirmed sequencing and 1 probable genotyping) plus an additional 10 sequences which include some cases in other UK nations and some genomes for which case data is being sought. The first 5 cases were sequenced on 26 April 2021 and were contacts of travellers to Nepal and Turkey. All these cases were detected in the West Midlands. Cases have been detected in 6 different regions in England (Table 21, Figure 26). The majority of cases are in younger individuals, with 2 cases of age 60 or over (Figure 27). Out of the 36 cases, there were 11 travel associated cases (6 travellers and 5 cases amongst contacts of travellers). Twelve cases have no history of travel or contact with travellers. Countries of travel included red-list countries (Nepal and Turkey), amber-list countries (Malaysia) and green-list countries (Singapore).

Of the 36 cases, 27 cases were known to have a vaccination status within the National Immunisation Management System (NIMS), when linked on NHS number. Of these, 18 cases occurred in people who were not vaccinated, 2 cases in people who had received their first dose within 21 days of specimen date, 5 cases in people who had received their  first dose more than 21 days after specimen date. There was a total of 2 cases where there were more than 14 days between the second dose of vaccine and a positive specimen. No deaths have been recorded amongst the 36 cases.”

PHE download – SARS-CoV-2 variants of concern and variants under investigation in England  – Technical briefing 15 (PDF)

 

UK: The “mountaineers variant” – B.1.617.2 with K417N mutation

 

UK: “Everest climbers could have spread potentially more infectious and vaccine resistant’ variant

 

 

Image by Simon from Pixabay

UK: The “mountaineers variant” – B.1.617.2 with K417N mutation

The Delta variant with the K417N mutation, also known as the “Mountaineers” variant, has cropped up 14 times in Japan, and 13 of those samples were in travellers from Nepal – mostly climbers from Everest expeditions. At least 100 cases were reported at the Everest base camp, it is believed that the variant could have been spread by climbers ascending the mountain despite widespread national lockdowns across the globe.  Cases have also been identified in India, Japan, Portugal, and the UK.

According to Dr Jeff Barrett, director of the COVID-19 Genomics Initiative at the Wellcome Sanger Institute in the UK, at least one case has been found in the US.

DNAIndia.com report: Delta+K417N variant that affected at least 100 Everest climbers

 

The mountaineers variant B.1.617.2 + K417N has also been blamed for the axing of Portugal from the UK’s green travel list. See this report

 

UK: Delta with K417N – the “mountaineers” variant – PHE #coronavirus Delta-AY.1 update

 

UK: “Everest climbers could have spread potentially more infectious and vaccine resistant’ variant

 

Photo by Claire Nolan on Unsplash

India: 16% vaccine breakthrough in Delhi hospital #coronavirus study

A small-scale study on 113 healthcare workers who had received at least one vaccine dose at a private hospital in Delhi found that 18 tested positive for Covid but all except one had mild symptoms.  Of the 113 in the study, 107 had received the second dose of the vaccine.

Taken in percentage form, the study found that breakthrough infections — Covid infection in vaccinated individuals — occurred in 15.9 per cent (18 persons) of the vaccinated individuals and 95 per cent had mild symptoms. Of these, 17 incurred the infection after the second dose. According to the study, of the breakthrough infections in 18 persons, 17 incurred the infection after the second dose. These 17 had got their second dose after a mean of 34.8 days following the first jab.

NDTV report

Seychelles: 30% #coronavirus vaccine breakthrough rate

Seychelles: 30% #coronavirus vaccine breakthrough rate

Image by shalender kumar from Pixabay

Finland: #coronavirus variant resembling B.1.351 (South Africa) found in the Turku infection cluster

The virus variant of South Africa has been confirmed as the cause of the coronavirus infections among students in Turku, Finland. However, the transformation observed at Turku University Central Hospital (Tyks) is not identical to the original South African variant, but seems to have transformed further, says the Hospital District of Southwest Finland.

The matter was clarified in laboratory tests performed in Tyks.

“We found that it is probably a modified virus, and the so-called gene sequencing ensured that the virus has several other changes in addition to those characteristic of the South African variant. So far, we don’t know where the variant came from. These will become clear later when the entire genome of the virus is known” says chief physician of molecular microbiology and virology, Tytti Vuorinen, in a press release.

