The world is yet to recover from Covid-19, and new vaccines are being developed in different countries. After the first cases came to light in Wuhan, China in December 2019 and the shocking global spread of the disease, the need for a vaccine was felt.
On January 11, 2020, the genetic sequence of Covid-19 was published for the first time, and various international pharmaceutical companies, biotechnology majors and research labs came together to work on developing a vaccine. A multinational collaboration, including the World Health Organization (WHO), the Coalition for Epidemic Preparedness Innovations (CEPI), GAVI, the Gates Foundation, and governments, formed the Access to Covid-19 Tools (ACT) Accelerator, to raise financial support of accelerated research and development, production, and globally-equitable access to COVID-19 tests, therapies, and licensing of vaccines, which are in a specific development program called the “COVAX Pillar”
According to the World Health Organization (WHO), “There are currently more than 50 Covid-19 vaccine candidates in trials. WHO is working in collaboration with scientists, business, and global health organisations through the ACT Accelerator to speed up the pandemic response. When a safe and effective vaccine is found, COVAX (led by WHO, GAVI and CEPI) will facilitate the equitable access and distribution of these vaccines to protect people in all countries. People most at risk will be prioritised.”
Here’s a quick look at five of the vaccines that have either gained approval for release to the general population or are close to it: who is developing them, what stage of trial they are in and if any concerns have been raised about them.
Pfizer-BioNTech vaccine
This vaccine was greenlighted by the United States government after much drama on December 11,2020. The White House had reportedly threatened to fire Food and Drug Administration (FDA) chief Stephen Hahn if he did not grant emergency approval. The death toll due to Covid-19 in US is getting close to 3,00,000.
Thevaccine has already been authorized in UK, Bahrain and Canada. According to a statement issued by Pfizer-BioNTech on November 9 to announce the results of first interim analysis from phase 3 of the study, “Vaccine candidate was found to be more than 90% effective in preventing Covid-19 in participants without evidence of prior SARS-CoV-2 infection in the first interim efficacy analysis.” They added, “Analysis evaluated 94 confirmed cases of Covid-19 in trial participants,”and that the study “enrolled 43,538 participants, with 42% having diverse backgrounds, and no serious safety concerns have been observed.”
However, FDA had recently raised concerns about the vaccine at a Vaccines and Related Biological Products Advisory Committee meeting on December 10, 2020. According to the briefing document, “Among non-serious unsolicited adverse events, there was a numerical imbalance of four cases of Bell’s palsy in the vaccine group compared with no cases in the placebo group, though the four cases in the vaccine group do not represent a frequency above that expected in the general population.”
It added, “Bell’s palsy was reported by four vaccine participants and none in the placebo group. These cases occurred at 3, 9, 37, and 48 days after vaccination. One case (onset at 3 days postvaccination) was reported as resolved with sequelae within three days after onset, and the other three were reported as continuing or resolving as of the November 14, 2020 data cut-off with ongoing durations of 10, 15, and 21 days, respectively. The observed frequency of reported Bell’s palsy in the vaccine group is consistent with the expected background rate in the general population, and there is no clear basis upon which to conclude a causal relationship at this time, but FDA will recommend surveillance for cases of Bell’s palsy with deployment of the vaccine into larger populations.”
The entire briefing document may be read here:
Also, given how this vaccine needs to be stored at -70 degrees Celsius temperature, concerns are being raised about how well it can be stored in hot weather countries like India.There are also concerns regarding the high cost of the vaccine in India. The manufacturers can reportedly produce 50 million doses during 2020 and 1.3 billion doses during 2021. Pfizer already has orders from Australia, Canada, the European Union, Japan, Peru, Qatar, Singapore, the UK and the US.
Moderna’smRNA-1273 vaccine
This vaccine was co-developed by the Cambridge, Massachusetts-based biotechnology company Moderna, Inc., and the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), UK.
According to the NIH, “More than 30,000 participants at 100 clinical research sites in the United States are participating in the study, which launched on July 27, 2020, after results from earlier stage clinical testing indicated that the vaccine candidate is well-tolerated and immunogenic.”
