Introduction – “Vaccines the only hope!”
There are more than 4,010,834 confirmed deaths, 458,355 new cases and 185,291,530 confirmed case according to the (WHO Dashboard) at the time of writing this page.
According to most authorities the main method of fighting this pandemic is to vaccinate the worlds population as quickly as possible. The other methods such wearing a face mask, social distancing and hand washing has been given much lower weightage in controlling the pandemic, although these are the measures that will minimize the spread until instantly when the worlds population go about and do their day-to-day business until they get vaccinated and the immunity builds up in weeks or month. Furthermore it is not certain how long the immunity will be maintained and when it will be necessary to have a booster dose. Already some companies have suggested a booster dose.
The emergence of variant strains further emphasizes the need to quickly control viral replication and transmission, through public health practices of masking, social distancing and testing, and by vaccinating the global population as rapidly as possible.
The production of Covid-19 vaccines is crucial to the world at this point in time and is a huge multinational business mainly involving the western countries led by the US, UK & Europe. China, India, Cuba is outside the western circle and may be introduced as the opposition. This business of vaccine production may be the most single important business venture now and the profits and loss are enormous.
Multiple manufacturers are needed to meet the enormous global demand for COVID- 19 vaccines and to achieve high global vaccine coverage.
Covid-19 vaccines: In the rush for regulatory approval, do we need more data?
Pfizer CEO Albert Bourla said the company’s data “confirm the favourable efficacy and safety profile of our vaccine and position us to submit a Biologics License Application to the US FDA [Food and Drug Administration].” 1 And on 7 May it formally initiated that application which, if successful, will earn the Pfizer-BioNTech product, BNT162b2, the distinction of becoming the first covid-19 vaccine approved by the FDA.
Because lest we forget, all covid-19 vaccines currently in use in the US are available under emergency access only. The situation is similar in Europe, where four covid-19 vaccines have been granted “conditional marketing authorisations,” a fast track mechanism that can be used in emergencies. These can be converted into standard “marketing authorisations” pending positive data after authorisation, but this has not yet happened for any covid-19 vaccine being administered.
The FDA had already come under fire, accused of bending to the White House in granting EUAs for two covid-19 treatments, hydroxychloroquine and convalescent plasma. But those fears largely dissipated when the FDA published a guidance document in early October outlining its expectations for the EUA. According to the document, at least half of a trial’s participants would need to be followed for at least two months.7 This alone made it all but certain no vaccine could cross the line before the US election.
Six months: enough? One key difference between EUA and approval (also called “licensure,” and which for vaccines is known as a BLA (Biologics License Application)) was the expected length of follow-up of trial participants. Unlike its clear articulation of two months for an EUA, the FDA has not committed to a clear minimum for approval
Some experts warn “Is it possible to predict or estimate when conditions of safety and efficacy might be satisfied for BLA?” They asked the FDA . Teh FDA experts replied “I couldn’t predict, but I will say that we typically ask for at least six months of follow-up in a substantial number of clinical trial participants to constitute a safety database that would support licensure.” An approval based on six months of data would represent one of the fastest for a novel vaccine in FDA history. Among the six “first in disease” vaccines approved by the FDA since 2006, pre-licensure pivotal trials were a median of 23 months in duration, according to a recent analysis.
Are some COVID vaccines better than others? Interpreting and comparing estimates of efficacy in trials of COVID-19 vaccines – (MedXRview)
COVID-19 vaccine trials provide valuable insight into the safety and efficacy of vaccines, with individually-randomized, placebo-controlled trials being the gold standard in trial design. However, a myriad of variables must be considered as clinical trial data are interpreted and used to guide policy decisions. These variables include factors such as the characteristics of the study population and circulating SARS-CoV-2 strains, the force of infection, the definition and ascertainment of endpoints, the timing of vaccine efficacy assessment, and the potential for performance bias.
Thus far, efficacy estimates against symptomatic illness for both mRNA vaccines tested in the U.S. have far exceeded the FDA minimum criteria of 50%. While these high point estimates of efficacy are impressive, the most important measures of vaccine impact from the public health standpoint are number of cases, and severe cases, prevented. Peer-reviewed data from U.S. studies of non-mRNA vaccines are pending, although data available from other countries or through press release strongly suggest that spike glycoprotein based constructs will markedly reduce severe disease outcomes.
