̽��ֱ�� of Cambridge - Ravindra Gupta

Prioritise vaccine boosters for vulnerable immunocompromised patients, say scientists

cjb250 — Wed, 12 Feb 2025 19:00:46 +0000

̽��ֱ��findings, published today in Science Advances, suggest that such individuals will need regular vaccine boosters to protect them and reduce the risk of infections that could be severe and also lead to new ‘variants of concern’ emerging.

Almost 16 million people worldwide are estimated to have died from Covid-19 during 2020 and 2021, though nearly 20 million deaths are thought to have been prevented as a result of the rapid rollout of vaccines against SARS-CoV-2, the virus that caused the pandemic.

During the pandemic, researchers discovered that immunocompromised individuals had difficulty clearing the virus, even when vaccinated. These are people whose immune systems are not functioning correctly, either as a direct result of disease or because they are on medication to dampen down their immune systems, for example to prevent organ transplant rejection. This meant that their infections lasted longer, giving the virus more opportunities to mutate.

Research from early in the pandemic showed that chronic infections can give rise to variants of concern that can then cause new waves of infection in the wider population.

When an individual is vaccinated, their immune systems produce antibodies that recognise and launch an attack on the virus. Such a process is known as seroconversion. Additional ‘booster’ vaccinations increase seroconversion and hence the likelihood of clearing infection.

However, although most immunocompromised individuals will have received three or more doses of the Covid-19 vaccine, they still account for more than a fifth of hospitalisations, admissions to intensive care units, and overall deaths associated with the disease.

To see why this is the case, scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) at the ̽��ֱ�� of Cambridge examined immunocompromised individuals who had been vaccinated against Covid-19. These patients, recruited from Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, were living with vasculitis, a group of disorders that cause inflammation of blood vessels. Data from this group was compared against individuals who were not immunocompromised.

Treatments for vasculitis rely on immunosuppressant medicines. These include drugs such as rituximab, which depletes the number of B-cells in the body – but B-cells are the immune cells responsible for producing antibodies. As such, these individuals are a severely at-risk population.

When the researchers analysed bloods samples from the vasculitis patients, they found that even though vaccination induced seroconversion, this in itself was not always sufficient to neutralise the virus. Every immunocompromised individual required at least three doses of the vaccine to protect them across a range of variants up to and include Omicron (the variant that appeared towards the end of 2021 and caused a new wave of infections). In some cases, even four vaccinations were not sufficient to adequately protect them.

Kimia Kamelian, a Gates Cambridge Scholar at CITIID and St Edmund's College, Cambridge, said: “We know that immunocompromised individuals are particularly vulnerable to diseases such as Covid-19 because their immune systems struggle to clear infections. Vaccinations offer some protection, but our study shows that only repeated vaccinations – often four or more – offer the necessary protection.”

Professor Ravi Gupta, also from CITIID and a Fellow at Homerton College, Cambridge, added: “This of course has implications for the individual, who is more likely to have prolonged infection and a much greater risk of severe infection, but it also gives the virus multiple opportunities to mutate.

“We know from our previous work that at least some of the variants of concern probably emerged during chronic infections. That’s why these individuals must be given priority for updated vaccines against new variants.”

̽��ֱ��research was funded by Wellcome, Gates Cambridge, Addenbrooke’s Charitable Trust and Vasculitis UK, with additional support by the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference
Kamelian, K et al. Humoral responses to SARS-CoV-2 vaccine in vasculitis-related immune suppression. Sci Adv; 12 Feb 2025; DOI: 10.1126/sciadv.adq3342

Vaccinations alone may not be enough to protect people with compromised immune systems from infection, even if the vaccine has generated the production of antibodies, new research from the ̽��ֱ�� of Cambridge has shown.

We know that immunocompromised individuals are particularly vulnerable to diseases such as Covid-19 because their immune systems struggle to clear infections

Kimia Kamelian

NoSystem images

Vaccination of an senior male

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 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 – 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.

