Of more concern is the approval of Cadila Healthcare’s DNA vaccine in India for children aged 12-18 years based on a small subset of data, without biodistribution studies and without evaluating the long-term safety aspects in children.
By KV Balasubramaniam
idea in brief
The rapid response in developing vaccines to tackle the Covid epidemic has led to the approval of sub-optimal vaccines. While these vaccines may have helped tame the epidemic, they are still far from safety and effectiveness standards for a good vaccine. It is time to reset the standards so that transmission of the virus can be effectively combated and the disease controlled.
The story so far about the Covid-19 vaccines
The Covid-19 pandemic was unprecedented in human history. When it destroyed the planet, it left in its wake a huge loss of human life, inflicted great diseases with diseases, and threw the world economy, and with it people’s livelihoods. It was a crisis of unspeakable proportions.
Even as the medical community began to tackle the new pandemic, the pharmaceutical industry scrambled to find solutions to limit harm and find permanent solutions to viral infections. The vaccine industry, which has had some experience with previous SARS and MERS epidemics, has been quick to devise candidate vaccines against Covid-19. Western governments and multilateral agencies have engaged in huge expenditures of resources. The light appeared at the end of the tunnel and the vaccine industry was able to come up with reasonable vaccine solutions. The speed of vaccine development and emergency status approvals by regulators were unprecedented.
There are about six different vaccines currently approved for emergency use – the mRNA vaccines from Moderna and Pfizer/BioNtech, the live directed vaccines from Astra Zeneca and Johnson & Johnson Janssen and the inactivated vaccines from Sinopharm and Sinovac. In addition, four vaccines are awaiting international approval – a live vector vaccine from the Aesthetic Institute, an inactivated vaccine from Bharat Biotech, a subunit vaccine from Novovax and a DNA vaccine from Cadila Heathcare.
With the increasing use of these vaccines, many safety issues are beginning to arise. For example, mRNA vaccines have been reported to cause myocarditis and as a result have been put on hold in some Scandinavian countries, which are more careful about safety aspects. Likewise, the Astra Zeneca live vector vaccine has the potential for stroke problems and has been discontinued for people under the age of 40 in some European countries.
Also, of concern is the relatively low level of efficacy of vaccines. To exacerbate this problem, Delta strain has made vaccines less effective. The decrease in effectiveness is uniform across all technology platforms. This has led Pfizer to claim the initial high efficacy of its mRNA vaccine, which is now demanding booster doses for the entire population.
The World Health Organization also recently recommended a third dose of inactivated vaccines from China and this implies tacit acceptance of the low efficacy of Chinese vaccines. With regard to the inactivated Indian cofaxine vaccine, the World Health Organization still appears to be not convinced of the strength of clinical trials and efficacy results, repeatedly asking the company to provide more data.
Another troubling problem is the general attitude that vaccines, while less effective, were effective against serious diseases and reduced hospitalization for vaccinated individuals who became infected again. It must be said that in the first place, vaccines should not lead to the return of the virus to the stage of return because a good vaccine with high immunity, sterile immunity at that time, would avoid this unfortunate situation. Sterilization immunity is conferred when the vaccine is able to completely block the virus during subsequent infections. This is important to stop the transmission of the virus and to achieve more effective immunity to the herd.
Of more concern is the approval of Cadila Healthcare’s DNA vaccine in India for children aged 12-18 years based on a small subset of data, without biodistribution studies and without evaluating the long-term safety aspects in children. DNA vaccines are known to interfere with the host’s genome while threatening oncogene development and are a serious problem. Advocating for a pediatric vaccine from a new technology platform without longitudinal studies is risky.
Also, what is still not understood is the fact that the viral vector vaccine may not be as effective in later doses as in boosters due to resistance of the antibody to the vector used in the vaccines, making them less effective. Given that India is highly dependent on the targeted vaccine – CoviShield, this raises concerns about the long-term benefit of a vaccination campaign based on this vaccine.
Amid all this, the expectation that a vaccine should confer long-term immunity has been ignored. On the other hand, it was the reluctance of vaccine suppliers to need boosters!
