After UK approval, India panel ponders data of SII, Bharat Biotech for Covid-19 vaccine, nod likely next week

Hours after Britain approved the Oxford University-AstraZeneca COVID-19 vaccine, India’s expert panel met on Wednesday to review the data before submitting its final recommendation for approval. The entire process is likely to take a week and the announcement is likely to be known next week.

The Subject Expert Committee of the Central Drug Standard Control Organization (CDSCO) apparently pondered the data presented before it on Wednesday. The vaccine Covishield by SSI (Oxford-AstraZeneca) is a non- replicating viral vector vaccine with viruses that have been modified to act as delivery systems carrying the viral antigens to the body’s immune cells. Chimpanzee adenovirus is the vector used to deliver in this vaccine.

Once the application of Serum Institute of India for the same vaccine manufactured in India for emergency use authorization is approved, rollout will begin in a week’s period making India the second country to give EUA to the vaccine. Along with SII, Hyderabad-based Bharat Biotech had also applied for Emergency Use Authorization for its Covaxin and made its presentation on Wednesday before the experts panel.

Amid fears of new strain spreading rapidly, the UK became the first country in the world to approve the vaccine called Covishield, following a recommendation from the Medicines and Healthcare products Regulatory Agency (MHRA). Withthis, the rollout of mass vaccination is expected to begin in the first week of January in both the countries.

Vaccine-fda

Soon after the UK approval, AstraZeneca said in a statement that first doses of the vaccine will be released to begin the vaccinations drive and that the company hopes to supply millions of doses in the first quarter of 2021 as part of its deal with the UK government to supply up to 100 million doses in total. In India, SII is ready with 50 million doses of the vaccine already.

Earlier this month, the CDSCO had asked SII to submit the outcome of the assessment of UK-MHRA before granting emergency use authorization, updated safety data of the Phase II/III clinical trials and immunogenicity data from the clinical trial in UK and India.

Vaccination Drive

The central government plans to vaccinate nearly 30 crore people in the first phase, covering about one crore healthcare workers, about 2 crore frontline and essential staff besides 7 crore elderly, mostly above the age of 50 years with comorbidities.

SII CEO Adar Poonawalla on Monday said 40-50 million doses of COVID-19 vaccine have already been stockpiled, the rollout will be the New Year gift to the country that had witnessed severe health and financial crisis throughout the year 2020.  Together with Bharat Biotech, the two firms can produce 65 million doses of the vaccine per month.

Why WHO Optimistic About Oxford Covid-19 Vaccine? How Others Stack at AZD1222?

Finally, a Covid-19 vaccine developed by Oxford University’s Jenner Institute and licensed to the multinational pharmaceutical company, AstraZeneca has emerged as the favourite of World Health Organization scientists out of about 23 vaccines in their Phase III trial, after reporting success and safety in the first two phases.

For India, this vaccine is important as AstraZeneca, among others, had entered a deal with Pune-based Serum Institute of India to supply one billion doses for low-and-middle-Income countries, with first 400 million to be produced before the end of 2020. Its other global facilities will produce 300 million doses for the US.

Between April 23-May 21, Oxford University with AstraZeneca conducted human trials of the vaccine – where 1,077 volunteers were given the AZD1222 shot and all of them developed protective neutralizing antibodies as well as T-cells (T lymphocytes) which multiplied to attack any pathogen inside the human system. The participants were aged between 18 and 55 and split roughly 50-50 between male and female. Ninety-one percent of them were white, while roughly 5% were Asian, and fewer than 1% were Black.

While AZD1222 enters the next phase III of the clinical trials, the results published in The Lancet medical journal, show that the Covid-19 vaccine prompted no serious side effects among the people who received two doses so far, which has promted the WHO Chief Scientist Michael Ryan, the World Health Organization’s health emergencies chief to say: “We now need to move into larger scale, real-world trials, but it is good to see more data, more products moving in to this very important phase of vaccine discovery.” See the video below from 19:30 for WHO remarks on Oxford vaccine:

The next stage — Phase III — trial will be conducted in the US on 30,000 patients, besides those “in low-to-middle income countries including Brazil and South Africa which are already underway,” the university has said in a release.

Sarah Gilbert, professor of vaccinology at Oxford University, had earlier informed that 8,000 volunteers were enrolled for the Phase III trial which will assess how the vaccine works in a large number of people over the age of 18, and how well the vaccine works to prevent them from the infection. However, it will take a year to conclusively determine if the vaccine offers long-term protection or not.

“There is still much work to be done before we can confirm if our vaccine will help manage the COVID-19 pandemic… We still do not know how strong an immune response we need to provoke to effectively protect against Sars-Cov-2 infection,” said Gilbert.

Indian Serum Institute Role 

Pascal Soriot, chief executive of AstraZeneca, said the company was on track to be producing doses by September. While the Oxford University will have intellectual property rights, Pune-based Serum Institute of India will emerge as a major supplier.