Yes

Cambridge start-up wins funding to develop new diagnostics

skbf2 — Mon, 20 Mar 2023 14:25:48 +0000

̽��ֱ��first Innovate UK award, received in 2021, allowed SMi to partner with the Cambridge Institute of Therapeutic Immunology and Infectious Disease, the Medicines Discovery Catapult and the National Physical Laboratory to develop its technology for testing for respiratory diseases. ̽��ֱ��second award, made in early 2023, is helping SMi and its partners apply the same technology to detecting cancer.

Co-founded in 2018 by former ̽��ֱ�� of Cambridge researcher Dr Andrew Thompson, SMi is developing a new technology that analyses samples using super-resolution imaging. ̽��ֱ��technology can detect, quantify and characterise single molecules that are of interest, including DNA, RNA and protein molecules associated with specific diseases. It can visualise what other technologies cannot see and very rapidly batch analyse hundreds of samples with extremely high accuracy.

̽��ֱ��first round of £1.9m funding enabled SMi to develop its platform, used for the simultaneous screening of common respiratory diseases. ̽��ֱ��COVID-19 pandemic demonstrated the need for rapid and cost-effective diagnostic testing on a massive scale. Test accuracy and the ability to identify new variants were critical.

̽��ֱ��second Innovate UK award has funded the application of SMi’s platform to cancer diagnosis by enabling work with another team of specialists at the Medicines Discovery Catapult. Here the same single molecule visualisation approach is being used to detect and quantify cancer biomarkers in patient blood samples. This will help clinicians to make more accurate assessments, and combined with the flexibility, accuracy, speed and high throughput of SMi’s technology, could reduce diagnostic backlogs and provide patients with their results much sooner.

SMi’s aim has always been to create a user-friendly, automated benchtop instrument that can be used in both research and healthcare settings. Initial instrument designs were guided by consultation with NHS trusts and the NIHR Medical Devices Testing and Evaluation Centre (MD-TEC), while prototypes have been tested in labs at the ̽��ֱ�� of Cambridge, the Medicines Discovery Catapult and the National Physical Laboratory. Commercial production will be outsourced to a medical device manufacturer in the East of England.

SMi’s CEO Dr Andrew Thompson said: “SMi is creating a highly accurate and user-friendly platform that is based upon single molecule imaging, meaning that we can detect individual molecules that are invisible to other technologies. With an approach that allows them to reliably monitor single molecules, SMi provides scientists and clinicians with a quality of data that is unprecedented. Such capabilities are likely to have far-reaching benefits for diagnosis and the discovery of new medicines. Our Innovate UK funding is allowing us to work with very highly qualified research and clinical partners, providing a means to accelerate our product development and realise these opportunities sooner.”

̽��ֱ��Cambridge Institute for Therapeutic Immunology and Infectious Diseases has been leading the ̽��ֱ�� of Cambridge’s collaboration with SMi. Ravindra Gupta, Professor of Clinical Microbiology, and named as one of Time Magazine’s 100 most influential people of the year in 2020 for his work on HIV, said: “SMi’s platform is incredibly exciting and could revolutionise testing for a range of diseases. We have been fortunate to partner with SMi on SARS-CoV-2 detection, and application could extend to identification of specific genetic variants of pathogens as well as cancers.”

Dr Tammy Dougan, Life Science and Healthcare Partnership Lead in the ̽��ֱ��’s Strategic Partnerships Office, said: “This is a great example of a Cambridge start-up winning Innovate UK funding and using it to build effective collaborations between research partners to take a new technology out of the lab and into clinical practice.”

Since 2018, SMi has grown into a team of sixteen, including scientists, mechanical engineers, software engineers and medical device specialists based in two locations: the outskirts of Cambridge and the West Coast of the USA.

Cambridge start-up SMi and its research partners have received two Innovate UK awards to progress their work on testing for infectious diseases and detecting biomarkers for cancer.

Andrew Brookes, Getty Images:

Pipetting sample into a tray

̽��ֱ��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.

Yes

Scientists publish first real-world data from Africa looking at immune response to AZ/Oxford COVID-19 vaccine

cjb250 — Wed, 11 May 2022 08:02:50 +0000

In a pre-print – which has yet to be peer-reviewed* – scientists from Nigeria and the UK analysed data from 140 healthcare workers at the Nigerian Institute of Medical Research and Federal Medical Center, Ebute Metta, and two private hospitals in Lagos. All participants had received two doses of the AstraZeneca vaccine administered between Jan and July 2021, with 12 weeks between doses.