Disadvantages of first mover vaccines
These worrying developments are a direct result of the rush to develop vaccines and the eagerness of regulators, driven by desperate governments to grant emergency approvals. This was to ensure that vaccination could be carried out to achieve progressive herd immunity to susceptible populations, and as a result, economic activity could be brought back to the rails. Upgraded vaccines are not among the best to have. It is at best a rapid response to a looming pandemic.
Now that many countries have achieved a reasonable level of vaccination for their populations and the anger of the epidemic has decreased significantly, it is time to demand better vaccines. However, it appears that vaccine companies that had a first mover advantage continue to use their vaccines. This is compounded by the reluctance of governments and even the World Health Organization to prescribe new standards for vaccine efficacy and safety. It can be said that there may be satisfaction with the status quo.
If the drawbacks are overlooked for too long, there will be a lot of price to pay due to the dire consequences of using unsafe and relatively ineffective vaccines, some of which are now very clear.
The need for safer and more effective Covid-19 vaccines
In the field of vaccines, it is a well-accepted principle that a vaccine should be, first and foremost, a safe vaccine. Safety is not only reflected in the low level of adverse events immediately after vaccination. This is further reflected in how the vaccine did not cause any long-term adverse medical downfall. This is even more important for children because negative effects can have devastating consequences in their lives. It is just as important in vulnerable sections, such as the immunocompromised population and the elderly, due to the high costs associated with disability. Therefore, the safety of vaccines is the first consideration.
Efficacy considerations deserve attention only after safety considerations have been met, since good efficacy without sufficient safety can create more problems than they solve. Safety is demonstrated in the technological platform chosen for the vaccine, while efficacy is an aspect that can be achieved through appropriate application of technology and in the formulation of the vaccine. For example, inactivated vaccines are safe, and their efficacy can be enhanced by appropriate formulation with good adjuvants.
So, now is the time to redefine the standards for a good vaccine and the choices governments make in the use of vaccines in vaccination campaigns. The main criterion is the safety of the vaccine, and that the vaccine must be very safe across age groups and across healthy and sick populations. With regard to the potency factor, the standard should be set with the stated efficacy above 90%. It is also important to look at the period of immunity conferred by the vaccine. The expectation is that the vaccine should confer strong and long-lasting immunity, not in months but in years.
Good vaccines are on the horizon
Some good vaccines are on the horizon for development. Among them are subprotein vaccines based on recombinant technology. It is a known fact that recombinant vaccines are generally safe because what is injected as an antigen is protein. A recombinant vaccine made with good adjuvants can give good long-lasting and neutral immunity. Similarly, inactivated vaccine is also safe and can confer good immunity with good choice of adjuvants. In the list of these vaccines are Novovax (Covovax by Serum Institute in India), RelCovax (by Reliance Life Sciences), and Corbevax (by Biological E) as subunit vaccines. Not surprisingly, seasoned multinational vaccine companies – Sanofi and GSK, are developing a subunit vaccine against Covid-19. Likewise, Covaxin (by Bharat Biotech) as an inactivated vaccine can also be safe. However, the problem with an inactivated vaccine is the high cost of manufacturing and the difficulties of manufacturing on a large scale.
It is noteworthy that both subunit and inactivated vaccines are safe for use in children. As vaccination coverage progresses to cover children, it would be appropriate to choose only these subunits or inactivated vaccines rather than mRNA, live vector, or nucleic acid vaccines. Most countries are on the verge of vaccinating children, and they would do well to redefine standards of safety and efficacy for Covid-19 vaccines so that the whole world has a better vaccine to tackle the pandemic.
In terms of making appropriate choices regarding Covid-19 vaccines, safety is of paramount importance. With the Covid epidemic receding and much of the world’s population still being vaccinated, especially children under 18, the need to reset the bar for safety and efficacy for Covid-19 vaccines is of great importance. The world now needs safer and more effective vaccines for Covid-19. It’s time to act!
(The author is a Ph.D., life sciences consultant, and former physician, Indian Immunologicals Ltd. The opinions expressed are personal and do not reflect the official position or policy of Financial Express Online.)
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