The data, published in the medical journal the Lancet, showed that the vaccine caused side effects such as fever, headaches, muscle aches, and injection site reactions, in about 60% of patients, which are deemed mild and not dangerous for any vaccine.

The Oxford-AstraZeneca vaccine AZD1222 has finally emerged as a relatively safe vaccine in view of similar results or data from others is still awaited from 22 other contestants who are in Phase III trial. In case its immediate rival vaccine from the Chinese biotech CanSino, the Phase 2 results showed that this vaccine works better in some people and not equally efficient among those aged 55 and older, a key target for Covid-19 vaccination.

Advantages of Oxford vaccine over Moderna vaccine

While the AZD1222 vaccine went on trials from April 30 with a 10,000-patient study in the United Kingdom, another 5,000-patient test began in Brazil in June and the current phase 3 results could become available in September, October, or November, said Astra-Zeneca.

AZD1222 has another advantage as it needs to be kept cold, but not frozen, whereas the messenger RNA vaccines work on the body’s genetic messaging system to provoke an immune response. The mRNA vaccines, developed by Moderna, the German firm BioNTech and the drug giant Pfizer, increased levels of neutralizing antibodies in patients.

WHO Scientist Michael Ryan announcing the Oxford vaccine trial results at a press conference Monday, July 20, 2020 (WHO)

AZD1222 works differently using a genetically engineered virus, called adenovirus, which was taken from chimps and modified not to replicate and sicken people. It carries a gene for one of the proteins in SARS-Cov-2 and inserts it into a recipient’s cells, which in turn, cause the patient’s cells to make that protein, which is then recognized by the immune system as foreign. This mechanism was not there in the past but has been used in experimental vaccines such as the Ebola virus and the virus that causes Middle East respiratory syndrome (MERS).

Oxford vaccine vs CanSino

The next rival CanSino, also into its Phase 3 trial, is a viral vector vaccine that uses a live but weakened human cold virus, adenovirus 5 — known as Ad5 for short — to develop immune system of the body to recognize the SARS-CoV-2 coronavirus. Its focus is on the Ad5 parts of the vaccine rather than the SARS-Cov-2 and many research groups have stopped it over concerns about preexisting immunity, which can run to 70% or higher in some populations.

CanSino Phase 2 trial essentially showed that those who had no or low-level pre-existing immunity to Ad5 developed neutralizing antibodies to SARS-CoV-2 at roughly double the rate of people who had high-level preexisting immunity, especially in people aged 55 and older. CanSino has dropped the higher dose.

Kathryn Edwards, scientific director of the Vanderbilt Vaccine Research Program in Nashville, Tenn., noted the CanSino vaccine may not be protective enough for older adults, but it might be useful in children. However, the CanSino vaccine has already received an emergency license in China for use in the military.

Not China, but Russia announces world’s first Covid-19 vaccine

Any Covid-19 vaccine? All nations and the entire world humanity was eagerly awaiting the precious announcement from at least one top nation that its scientists have successfully completed clinical trials of Covid-19 vaccine.

When expectations were running high that it would be China, where the novel coronavirus had its origin in the city of Wuhan, unexpectedly Russia has announced first to the world that its clinical trials are completed successfully and the vaccine is ready for production.

The Sechenov First Moscow State Medical University is the one which has claimed that it has successfully completed the trails their vaccine has all the “safety of those vaccines that are currently in the market.”

Announcing the news, Vadim Tarasov, the director of the Institute for Translational Medicine and Biotechnology of the Unviersity said the clinical trials have been conducted on volunteers, reports Russian news agency Sputnik, adding that the first group of volunteers would be discharged on 15 July and the second on 20 July.

Russian vaccine

The vaccine was produced by Russia’s Gamalei Institute of Epidemiology and Microbiology on June 18. “Sechenov University has successfully completed tests on volunteers of the world’s first vaccine against coronavirus,” Tarasov said.

“The safety of the vaccine is confirmed. It corresponds to the safety of those vaccines that are currently on the market,” said another scientist Alexander Lukashev, director of the Institute of Medical Parasitology, Tropical and Vector-Borne Diseases at Sechenov University.

“Sechenov University in a pandemic situation acted not only as an educational institution but also as a scientific and technological research center that is able to participate in the creation of such important and complex products as drugs,” Tarasov said.

Elsewhere, Gilead Sciences, Oxford University’s researchers and American biotech company Moderna are at the forefront of developing a Covid-19 vaccine, while a Canadian and Chinese joint project is equally pushing the date for completion of clinical trials. BioNTech SE and Pfizer Inc’s Covid-19 vaccine candidate is expected to be ready by the end of 2020.