According to the World Health Organization, around two-thirds of people in Africa are thought to have been exposed to SARS-CoV-2, the virus that causes COVID-19, with more than 250,000 deaths. Yet, since the rollout of the AstraZeneca COVID-19 vaccine in mid-2021, there has been no real world data on its effectiveness.

Vaccine rollout across the African continent has been mixed, with less than one in six (16%) of the eligible population receiving both doses and only around one in 75 (1.3%) receiving a booster dose.

̽��ֱ��team tested the participants, looking for evidence of antibodies specifically found in individuals who had previously been infected, rather than those raised by the vaccine. They initially found that 62 participants tested positive (44%).

In a subset of 49, they then tested serum samples taken from volunteers against pseudoviruses – synthetic viruses that mimic the behaviour of SARS-CoV-2 and its variants, but which are safe to study in the laboratory – to see whether vaccinated individuals were able to neutralise the virus.

̽��ֱ��team found that on average, one month after vaccination the Delta and Omicron variants required a 4.7-fold and 9.6-fold increase in the concentration of serum antibody in order to neutralise the virus, compared to the ‘wild type’ virus (the original strain). This indicates likely poor protection from infection by the Omicron variant, despite two doses of vaccine and infection before or during the study.

To look for evidence of vaccine breakthrough – where the virus is able to infect vaccinated individuals – the team looked at those individuals who had shown no evidence of previous infection and found that 14% became newly-infected between one and three months post-vaccination. This occurred during the Delta wave, and participants showed excellent immunity against Delta but persistently suboptimal immunity to Omicron.

Dr Adam Abdullahi, a Cambridge-Africa Research Fellow from the Institute of Human Virology, Abuja, Nigeria, and the ̽��ֱ�� of Cambridge, said: “Despite being the most widely-deployed vaccine, until now there’s been very little information on how effective the AstraZeneca vaccine is at protecting people in Africa from Omicron, nor even on levels of infections before and following vaccination using accurate lab tests.

“In our study, among healthcare workers in Nigeria, we found that nearly 50% had been infected prior to their first dose of the vaccine in early 2021.”

Professor Babatunde Lawal Salako, Director of the Nigeria Institute of Medical Research, Lagos, said: “There was some good news, in that the AstraZeneca vaccine was effective at protecting people against the virus, at least initially. But with the emergence of the Delta and Omicron variants, we were beginning to see the ability to neutralise the viruses fall, and almost one in five individuals who had received two doses were infected in the three months following vaccination. This could lead to severe disease in those with suppressed immune systems or who are medically vulnerable.”

Professor Ravi Gupta, lead investigator from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the ̽��ֱ�� of Cambridge added: “Given recent data suggesting that a third ‘booster’ dose with an mRNA vaccine increases and broadens protection against Omicron, we urgently need more longer term follow-up studies in west Africa, including trials of booster doses. If we are going to control this virus, we will only do so by ensuring that everyone eligible is protected against current and future variants that may be more pathogenic and severe.”

̽��ֱ��research was funded by NIMR, Lagos, Nigeria, Wellcome and the Africa Research Excellence Fund.

Reference
Abdullahi, A, Oladele, D, Kemp, SA, et al. Prior SARS COV-2 infection and immune responses to AZD1222 in West Africa. Pre-print released 5 May 2022

Updated 19 Oct 2022: ̽��ֱ��research has now been peer-reviewed and published in Nature Communications* (DOI: 10.1038/s41467-022-33792-x).

Scientists have released the first real-world data from Africa on the effectiveness of two doses of AstraZeneca/ChaAd0x-1 COVID-19 vaccination, showing that while protective against SARS-CoV-2, immunity against the Delta and Omicron variants was lower, even in the context of prior infection or infection after vaccination.