In a statement released on November 16, the NIH said, “An independent data and safety monitoring board (DSMB) overseeing the Phase 3 trial of the investigational Covid-19 vaccine known as mRNA-1273 reviewed trial data and shared its interim analysis with the trial oversight group on Nov. 15, 2020. This interim review of the data suggests that the vaccine is safe and effective at preventing symptomatic Covid-19 in adults.” They further said, “The interim analysis comprised 95 cases of symptomatic Covid-19 among volunteers. The DSMB reported that the candidate was safe and well-tolerated and noted a vaccine efficacy rate of 94.5%. The findings are statistically significant, meaning they are likely not due to chance. 90 of the cases occurred in the placebo group and 5 occurred in the vaccinated group. There were 11 cases of severe Covid-19 out of the 95 total, all of which occurred in the placebo group.”
Moderna applied for emergency FDA approval, but even before that the US government had purchased 100 million doses of the vaccine. On December 11, it was announced that an order was placed for another 100 million doses. Health and Human Services Secretary Alex Azar said, “Securing another 100 million doses from Moderna by June 2021 further expands our supply of doses across the Operation Warp Speed portfolio of vaccines.” A panel will convene to decide on the grant of emergency approval to Moderna’s vaccine on December 17. About 20 million doses could be available in the US in December itself. It could also be approved in Canada and UK soon.
So far, no serious adverse effects to the vaccine have been reported by trial participants. According to Science Magazine, “The independent board that conducted the interim analysis of Moderna’shuge trial found that severe side effects included fatigue in 9.7% of participants, muscle pain in 8.9%, joint pain in 5.2%, and headache in 4.5%.”
Oxford-Astra Zeneca vaccine
This is the third most watched Covid-19 vaccine, especially in wake of reports of alleged errors and severe side effects. It is being developed jointly by Oxford University’s Jenner Institute and pharma major Astra Zeneca. Currently clinical trials are underway in Brazil, South Africa, UK and USA. In India, trials are being conducted by the Serum Institute of India (SII) in association with the Indian Council of Medical Research (ICMR) at the Sri Ramachandra Institute of Higher Education and Research in Chennai.
However, this particular vaccine is the one that has attracted the maximum amount of controversy. First, there was an error in administering dosage to trial participants that led to wrong results for efficacy. Trial participants were to be administered two doses, however, the first time they were administered the dose, it was just half the dose, instead of a full dose. This led to calculation errors and inaccurate results.
When the interim trial results were made public in a press release about a fortnight ago, the researchers reported three efficacy levels for the vaccine – an overall effectiveness of 70%, a lower one of 62% and a high of 90%.
However, interestingly, this mistake in dosage apparently produced the best results. According to BBC, “Some volunteers were given shots that were half the strength than originally planned.Yet that “wrong” dose turned out to be a winner – giving 90% protection – while two standard doses gave 62%.”
Nature Journal observed, “Researchers have struggled to explain how a higher efficacy could be achieved from a lower initial dose, and trial investigators have said that a separate trial is needed to follow up on the finding. Furthermore, the low-dose arm of the trial did not include anyone over the age of 55, raising concerns that the higher efficacy was merely a by-product of excluding an age group that is particularly vulnerable to Covid-19.” On the subject of asymptomatic infections, it further observed, “The data show that the low-dose vaccine regimen was about 60% effective at reducing asymptomatic infections, but it is unclear whether the standard dose significantly reduced them at all.”
According to The Lancet Journal that published on December 8, 2020, the result of an interim study based on results from two of the four ongoing trials in UK and Brazil, “Serious adverse events were evaluated in 12 174 ChAdOx1 nCoV-19 recipients and 11 879 control recipients. No serious adverse events or deaths that were treatment associated occurred in ChAdOx1 nCoV-19 recipients. There were 175 serious adverse events (84 in the ChAdOx1 nCoV-19 group and 91 in the control group), three of which were possibly related to the intervention: transverse myelitis occurring 14 days after a ChAdOx1 nCoV-19 booster vaccination, haemolytic anaemia in a control recipient, and fever higher than 40°C in a participant still masked to group allocation. Two additional transverse myelitis cases considered unlikely to be related to the intervention occurred: one 10 days after the first dose of ChAdOx1 nCoV-19 was attributed to pre-existing multiple sclerosis and one in a control group that occurred 68 days after vaccination. The transverse myelitis cases resulted in temporarily pausing the trial and all participants have recovered or are recovering.”
