̽��ֱ�� of Cambridge - Dami Collier

Pfizer BioNTech vaccine likely to be effective against B1.1.7 strain of SARS-CoV-2

cjb250 — Tue, 02 Feb 2021 12:48:30 +0000

̽��ֱ��preliminary data, which have yet to be to peer-reviewed [see update below] and relate to only a small number of patients, also suggest that a significant proportion of over-eighty olds may not be sufficiently protected against infection until they have received their second dose of the vaccine.

As the SARS-CoV-2 virus replicates and spreads, errors in its genetic code can lead to changes in the virus. Towards the end of 2020, the Cambridge-led COVID-19 Genomics UK (COG-UK) Consortium identified a variant of the virus (now known as B1.1.7) which includes important changes that change the structure of the Spike protein, including the ΔH69/ΔV70 and Δ144/145 amino acid deletions and N501Y, A570D and P681H mutations. Researchers at Cambridge/COG-UK now report seeing a number of virus sequences that also include the E484K mutation, first seen in the South African variant.

̽��ֱ��emergence of the B1.1.7 strain has led to strict lockdown measures in the UK because of concerns over its transmissibility. There is particular concern that these changes might enable the virus to ‘escape’ the newly-developed vaccines, which typically target the Spike protein.

̽��ֱ��UK has begun rolling out two vaccines – the Pfizer BioNTech vaccine and the Oxford AstraZeneca vaccine. ̽��ֱ��efficacy of the vaccines can be boosted by a second dose; however, in order to reach as large a number of people as possible in a short amount of time, the government has concentrated on delivering a first dose to as many individuals as possible by giving the second dose at 12 weeks, rather than three.

Researchers at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), ̽��ֱ�� of Cambridge, working in collaboration with the NIHR Covid-19 BioResource, used blood samples from 26 individuals who had received their first dose of the Pfizer vaccine three weeks previously, to extract serum, which contains antibodies raised in response to the vaccine. ̽��ֱ��age range of the volunteers was 29 to 89 years.

Working under secure conditions, the team created a synthetic version of the SARS-CoV-2 virus, known as a pseudovirus. When they tested the individuals’ sera against this pseudovirus, they found that all but seven of the individuals had levels of antibodies sufficiently high to neutralise the virus – that is, to protect against infection.

When the team added all eight Spike protein mutations found in B1.1.7 to the pseudovirus, they found that the efficacy of the vaccine was affected by the B1.1.7 mutations, which required higher concentrations of antibody in the sera to neutralise the virus. Although there was a wide range of variation between individuals, on average B1.1.7 required around a two-fold increase in the concentration of serum antibody.

However, when the E484K mutation was added, substantially higher levels of antibody were required – on average this mutation required an almost ten-fold increase in the concentration of serum antibody for neutralisation when compared to the strain circulating prior to B.1.1.7.

Professor Ravi Gupta from CITIID, who led the study, said: “Our findings suggest that the Pfizer BioNTech vaccine is likely to offer similar protection against B1.1.7 as it does against the previous strain of SARS-CoV-2. Although we found a reduction in the ability of antibodies to neutralise the virus, given the number of antibodies produced following vaccination, this should still only have a relatively modest effect and people should still be protected.

“Of particular concern, though, is the emergence of the E484K mutation, which so far has only been seen in a relatively small number of individuals. Our work suggests the vaccine is likely to be less effective when dealing with this mutation.

“B1.1.7 will continue to acquire mutations seen in the other variants of concern, so we need to plan for the next generation of vaccines to have modifications to account for new variants. We also need to scale up vaccines as fast and as broadly as possible to get transmission down globally.”

̽��ֱ��seven individuals who were unable to neutralise the virus after the first dose were all aged over 80 years old. This accounts for almost half of the 15 individuals in this age group. However, at a follow-up visit after these individuals had received their second dose (given at three weeks), they were all able to neutralise the virus.

Dr Dami Collier, the main co-investigator on the studies, added: “Our data suggest that a significant proportion of people aged over eighty may not have developed protective neutralising antibodies against infection three weeks after their first dose of the vaccine. But it’s reassuring to see that after two doses, serum from every individual was able to neutralise the virus.”

̽��ֱ��researchers have released their data ahead of peer review because of the urgent need to share information relating to the pandemic, and particularly the new UK variant.

̽��ֱ��research was supported by Wellcome, the Medical Research Council, the Bill and Melinda Gates Foundation and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre.

Reference
SARS-CoV-2 B.1.1.7 escape from mRNA vaccine-elicited neutralizing antibodies

Update: 11 March 2021

̽��ֱ��study has now been peer-reviewed and is published in Nature:

Collier, DA et al. SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited antibodies. Nature; 11 March 2021; DOI: 10.1038/s41586-021-03412-7

̽��ֱ��Pfizer BioNTech vaccine BNT162b2 is likely to be effective against the B1.1.7 variant of SARS-CoV-2, even though its efficacy is modestly affected, say scientists at the ̽��ֱ�� of Cambridge. However, when the E484K mutation – first seen in the South African variant – is added, it substantially increases the amount of antibody required to prevent infection.

B1.1.7 will continue to acquire mutations seen in the other variants of concern, so we need to plan for the next generation of vaccines to have modifications to account for new variants. We also need to scale up vaccines as fast and as broadly as possible to get transmission down globally

Ravi Gupta

MasterTux

Syringe and vaccine

̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Rapid coronavirus test speeds up access to urgent care and will free up beds ahead of winter

fpjl2 — Wed, 03 Jun 2020 10:43:55 +0000

̽��ֱ��first analysis of a new point-of-care 'nucleic acid test' for SARS-CoV-2 in a UK hospital setting shows these machines dramatically reduce time spent on COVID-19 ‘holding’ wards – allowing patients to be treated or discharged far quicker than with current lab testing set-ups.