Despite being the most widely-deployed vaccine, until now there’s been very little information on how effective the AstraZeneca vaccine is at protecting people in Africa from Omicron

Adam Abdullahi

Jordi Sort Soler

3d digital image corona virus on planet Earth in Central Africa with clouds

Yes

Omicron may be significantly better at evading vaccine-induced immunity, but less likely to cause severe disease

cjb250 — Mon, 20 Dec 2021 15:37:40 +0000

As the SARS-CoV-2 virus replicates and spreads, errors in its genetic code can lead to changes in the virus. On 26 November 2021, the World Health Organization designated the variant B.1.1.529, first identified in South Africa, a variant of concern, named Omicron. ̽��ֱ��variant carries a large number of mutations, leading to concern that it will leave vaccines less effective at protecting against infection and illness.

Working in secure conditions, a team led by Professor Ravi Gupta at the Cambridge Institute of Therapeutic Immunology and Infectious Disease, ̽��ֱ�� of Cambridge, created synthetic viruses – known as ‘pseudoviruses’ – that carried key mutations found in the Delta and Omicron strains. They used these to study the virus’s behaviour.

̽��ֱ��team, which included collaborators from Japan, including Dr Kei Sato of the ̽��ֱ�� of Tokyo, has released its data ahead of peer review* because of the urgent need to share information relating to the pandemic, and particularly the new Omicron variant.

Professor Gupta and colleagues tested the pseudoviruses against blood samples donated to the NIHR COVID-19 BioResource. ̽��ֱ��blood samples were from vaccinated individuals who had received two doses of either the AstraZeneca (ChAdOx-1) or Pfizer (BNT162b2) vaccines.

On average, Omicron required around a ten-fold increase in the concentration of serum antibody in order to neutralise the virus, compared to Delta. Of particular concern, antibodies from the majority of individuals who had received two doses of the AstraZeneca vaccine were unable to neutralise the virus. ̽��ֱ��data were confirmed in live virus experiments.

Reassuringly, however, following a third dose of the Pfizer vaccine, both groups saw a significant increase in neutralisation.

Professor Gupta said: “ ̽��ֱ��Omicron variant appears to be much better than Delta at evading neutralising antibodies in individuals who have received just two doses of the vaccine. A third dose ‘booster’ with the Pfizer vaccine was able to overturn this in the short term, though we’d still expect a waning in immunity to occur over time.”

Spike proteins on the surface of SARS-CoV-2 bind to ACE2, a protein receptor found on the surface of cells in the lung. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. ̽��ֱ��virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

To see how effective Omicron is at entering our cells, the team used their pseudoviruses to infect cells in lung organoids – ‘mini-lungs’ that model parts of the lung. Despite having three mutations that were predicted to favour the spike cleavage, the researchers found the Omicron spike protein to be less efficient than the Delta spike at cleaving the ACE2 receptor and entering the lung cells.

In addition, once Omicron had entered the cells, it was also less able than Delta to cause fusion between cells, a phenomenon associated with impaired cell-to-cell spread. Fused cells are often seen in respiratory tissues taken following severe disease. Indeed, when the team used a live Omicron virus and compared it to Delta in a spreading infection experiment using lung cells, Omicron was significantly poorer in replication, confirming the findings regarding impaired entry.

Professor Gupta added: “We speculate that the more efficient the virus is at infecting our cells, the more severe the disease might be. ̽��ֱ��fact that Omicron is not so good at entering lung cells and that it causes fewer fused cells with lower infection levels in the lab suggests this new variant may cause less severe lung-associated disease.

“While further work is needed to corroborate these findings, overall, it suggests that Omicron’s mutations present the virus with a double-edged sword: it’s got better at evading the immune system, but it might have lost some of its ability to cause severe disease.”

However, Professor Gupta urged caution.

“Omicron still represents a major public health challenge. Individuals who have only received two doses of the vaccine – or worse, none at all – are still at significant risk of COVID-19, and some will develop severe disease. ̽��ֱ��sheer number of new cases we are seeing every day reinforces the need for everyone to get their boosters as quickly as possible.”

̽��ֱ��research was supported by Wellcome and the NIHR Cambridge Biomedical Research Centre.

Reference
Meng, B, et al. SARS-CoV-2 Omicron neutralising antibody evasion, replication and cell-cell fusion.

*Update: ̽��ֱ��research has now been peer-reviewed and is published in Nature as Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity (DOI: 10.1038/s41586-022-04474-x).