Variant strains have been recognized since early in the pandemic and emerged before introduction of vaccines. The cross-protective effects of vaccination as measured by early immunogenicity and disease outcomes are reassuring, albeit imperfect [11, 23]. How vaccines will affect future virus evolution is unknown.
On of the best things that happened to the World is the COVAX program.
Tamiflu (Oseltamivir) and Roche profits
Past experience teaches that particularly in healthcare, larger the profits, more irregularities, distortion or suppression of facts will be done by the top most pharmaceutical companies with the know or unknown corporation of world organisations such as WHO and CDC. The best recent example that was involved in billions of dollar (estimated to be over 18 billion US $) transaction happened because of stockpiling of Tamiflu (Oseltamivir). BMJ editorial in 2017 describes the lessons to learn which is weell summarized by the UK House of commons: ” This longstanding regulatory and cultural failure impacts on all of medicine, and undermines the ability of clinicians, researchers, and patients to make informed decisions about which treatment is best.” Read the complete article why WHO finally downgraded the status of Tamiflu (Oseltamir)
Why you can’t compare Covid-19 vaccines – at least for now
Comparison of COVID-19 Vaccine Approvals at the US Food and Drug Administration, European Medicines Agency, and Health Canada – JAMA 2021 June
Are some COVID vaccines better than others? Interpreting and comparing estimates of efficacy in trials of COVID-19 vaccines
WHO downgrades status of oseltamivir
Important lessons from the Tamiflu story
Oseltamivir (Tamiflu) was approved by the US Food and Drug Administration in 1999 for the treatment of uncomplicated influenza within 48 hours of the onset of symptoms. The manufacturer’s press release stated that the drug was studied in two randomised trials enrolling a total of 849 patients with influenza and reported a 1.3 day mean reduction in the duration of symptoms.1 The drug was described as safe, with less than 1% of patients discontinuing it because of adverse effects. It was approved by the European Medicines Agency in 2002.2
On the basis of these limited (and ultimately revealed as incomplete) data, governments acted. Concerned about a possible outbreak of avian influenza, as well as the H1N1 pandemic in 2009, the UK government stockpiled oseltamivir at a cost of over £600m (€680m; $770m) from 2006 to 2014. Similarly, the US government has spent over $1.5bn stockpiling the drug, based on recommendations from the Centers for Disease Control and Prevention (CDC).3 And in 2010, in the wake of the worldwide pandemic of H1N1 influenza, oseltamivir was added to the World Health Organization’s list of essential medications.4 This list is intended to guide decisions on national formularies and should include only “the most efficacious, safe, and cost effective medicines for priority conditions.” As a result, oseltamivir has been described as “a nice little earner,” generating over $18bn in sales worldwide, half of it from governments stockpiling the drug.5
Coronavirus: COVID-19 vaccine side-effects vs. the risk of infection – from Times of India
01/9 Which COVID-19 vaccine should you go for right now?
Vaccination drives have been ramped up across the country and now, there are more vaccines available for use. With the latest approval being granted to Moderna Inc’s, novel mRNA vaccine, India now has 4 vaccines in its ambit.
While we await more news regarding the availability of Moderna’s and Sputnik V vaccines, the wide-scale availability will help cover up shortages and reach a larger population in the stipulated time. Even so, the availability of different vaccines now will offer people a wider choice of vaccines during these trying times.
02/9 If you have the choice, which vaccine should you choose?
Each vaccine we have, passes the WHO standard of approval, has tolerable efficacy rates and mitigates dangers. Yet, some may be more reliable than others and carry benefits too. So, when you have the choice- what should you pick?
If you are yet to get vaccinated, here’s a comparison of the different vaccines we have…
03/9 How are the vaccines made?
The four vaccines which have received emergency use authorisation (EUA) in India are all made using different platforms.