According to Vuorinen, this is possibly a new type of coronavirus variant. This will be confirmed later in so-called whole genome sequencing.

So far, there is no information on whether a similar modified variant has been found in other countries.

So far, it has not been shown that the modified South African coronavirus variant is more severe than usual. The symptoms of those infected have been fairly mild and the patients have not needed hospital treatment, the release says.

According to the hospital district, the finding does not justify changing the current recommendations.

More than 90 infections have been detected in the Turku cluster.

YLE.fi report

 

Image by Jarkko Mänty from Pixabay

Outbreak of South African #coronavirus variant B.1.351 in Uppsala, Sweden

By March 15, 18 cases had been identified by mutation screening, but the region feared the number was just the tip of the iceberg.

Since then, the outbreak has grown, and the number of infected students is now 47. At the same time, about 15 cases of the variant have also been discovered outside the university, according to Mats Martinell.

“In total, there are about 60 cases in Uppsala. So it is not just students, but we have a social spread.”

DN.se report

 

Image by David Mark from Pixabay

Efficacy of the AstraZeneca #coronavirus vaccine against the B.1.351 South African Variant

Study conclusions:  A two-dose regimen of the ChAdOx1 nCoV-19 [AstraZeneca] vaccine did not show protection against mild-to-moderate Covid-19 due to the B.1.351 [South Africa ] variant.

“Between June 24 and November 9, 2020, we enrolled 2026 HIV-negative adults (median age, 30 years); 1010 and 1011 participants received at least one dose of placebo or vaccine, respectively. Both the pseudovirus and the live-virus neutralization assays showed greater resistance to the B.1.351 variant in serum samples obtained from vaccine recipients than in samples from placebo recipients. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], −49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (92.9%) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, −76.8 to 54.8). The incidence of serious adverse events was balanced between the vaccine and placebo groups.”

Full paper on NEJM

 

Image by MasterTux from Pixabay

South African #coronavirus variant B.1.351 (501Y.V2) at around 15% in Saarland, Germany

German Federal Health Jens Spahn Minister of has expressed concern about the spread of the South African corona variant in Saarland . “It is on the way to 15 percent South Africa variant,” said Spahn in Berlin. “That is by far the highest proportion in all of Germany.”

The variant, which was first discovered in South Africa in August 2020, was increasingly displacing the other variants there. Similar to the British one, this variant also spreads much faster because it can bind to human cells more quickly. But it is also suspected of being able to better escape human immune responses.

Spiegel.de report

 

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Lancet: Surveillance of #coronavirus in Zimbabwe shows dominance of variants of concern – B.1.351 (501Y.V2) and A.23.1

In December, 2020, 95 (89%) of 107 sequenced cases contained mutations of concern, rising to 102 (98%) of 104 in January, 2021. The identified variants included the previously reported B.1.351 (501Y.V2) and A.23.1 variants, along with a novel variant under investigation.

Prospective surveillance of SARS-CoV-2 by genome sequencing in Zimbabwe between December, 2020, and January, 2021 (the period of the so-called second wave), has identified that variants with concerning mutations are prevalent in sequenced samples. In December, 2020, 95 (89%) of 107 sequenced cases contained mutations of concern, rising to 102 (98%) of 104 in January, 2021. The identified variants included the previously reported B.1.351 (501Y.V2) and A.23.1 variants, along with a novel variant under investigation.

The B.1.1.7, B.1.525, P.1, and P.2 and variants were not identified in Zimbabwe. Variants with concerning mutations have all replaced previously identified lineages in Zimbabwe

Lancet report

 

Image by Simon Berger from Pixabay

Antibody resistance of #coronavirus variants B.1.351 (SA) and B.1.1.7 (UK)

“Findings on B.1.351 [South Africa variant] are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple individual mAbs to the receptor-binding motif on RBD, largely owing to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (9.4 fold) and vaccinee sera (10.3-12.4 fold). B.1.351 and emergent variants13,14 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.

Full Paper on Nature Magazine

 

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