̽��ֱ��Omicron variant of SARS-CoV-2 may be significantly better than previous variants at evading vaccine-induced antibodies, according to new research from Cambridge – but preliminary evidence suggests it is less likely to cause severe COVID-19 illness in the lungs.

Omicron’s mutations present the virus with a double-edged sword: it’s got better at evading the immune system, but it might have lost some of its ability to cause severe disease

Ravi Gupta

Naeblys (Getty Images)

SARS-CoV-2 3D rendering

Yes

Cambridge scientists to take part in Royal Institution Christmas Lectures

cjb250 — Thu, 04 Nov 2021 14:34:12 +0000

Professors Julia Gog, Ravi Gupta and Sharon Peacock, each of whom have played a key role in the UK’s response to the on-going COVID-19 pandemic, will lead the on-screen exploration into their area of scientific expertise, with two Guest Lecturers appearing in each episode.

Together, they will offer insights to the Christmas Lectures’ young audience into the world of viruses – how they arise and proliferate, and how we humans respond – from testing and modelling to vaccine development and infection control. They will reveal why discoveries and advances made during the on-going pandemic will have an impact far beyond COVID-19 and are set to change the future of medicine.

̽��ֱ��Guest Lecturers will support the 2021 Christmas Lecturer Jonathan Van-Tam to demonstrate that tackling pandemics is a collaborative and interdisciplinary scientific effort.

Professor Julia Gog OBE, is Professor of Mathematical Biology at the Department of Applied Mathematics and Theoretical Physics at the ̽��ֱ�� of Cambridge and the David N. Moore Fellow and Director of Studies in Mathematics at Queens' College, Cambridge. During the pandemic she has contributed to scientific advice to the UK government through SAGE and SPI-M, the group which provides input based on infectious disease modelling and epidemiology.

Professor Ravi Gupta, is Professor of Clinical Microbiology at the Cambridge Institute for Therapeutic Immunology and Infectious Disease. Using his expertise in RNA virus genetics and biology, Ravi’s work during the pandemic has included reporting the first genotypic-phenotypic evidence for immune escape of SARS-CoV-2 within an individual, defining the process by which new variants are likely to arise, and defining the immune escape and transmissibility advantage of the Delta variant as the driver behind its global expansion.

Professor Sharon Peacock CBE, is Professor of Public Health and Microbiology in the Department of Medicine at the ̽��ֱ�� of Cambridge. During the pandemic Sharon has Chaired the COVID-19 Genomics UK (COG-UK) Consortium, delivering large-scale and rapid whole-genome virus sequencing to local NHS centres and the UK government, and helping to inform UK public health interventions and policies.

Also taking part as Guest Lecturers are:

Professor Katie Ewer, a cellular immunologist and Associate Professor at the Jenner Institute at the ̽��ֱ�� of Oxford.
Professor Teresa Lambe OBE, an Associate Professor based in the Oxford Vaccine Group at the ̽��ֱ�� of Oxford.
Professor Catherine Noakes OBE, Professor of Environmental Engineering for Buildings at the ̽��ֱ�� of Leeds.

Lucinda Hunt, Director of the Royal Institution, said: “We are delighted that Jonathan will be joined by such an exciting and expert group of scientists during this year’s series of three Christmas Lectures.

“They will work together to take us on a journey through the world of viruses – how they arise, how they proliferate, and how science and society responds – just as they are doing in tackling the current pandemic. What a strong and positive message that will be for our young audience, about the power of collaborative science.”

Patrick Holland, BBC Director, Factual, Arts and Classical Music Television, said: “Scientists across the world have responded to the Covid crisis with expertise and ingenuity that is humbling for us all. It is no exaggeration to say that the path of history has been changed because of the work of vaccine scientists and epidemiologists.

“Jonathan and his team will give us another exciting and thought-provoking series of Lectures, covering so much more than COVID-19. This will be a celebration of science and of the scientists whose advances are shaping our world.”

In the 2021 Christmas Lectures, ‘Going viral: How Covid changed science forever’, epidemiologist and one of England’s two Deputy Chief Medical Officers, Jonathan Van-Tam, will take a deep dive into many and varied viruses, including COVID-19, and reveal why discoveries and advances made during the on-going pandemic – from early detection techniques to new vaccines – mean biological science will never be the same again.