While the Covishield jab (Oxford-Astrazeneca) vaccine is a viral vector vaccine that uses an adenovirus found in Chimpanzees, ChAD0x1, to deliver spike proteins and mount a tolerable immune response in response to a live virus. Covaxin, developed and manufactured in India uses a similar inactive viral strain. Both of them are made using traditional vaccine-build platforms.
Sputnik V uses a weakened strain of the common cold virus, adenovirus, which is then used to spike a tolerable immune response.
Moderna’s COVID vaccine, which was one of the first ones to be approved for use globally, is made using an innovative mRNA technology (messenger RNA) that instructs the cells to build a harmless fragment of the spike protein, similar to the actual coronavirus and prompt an immune response. mRNA vaccines are considered a new-age technology, with its set of benefits and considered to be more successful. However, the use of traditional technology vaccine platforms makes for a safer choice at the same time, which is more reliable and hence, has a lot of takers.
It should be noted that in the coming weeks, India might also have access to another COVID-19 vaccine, built using a completely different platform, plasma DNA, which will be the first-of-its-kind vaccine in the world. The DNA COVID vaccine, developed by Indian pharma major Zydus Cadila, is subject to approval and use.
04/9 Efficacy rate
The efficacy rate determines the workability of a given COVID-19 vaccine under clinical settings and showcases how potent it could be, once approved. Now, all four vaccines that we have passed the WHO nod for approval, which state that a vaccine should be at least 50% efficacious against transmission.
However, from what has been seen, clinical trials and real-time usage have suggested that all the vaccines, while effective against the SARS-COV-2 strain, have different efficacy rates. The higher the efficacy rate may promise a coronavirus vaccine more favorability and usage as well. In the current scenario we have, the four vaccines offer different efficacy rates.
Covishield vaccine, which was the first to be approved for use in India has a proven efficacy rate of 70%, which can be scaled up to 91% when both doses are administered 8-12 weeks apart. The vaccine also mounts a higher antibody response and prevents severe outcomes. Covaxin, which recently completed the third stage of trials shows an efficacy rate of 78%, additionally providing 100% protection against severity and mortality.
The third COVID-19 vaccine that we have, Sputnik V, according to the RDIF demonstrates an efficacy rate of 78.6% to 83.7%, as per trials and case studies conducted.
Of all, Moderna’s hopeful COVID-19 shot, mRNA-1273, has been found to be the most efficacious of all. While the company wrapped up trials in December, it has been found that the vaccine has an efficacy rate of over 91%, with immunity peaking after administering two doses. The company is also in the middle of conducting trials on kids below the age of 16 and interim data has proven that the vaccine is just as effective when used pediatrically.
05/9 Workability against the Delta variant
When we talk of a vaccine’s efficacy and effectiveness, in the current timelines, it becomes all the more crucial to study how effective a vaccine would be against the mutant strains of SARS-COV-2 which are fast spreading and have been categorized as Variants of Concern (VoCs). As we have seen, there was a rise in cases amongst those who had been vaccinated earlier- meaning that the vaccines we have, may not be as effective as proven.
Although the vaccines are subject to many levels of evaluation, and may even need upgrades as we move forward, some of the vaccines have proven to be less effective and efficacious against the Delta variant. Covishield’s efficacy rate has been seen to drop to 65% with the Delta variant, whereas recent studies have proved a similar drop in the workability of Covaxin as well (61%). With Sputnik V, too, there is a fall, but according to experts, the fall could be insignificant.
As for Moderna’s make, recent evaluations have proved that the vaccine is well able to neutralize antibodies against such VoCs, and offers a good level of protection as well, at a lower efficacy rate. Therefore, the ability of the mRNA vaccine to combat Delta and other variants of COVID-19 may offer it an edge.
However, it should be remembered that all the vaccines available offer good protective odds of reducing symptomatic infections, hospitalization and mortality against the Delta variant.
While COVID-19 vaccines have been made available free of cost at government institutions and hospitals, strategic deals have been signed, pricing of the vaccines is also an important factor under consideration.
Currently, Covishield, manufactured by Serum Institute of India (SII) is the cheapest vaccine under offer. Covaxin, manufactured by Bharat Biotech currently costs Rs. 1200, whereas Sputnik V is said to be priced around Rs. 950-1000.