̽��ֱ��rapid diagnostic capability of SAMBA II devices – an average of 2.6 hours compared with 26.4 hours for standard lab tests – led to an increased availability of ‘isolation rooms’ needed for infected patients, as well as fewer hospital bay closures.

̽��ֱ�� of Cambridge researchers behind the new study, currently a pre-print and awaiting peer-review, say that the time and hospital capacity spared by these devices will be “critical as we move towards autumn and winter”.

̽��ֱ��SAMBA II machine was developed by a ̽��ֱ�� spinout company, Diagnostics in the Real World, and deployed for trials in Addenbrooke’s Hospital, part of Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH).

“ ̽��ֱ��backlog of routine operations and screenings as a result of the pandemic is a huge issue, and must be resolved ahead of winter, when the NHS will face even more pressure from other infections like norovirus and influenza,” said study lead author Professor Ravi Gupta.

“Rapidly testing admissions for SARS-CoV-2 at the point of care is essential for reducing COVID-19 transmission in hospitals, speeding up access to urgent care and allowing safe discharge to care homes. It could make all the difference in a few months’ time.”

“Use of point-of-care testing would speed up the identification of patients for COVID-19 clinical trials, and receiving an experimental treatment a day earlier could make a clinical difference.”

“Hospitals across the UK, as well as care homes and prisons, could benefit from SAMBA II devices,” said Gupta, from the Cambridge Institute of Therapeutic Immunology & Infectious Diseases (CITIID). “Given the technological capital of the UK we should not be falling so short on rapid point-of-care testing.”

Standard tests are sent for analysis in central laboratories, where backlogs can see delays of two days or more. SAMBA machines can produce a diagnosis in as little as 90 minutes.

Dr Helen Lee, CEO of Diagnostics in the Real World, developed the SAMBA II technology while at Cambridge’s Department of Haematology. ̽��ֱ��chemistry behind the machines has been used for on-the-spot HIV diagnostics across Africa.

̽��ֱ��devices search for tiny traces of virus genetic code, and are extremely sensitive in the detection of active infections. Once nose and throat swabs have been loaded into a SAMBA machine, the process is fully automated, making them easy to use.

̽��ֱ��initial ‘COVIDx’ clinical study led by Gupta at Addenbrooke’s with 149 participants found SAMBA II had 96.9% sensitivity (accurate identification of positive cases) and 99.1% specificity (accurate identification of negative cases) compared to the standard lab test. It was also around 24 hours faster.

̽��ֱ��success of the COVIDx study saw the hospital switch nearly all of its SARS-CoV-2 testing from the standard lab ‘RT-PCR’ tests over to the use of SAMBA II during May: an opportunity for a “real-world” comparison and its effect on hospital functioning.

Gupta and colleagues compared data from the electronic patient records of all those who had in-hospital tests done in the ten days before and then after the switch to SAMBA devices at CUH.

̽��ֱ��researchers found that the average length of time patients had to spend on a COVID019 ‘holding’ ward before they could be discharged or progress with treatment almost halved: dropping from 58.5 hours to just 30 hours.

They also saw a fall in use of the single-occupancy ‘isolation’ rooms in which COVID-19 patients are ideally treated – from 30.8% to 21.2% after SAMBA’s introduction, as patients with symptoms were shown to be COVID-19 negative.

In fact, the researchers say the testing devices prevented 11 ward closures in the ten days after implementation. “Keeping surgical bays open means fewer cancelled operations, speeding up access to life-saving clinical intervention,” said Gupta.

̽��ֱ��majority of those tested using SAMBA II during the first ten days of hospital-wide use were admissions to the Emergency Department (ED). ̽��ֱ��remainder included pre-op screenings and discharges to nursing homes.

̽��ֱ��SAMBA II tests were “beneficial” for 76% of ED patients: expediting treatment or discharge, and allowing the release of examination rooms. ̽��ֱ��24% without benefit was mainly due to triage or discharge before results were returned.

Some 96% of the SAMBA testing on pre-operative patients increased speed of “surgical intervention”, including kidney and liver transplants. ̽��ֱ��tests also allowed earlier discharge to nursing homes or into supported living in 79% of those cases, with the remainder delayed by “systematic issues” not tests themselves.

Dr Dami Collier, who coordinated and analysed COVIDx, said: “Our research demonstrates that point-of-care testing with SAMBA II machines is not only reliable, accurate and much faster, but that the diagnostic speed leads to significant real-world improvements for patient care and safety.”

CUH Medical Director, Dr Ashley Shaw, said: “Point of care testing has been hugely beneficial in enabling our clinical teams to make well-informed and timely decisions, keeping patients and staff as safe as possible throughout this difficult period.”

This work was supported by Wellcome, the Addenbrooke’s Charitable Trust, and the National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre.

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Researchers say faster tests helped expedite access to life-saving treatments such as organ transplants – and might make all the difference later this year.

Rapidly testing admissions for SARS-CoV-2 at the point of care is essential for reducing COVID-19 transmission in hospitals, speeding up access to urgent care and allowing safe discharge to care homes

Ravi Gupta

Cambridge ̽��ֱ�� Hospitals

Research nurse from the NIHR Clinical Research Facility processing patient samples using SAMBA machines at Adden brooke’s Hospital in Cambridge

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