̽��ֱ��2021 Christmas Lectures will be broadcast on BBC Four and iPlayer between Christmas and New Year.

̽��ֱ��2021 Christmas Lectures are co-produced by the Ri and Windfall Films for BBC Four and iPlayer. They were commissioned by Patrick Holland, Director, Factual, Arts and Classical Music Television and Jack Bootle, Head of Commissioning, Science and Natural History. ̽��ֱ��Commissioning Editor for the BBC is Tom Coveney. The Series Producer is Henry Fraser and the Executive Producer is David Dugan.

Adapted from a press release by the Royal Institution

Three Cambridge researchers are among six leading UK scientists who will share the presenting duties with Professor Jonathan Van-Tam during this year’s Christmas Lectures from the Royal Institution.

Royal Institution

Audience at Royal Institution Christmas Lecture

Yes

Delhi outbreak highlights challenge of herd immunity in the face of Delta variant

cjb250 — Thu, 14 Oct 2021 18:00:35 +0000

SARS-CoV-2 had spread widely throughout India in the first wave, with initial results from the Indian Council of Medical Research finding one in five (21%) adults and one in four (25%) 10 to 17 year old adolescents had been infected. ̽��ֱ��figures were much higher in Indian megacities: by February 2021, over a half (56%) of individuals in Delhi were thought to have been infected.

Since the first case of COVID-19 was detected in Delhi in March 2020, the city had experienced multiple outbreaks, in June, September and November 2020. After reaching a high of almost 9,000 cases daily in November 2020, new cases steadily declined, with very few new infections between December 2020 and March 2021.

̽��ֱ��situation reversed dramatically in April 2021, going from approximately 2,000 daily cases to 20,000 between 31 March and 16 April. This was accompanied by a rapid rise in hospitalisations and ICU admissions, severely stressing the healthcare system, with daily deaths spiking to levels three-fold higher than previous waves.

In research published today, an international team of scientists used genomic and epidemiological data, together with mathematical modelling, to study the outbreak. ̽��ֱ��work was led by the National Centre of Disease Control and the CSIR Institute of Genomics and Integrative Biology, India, with collaborators from the ̽��ֱ�� of Cambridge and Imperial College London, UK, and the ̽��ֱ�� of Copenhagen, Denmark.

To determine whether SARS-CoV-2 variants were responsible for the April 2021 outbreak in Delhi, the team sequenced and analysed viral samples from Delhi from the previous outbreak in November 2020 until June 2021. They found that the 2020 outbreaks in Delhi were unrelated to any variant of concern. ̽��ֱ��Alpha variant (B.1.1.7) was identified only occasionally, primarily in foreign travellers, until January 2021. ̽��ֱ��Alpha variant increased in Delhi to about 40% of cases in March 2021, before it was displaced by a rapid increase in the Delta variant (B.1.617.2) in April.

Applying mathematical modelling to the epidemiological and genomic data, the researchers found that the Delta variant was between 30-70% more transmissible than previous SARS-CoV-2 lineages in Delhi, including the Alpha variant. Importantly, the model also suggested that the Delta variant was able to infect people who had previously been infected by SARS-CoV-2 – prior infection provided only 50-90% of the protection against infection with Delta variant that it provides against previous lineages.

To look for actual evidence of reinfection to support their modelling work, the researchers examined a cohort of individuals recruited by the Council of Scientific and Industrial Research (CSIR), India. In February, 42.1% of unvaccinated subjects participating in the study had tested positive for antibodies against SARS-CoV-2. In June, the corresponding number was 88.5%, suggesting very high infection rates during the second wave. Among 91 subjects with prior infection before Delta, about one-quarter (27.5%) showed increased levels of antibodies, providing evidence of reinfection.

When the team sequenced all the samples of vaccination-breakthrough cases at a single centre over the period of the study, they found that among 24 reported cases, Delta was seven-fold more likely to lead to vaccination breakthroughs than non-Delta lineages.

Dr Anurag Agrawal from the National Centre of Disease Control and the CSIR Institute of Genomics and Integrative Biology, India, senior author and co-lead investigator, said: “This work helps understand the global outbreaks of Delta, including in highly vaccinated populations, because the Delta variant can transmit through vaccinated or previously infected people to find those who are susceptible.”