Coronavirus vaccine by October end, announces US pharma giant Pfizer

American pharmaceutical giant Pfizer has announced that its ongoing development of a COVID-19 vaccine could be ready in five months period by October end. Pfizer is working on the vaccine project in collaboration with German firm Biontech.

Pfizer and its vaccine development German partner BioNTech announced on Friday, May 29, that the first participants have been given the doses in the US in the Phase 1/2 clinical trial for the BNT162 vaccine program to prevent COVID-19. “If things go well, and the stars are aligned, we will have enough evidence of safety and efficacy so that we can have a vaccine around the end of October,” said Pfizer CEO Albert Bourla.

The trial is part of the dosing of the first cohort in Germany that was completed last week. The Phase 1/2 study is designed to determine the safety, immunogenicity and optimal dose level of four mRNA vaccine candidates under study. The dose level escalation portion (Stage 1) of the Phase 1/2 trial in the U.S. will enroll up to 360 healthy subjects into two age cohorts (18-55 and 65-85 years of age). The first subjects immunized in Stage 1 of the study will be healthy adults 18-55 years of age, said the company.

Older adults will be immunized with a given dose level once testing and dose level in younger adults has provided initial evidence of safety and immunogenicity. Currently,the participants are being given these doses at NYU Grossman School of Medicine and the University of Maryland School of Medicine, with the University of Rochester Medical Center/Rochester Regional Health and Cincinnati Children’s Hospital Medical Center.

“The short, less than four-month timeframe in which we’ve been able to move from pre-clinical studies to human testing is extraordinary and further demonstrates our commitment to dedicating our best-in-class resources, from the lab to manufacturing and beyond, in the battle against COVID-19,” said Albert Bourla, Chairman and CEO, Pfizer.

Pfizer and BioNTech’s Vaccine Program

Pfizer and BioNTech’s development program includes four vaccine candidates, each representing a different combination of mRNA format and target antigen. The ongoing trial allows for the evaluation of the various mRNA candidates simultaneously in order to identify the safest and potentially most efficacious candidate in a greater number of volunteers.

“It is encouraging that we have been able to leverage more than a decade of experience in developing our mRNA platforms to initiate a global clinical trial in multiple regions for our vaccine program in such a short period. We are optimistic that advancing multiple vaccine candidates into human trials will allow us to identify the safest, most effective vaccination options against COVID-19,” said CEO and Co-founder of BioNTech, Ugur Sahin, whose firm will provide the vaccine from its GMP-certified mRNA manufacturing facilities in Europe.

Once this stage is successfully accomplished, both Pfizer and BioNTech plan to rapidly increase production of millions of vaccine doses in 2020, increasing to hundreds of millions in 2021. BioNTech and Pfizer will work supply the vaccine worldwide once regulators allow except China, where BioNTech has a collaboration with Fosun Pharma for BNT162 for both clinical development and commercialization.

Pfizer-owned sites in three U.S. states (Massachusetts, Michigan and Missouri) and Puurs, Belgium are being pressed into  manufacturing COVID-19 vaccine production, with more sites to be selected once the vaccine rolls out. Through its existing mRNA production sites in Mainz and Idar-Oberstein, Germany, BioNTech plans to ramp up its production capacity.

US firm Inovio’s coronavirus vaccine trial on mice turns positive

US vaccine maker Inovio Pharmaceuticals said on Wednesday that its experimental vaccine to prevent coronavirus infection produced protective antibodies and immune system responses in mice and guinea pigs, raising hopes that it could provide relief if Moderna’s vaccine fails.

The company’s shares, which have more than quadrupled this year on hopes of its vaccine working, surged another 18% to $15.77 in early trading, reports Reuters.

“We saw antibody responses that do many of the things we would want to see in an eventual vaccine,” said Dr. David Weiner, director of the immunotherapy center at the Wistar Institute, which has collaborated with Inovio. “We are able to target things that would prevent the virus from having a safe harbor in the body.”

There are currently no approved treatments or vaccines for COVID-19, and more than 100 vaccines are under trials across the world, with more than 12 to 18 months to develop one effective vaccine among the candidates.

Apart from Inovio, other drug makers such as Moderna, Pfizer, Johnson & Johnson, Sanofi and AstraZeneca are in various stages of vaccine development. On Monday, Moderna said its experimental COVID-19 vaccine produced protective antibodies in a small group of healthy volunteers.

Inovio said preliminary results from its human trial are expected in June. The 40 healthy participants in the Phase 1 trial are given two shots, four weeks apart, of the vaccine, called INO-4800, and then followed for two weeks.

“We are already seeing safety data and it has been benign,” Dr. Katherine Broderick, head of research and development at Inovio, told Reuters. “Some people have slight redness of the arm.”