However, the Oxford vaccine has attracted attention in India when in November 2020, a 40-year-old man who allegedly suffered an adverse reaction while participating in the clinical trial, sued the Serum Institute of India (SII) demanding Rs 5 crores as damages. The man claimed to have suffered headaches, nausea, memory loss and even allegedly went into a coma like state briefly after participating in the clinical trial. Concerns are also being raised about the efficacy of the vaccine in people over 65 as they are most susceptible to Covid-19 on account of greater likelihood of comorbidities.
SputnikV
The vaccine is named after the first Soviet space satelliteSputnik-1 that was launched in 1957. This Russian vaccine is based on a well-studied human adenoviral vector-based platform. It is administered in two doses with a gap of 21 days.
It was the first registered vaccine and at present is being offered to doctors, teachers and social workers in Russia. Unlike the Pfizer vaccine that needs to be stored at -70 degrees Celsius, the Sputnik V needs to be stored at -18 degrees Celsius.
Sputnik V was in the news recently when it was announced that the Astra Zeneca vaccine will test using a component of Sputnik V in its clinical trials. According to their official website, “The unique feature of the Russian vaccine is the use of two different components based on human adenovirus in two separate inoculations in order to deliver genetic material from the spike of the coronavirus into the human body. This approach provides for a stronger and longer-term immune response compared with vaccines using the same component for both inoculations.On November 23, 2020, following results which showed high efficacy for the Sputnik V vaccine, RDIF and the GamaleyaCenter offered AstraZeneca the use of one of the two components of the Sputnik V vaccine.AstraZeneca accepted the proposal by RDIF and the GamaleyaCenter to use one of the two vectors of the Sputnik V vaccine in additional clinical trials of its own vaccine, which will commence before the end of this year.”
Russian Direct Investment Fund (RDIF) is Russia’s sovereign wealth fund established in 2011 to make equity co-investments, primarily in Russia, alongside reputable international financial and strategic investors. RDIF acts as a catalyst for direct investment in the Russian economy.
The ongoing Sputnik V post-registration clinical trial in Russia involves 40,000 volunteers.Clinical trials of Sputnik V have been announced in the UAE, India, Venezuela and Belarus. The manufacturer claims, “The efficacy of the Sputnik V vaccine is 91.4%, based on the second interim analysis of data obtained 28 days after administering the first dose (7 days after the second dose).”
Sputnik V has reportedly been requested by over 50 countries and the vaccine supplies for the global market will be produced by RDIF’s international partners in India, Brazil, China, South Korea and other countries.
Though some concerns were raised about alcohol consumption after taking the vaccine, those were shot down by the manufacturer shortly afterwards.
However, Julie McElrath from the Fred Hutchinson Cancer Research Center has raised concerns over using Ad5 as a vehicle for Covvid-19 vaccines. Sciencemag reports this was due to Ad5 being“linked to a catastrophe in an HIV vaccine study 13 years ago. In that trial, vaccine recipients had higher rates of HIV infection than those in the placebo group; the Ad5 vector has become the leading suspect for the problem.” Therefore, now concerns are being raised about testing the vaccine in populations with a high prevalence of HIV.
Lawrence Corey of the Fred Hutchinson Cancer Research Center told Sciencemag, “If I were in a sub-Saharan African country and making a decision as to what I would want for my country for a general population use of a SARS-CoV-2 vaccine, I don’t see why I would pick an Ad5 vector [vaccine] when there are many other alternative choices.”
Covaxin
This is India‘s indigenous Covid-19 vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR) and the National Institute of Virology (NIV). According to the manufacturers, “It is a highly purified and inactivated vaccine, manufactured in a vero cell manufacturing platform.”
The vaccine received DCGI approval for Phase I & II Human Clinical Trials and the trials commenced across India from July, 2020. Phase 3 was kicked off to include 26,000 participants at 25 locations across India in Bhubaneshwar, Delhi, Mumbai, Guntur, Bhopal, Ahmedabad, Aligarh, Hyderabad, Rohtak and Goa.
However, recently concerns were raised about its efficacy when Haryana Health Minister Anil Vij tested Covid positive after taking the vaccine. It was only on November 20, that Vij had volunteered to be the first to get a shot Covaxin, when the third phase trial started in the state.
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