Co-author Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the ̽��ֱ�� of Cambridge, UK, said: “ ̽��ֱ��concept of herd immunity is critical in ending outbreaks, but the situation in Delhi shows that infection with previous coronavirus variants will be insufficient for reaching herd immunity against Delta. ̽��ֱ��only way of ending or preventing outbreaks of Delta is either by infection with this variant or by using vaccine boosters that raise antibody levels high enough to overcome Delta’s ability to evade neutralisation.”

Previous research led by Professor Gupta showed that the Delta variant has most likely spread through its ability to evade neutralising antibodies and its increased infectivity.

̽��ֱ��research was supported by the Indian Ministry of Health and Family Welfare, Council of Scientific and Industrial Research, and Department of Biotechnology.

Reference
Mahesh Dhar, Robin Marwal, Radhakrishnan VS, Kalaiarasan Ponnusamy, Bani Jolly, Rahul Bhoyar, et al. Genomic characterization and Epidemiology of an emerging SARS-CoV-2 variant in Delhi, India. Science; 14 Oct 2021; DOI: 10.1126/science.abj9932

̽��ֱ��severe outbreak of COVID-19 in Delhi, India, in 2021 showed not only that the Delta variant of SARS-CoV2 is extremely transmissible but that it can infect individuals previously infected by a different variant of the coronavirus, say a team of international scientists writing in Science.

̽��ֱ��concept of herd immunity is critical in ending outbreaks, but the situation in Delhi shows that infection with previous coronavirus variants will be insufficient for reaching herd immunity against Delta

Ravi Gupta

Government of India

Health care workers administering COVID-19 vaccination in New Delhi

Yes

Licence type:

Attribution-Noncommerical

Spread of Delta SARS-CoV-2 variant driven by combination of immune escape and increased infectivity

cjb250 — Mon, 06 Sep 2021 14:47:55 +0000

̽��ֱ��Delta variant of SARS-CoV-2, which has become the dominant variant in countries including India and the UK, has most likely spread through its ability to evade neutralising antibodies and its increased infectivity, say an international team of researchers.

̽��ֱ��findings are reported today in Nature.

As SARS-CoV-2 replicates, errors in its genetic makeup cause it to mutate. Some mutations make the virus more transmissible or more infectious, some help it evade the immune response, potentially making vaccines less effective, while others have little effect. One such variant, labelled the B.1.617.2 Delta variant, was first observed in India in late 2020. It has since spread around the globe – in the UK, it is responsible nearly all new cases of coronavirus infection.

Professor Ravi Gupta from the Cambridge Institute of Therapeutic Immunology and Infectious Disease at the ̽��ֱ�� of Cambridge, one of the study’s senior authors, said: “By combining lab-based experiments and epidemiology of vaccine breakthrough infections, we’ve shown that the Delta variant is better at replicating and spreading than other commonly-observed variants. There’s also evidence that neutralising antibodies produced as a result of previous infection or vaccination are less effective at stopping this variant.

“These factors are likely to have contributed to the devastating epidemic wave in India during the first quarter of 2021, where as many as half of the cases were individuals who had previously been infected with an earlier variant.”

To examine how well the Delta variant was able to evade the immune response, the team extracted serum from blood samples collected as part of the COVID-19 cohort of the NIHR BioResource. ̽��ֱ��samples came from individuals who had previously been infected with the coronavirus or who had been vaccinated with either the Oxford/AstraZeneca or Pfizer vaccines. Serum contains antibodies raised in response to infection or vaccination. ̽��ֱ��team found that the Delta variant virus was 5.7-fold less sensitive to the sera from previously-infected individuals, and as much as eight-fold less sensitive to vaccine sera, compared with the Alpha variant - in other words, it takes eight times as many antibodies from a vaccinated individual to block the virus.

Consistent with this, an analysis of over 100 infected healthcare workers at three Delhi hospitals, nearly all of whom had been vaccinated against SARS-CoV-2, found the Delta variant to be transmitted between vaccinated staff to a greater extent than the alpha variant.