Moderna’s mRNA vaccine, which has been granted nods for import, may be made available soon. However, while the pricing of the same hasn’t been publicly announced, it is expected that at private hospitals and centres, Moderna’s shot will be priced considerably higher than other vaccines. More details are awaited on the same.
Side-effects related to any COVID-19 vaccine are said to be reactogenic and resolve in a matter of 2-3 days. However, as has been seen, side-effects can also differ as per intensity, from vaccine to vaccine and can be a factor for consideration.
For example, as per experts, while Covishield prompts a higher antibody response with the first dose, the intensity of side-effects could be slightly higher than others. Covaxin on the other hand has been seen to lead to fewer side-effects, similar to that with Sputnik V.
The mild, reactogenic side-effects with most vaccines tend to be similar in nature, causing a low-grade fever, chills, fatigue, malaise, body pain, headache, or in some cases, nausea.
Moderna’s COVID-19 vaccine shot, too, offers reactogenic side-effects, which could be comparable to that of Covishield. It could also lead to unusual side-effects, such as the infamous ‘COVID arm’.
As for adverse reactions, the incidental cases have been on the rarer side. Having mentioned that, preliminary research suggests that Covishield and Moderna have a higher risk of adverse, or serious reactions, including blood clots and heart inflammation (myocarditis).
08/9 Which offers the highest level of immunity and protection?
The immunity granted by a COVID-19 vaccine is determined by the level of lasting antibodies it mounts. Currently, we do not have much clarity available on how long individual vaccines grant protection and immunity. However, recent studies have indicated that mRNA vaccines, such as the one offered by Moderna may be capable of offering longer immunity, which may remain in place for years to come, and hence may not even require a booster shot. The results are based on smaller studies and subject to more research. Nonetheless, it is nothing short of a ray of hope right now.
Researchers at the Oxford University, who also helmed the development of the Covishield vaccine have also recently highlighted how the administration of a booster shot, given 10 months from the first shot may help significantly boost antibody count and work to provide lasting immunity.
09/9 The bottom line
Wider availability will help people in India, as well as abroad make a more informed choice. The factors before choosing a vaccine can be dependent on a person’s age, pre-conditions and financial prospects. However, the takeaway message still remains to get the first vaccine available to you, and get inoculated as and when you can.
Delaying vaccination right now can be a risky choice to make while we remain worried about the emergence of a potentially scary third wave. The faster people get vaccinated, the better are the odds of protection and minimizing the dangers of future mutations and variants of concerns.
However, if you have concerning health conditions, or are immunocompromised, experts do advise people to take a suitable decision, weighing the pros and cons, talking to a doctor and choosing a vaccine appropriately, since they may need a vaccine which is more efficient and provides longer-lasting immunity. The same goes for someone who may be prone to allergies, or risks from COVID-19 vaccines.
What advantages do they grant against traditional vaccines?
Pfizer’s and Moderna’s mRNA vaccines were amongst the ones to be globally accepted and pushed into use. Like all vaccines, mRNA vaccines are administered to prompt a durable immune response, which is achieved via injection of two doses. Compared to traditional vaccines, mRNA vaccines help generate a stronger type of immunity, which would also be more effective against the pathogen, since they work to stimulate the immune system to not just produce antibodies, but also generate immune cells which attack the virus doubly.
The efficacy and effectiveness of the mRNA vaccines has also been something experts feel is much higher than other vaccines. While traditional vaccines have their own set of benefits and pros, clinical studies and evaluations have proven that mRNA vaccines, such as the ones offered by Pfizer and Moderna are also much more effective against mutant strains of coronavirus and create a tolerable immune response.
Many experts also feel that the use of mRNA technology also helps developers to efficiently mimic many variants, modify approaches as needed and launch fights against difficult variants. As per scientists, multiple mRNAs can be encoded in a single vaccine, which could permit them to target many antigens at once, which is something traditional vaccines cannot.
Despite carrying higher costs, mRNA vaccine development can also optimize production costs and timelines, helping speed up product development and scalability.