Both Moderna and Inovio are focusing on specific genes on the outer “spike” portion of the virus for vaccine. Inovio’s vaccine was designed using its DNA medicine platform, while Moderna’s vaccine uses messenger RNA (mRNA) technology. Once the preliminary data is in, Inovio will seek FDA approval to move into a Phase 2/3 trial, which could happen in July or August.

SARS-CoV-2: New coronavirus but there’s a cure in old bottle

Important lessons learned from the Severe Acute Respiratory Syndrome (SARS) outbreak of 2002-2003 could inform and guide vaccine design for COVID-19 according to University of Melbourne Professor Kanta Subbarao, Director of the WHO Centre for Reference.

Neutralising antibodies prevent infection by binding to a virus and blocking their ability to infect. After an infection, a host can produce neutralising antibodies to protect against future infection. “The speed with which SARS-CoV-2, the virus that causes COVID-19, has spread around the world and its toll in numbers of cases, severe illness, and death has been staggering,” she said.

“However, technological advances have made rapid vaccine development possible. We have to ask ourselves what the new vaccines should aim to achieve – prevent all infection or prevent severe disease and death? In which age group(s)? What effect will vaccines that address these choices have on subsequent epidemics?”

How they worked on SARS in 2003?

Professor Subbarao was the Chief of the Emerging Respiratory Viruses Section of the Laboratory of Infectious Diseases at the National Institute for Allergy and Infectious Disease at the US National Institutes of Health during the SARS outbreak in 2002-2003, and was central to an important discovery of how neutralising antibodies protect from infection.

Halden’s technique boasts high sensitivity, with the potential to detect the signature of a single infected individual among 100 to 2 million persons. To accomplish this, wastewater samples are screened for the presence of nucleic acid fragments of the SARS-CoV-2 virus. The RNA genomes are amplified through a process known as reverse-transcriptase quantitative PCR (RT qPCR) / CREDIT: Shireen Dooling

“We used mouse experiments to establish the very important principle that neutralising antibodies alone were sufficient to protect them from SARS-CoV infection,” Professor Subbarao described.

She also explained the crucial discovery that the ‘spike’ protein of the virus induced neutralising antibodies, and the importance of animal trials of several SARS vaccine candidates. Coronavirus particles have a corona (crown) of spike proteins that allow the virus to attach and enter cells.

“The ‘spike’ proteins of both SARS-CoV and SARS-CoV-2 are related and they attach to the same molecule called ACE 2 on human cells to infect people. We now also know through animal experiments with SARS-CoV-2 that neutralising antibodies protect from reinfection,” Professor Subbarao said.

“Two SARS vaccines were evaluated in humans, and a number of promising candidates were tested in pre-clinical studies, but they weren’t pursued because SARS didn’t re-emerge. “However, the work on SARS is relevant to the COVID-19 pandemic because the two viruses share several features and many of the principles and experience with SARS vaccines will apply to SARS-CoV-2.”

AstraZeneca UK to produce vaccine after tie-up with Oxford University

AstraZeneca Plc agreed to make an experimental coronavirus vaccine developed by Oxford University researchers as the race for vaccine heats up. In India, the Serum Institute, the world’s largest maker of vaccines by volume, has already started producing millions of doses of the Oxford University shot and it remains to be seen whether market share will be entered at a later stage depending on the availability of the vaccine.

Astra has a capacity to produce 100 million doses by the end of the year, said the company, which is gearing up for a tough competition with a dozen other competitors across the world. UK-based AstraZeneca announced partnership with the University of Oxford on Thursday to help develop, produce and distribute a potential COVID-19 vaccine as a solution to the deadly disease.

UK Business Secretary Alok Sharma welcomed the tie-up as a vital step while a team of British scientists last week administered first vaccine doses to volunteers. “Our hope is that, by joining forces, we can accelerate the globalisation of a vaccine to combat the virus and protect people from the deadliest pandemic in a generation,” AstraZeneca Chief Executive Pascal Soriot said.

The vaccine “ChAdOx1 nCoV-19” is being developed by the Jenner Institute and Oxford Vaccine Group. The AstraZeneca-Oxford partnership is looking to provide vaccine inside the UK by the end of the year. Cambridge-based AstraZeneca is also testing two other treatments for coronavirus that has so far infected over 3 million people and killed more than 215,000 worldwide.

The shares of the company rose 2% on London’s FTSE by 9:30 am Friday, outpacing rival GSK. Apart from AstraZeneca. GSK and Sanofi are the other major players working on their own vaccine. Other major drugmakers testing possible COVID-19 vaccines include Pfizer, Moderna, Johnson & Johnson and Novavax. Nearly, 100 vaccines are in the pipeline at various stages of initial trials around the world and scientists say it may take another year for the right vaccine to emerge successfully.

The Indian vaccine being developed by the Serum Institute is a recombinant viral vector vaccine using a weakened version of the common-cold virus spiked with proteins from the novel coronavirus to trigger a response from the body’s immune system.