SARS-CoV-2 is a coronavirus, so named because spike proteins on its surface give it the appearance of a crown (‘corona’). ̽��ֱ��spike proteins bind to ACE2, a protein receptor found on the surface of cells in our body. Both the spike protein and ACE2 are then cleaved, allowing genetic material from the virus to enter the host cell. ̽��ֱ��virus manipulates the host cell’s machinery to allow the virus to replicate and spread.

Using 3D airway organoids – ‘mini-organs’ grown from cells from the airway, which mimic its behaviour – the team studied what happens when the virus reaches the respiratory tract. Working under secure conditions, the team used both a live virus and a ‘pseudotyped virus’ – a synthetic form of the virus that mimicked key mutations on the Delta variant – and used this to infect the organoids. They found that the Delta variant was more efficient at breaking into the cells compared with other variants as it carried a larger number of cleaved spikes on its surface. Once inside the cells, the variant was also better able to replicate. Both of these factors give the virus a selection advantage compared to other variants, helping explain why it has become so dominant.

Dr Partha Rakshit from the National Centre for Disease Control, Delhi, India, joint senior author, said: “ ̽��ֱ��Delta variant has spread widely to become the dominant variants worldwide because it is faster to spread and better at infecting individuals than most other variants we’ve seen. It is also better at getting around existing immunity – either through previous exposure to the virus or to vaccination – though the risk of moderate to severe disease is reduced in such cases.”

Professor Anurag Agrawal from the CSIR Institute of Genomics and Integrative Biology, Delhi, India , joint senior author, added: “Infection of vaccinated healthcare workers with the Delta variant is a significant problem. Although they themselves may only experience mild COVID, they risk infecting individuals who have suboptimal immune responses to vaccination due to underlying health conditions – and these patients could then be at risk of severe disease. We urgently need to consider ways of boosting vaccine responses against variants among healthcare workers. It also suggests infection control measures will need to continue in the post-vaccine era.”

̽��ֱ��research was largely supported in India by the Ministry of Health and Family Welfare, the Council of Scientific and Industrial Research, and the Department of Biotechnology; and in the UK by Wellcome, the Medical Research Council and the National Institute of Health Research.

Reference:
Micochova, P & Kemp, S et al. SARS-CoV-2 B.1.617.2 Delta variant emergence and vaccine breakthrough. Nature; 6 Sept 2021; DOI: 10.1038/s41586-021-03944-y

Findings suggest infection control measures against variants will need to continue in the post-vaccination era.

By combining lab-based experiments and epidemiology of vaccine breakthrough infections, we’ve shown that the Delta variant is better at replicating and spreading than other commonly-observed variants

Ravi Gupta

Fusion Medical Animation via Unsplash

Visualisation of the Covid-19 virus

Yes

̽��ֱ��virologist helping us to stay one step ahead of infectious diseases

cg605 — Tue, 10 Aug 2021 10:02:05 +0000

An established virologist specialising in the field of HIV drug-resistance, Ravi Gupta pivoted his expertise to address the COVID-19 pandemic. Over the last 18 months his pioneering research has helped us to stay one step ahead of emerging variants. He talks about his career as an infectious disease specialist and, in celebration of South Asian Heritage Month, what his heritage means to him.

̽��ֱ�� of Cambridge - Ravindra Gupta

Prioritise vaccine boosters for vulnerable immunocompromised patients, say scientists

Cambridge start-up wins funding to develop new diagnostics

Scientists publish first real-world data from Africa looking at immune response to AZ/Oxford COVID-19 vaccine

*Updated 19 Oct 2022: ̽��ֱ��research has now been peer-reviewed and published in Nature Communications (DOI: 10.1038/s41467-022-33792-x).

Omicron may be significantly better at evading vaccine-induced immunity, but less likely to cause severe disease

Cambridge scientists to take part in Royal Institution Christmas Lectures

Delhi outbreak highlights challenge of herd immunity in the face of Delta variant

Spread of Delta SARS-CoV-2 variant driven by combination of immune escape and increased infectivity

̽��ֱ��virologist helping us to stay one step ahead of infectious diseases

Updated 19 Oct 2022: ̽��ֱ��research has now been peer-reviewed and published in Nature Communications* (DOI: 10.1038/s41467-022-33792-x).