Of even more concern is the approval of the DNA vaccine from Cadila Healthcare in India for children 12-18 years old based on a small subset of data, without biodistribution studies and without evaluation of long-term safety aspects. in children.
The WHO also recently recommended a third dose for inactivated vaccines from China, which signifies an implicit acceptance of the low efficacy of Chinese vaccines.
Par KV Balasubramaniam
Idea in brief
The rapid response in the development of vaccines to combat the Covid pandemic has led to the approval of sub-optimal vaccines. While these vaccines may have helped bring the pandemic under control, they still fall short of the criteria for the safety and efficacy of a good vaccine. It is time to reset the benchmarks so that the fight against the transmission of the virus and the control of the disease are effectively achieved.
The story so far on Covid-19 vaccines
The Covid-19 pandemic is unprecedented in human history. As it ravaged planet Earth, it left in its wake significant loss of life, inflicted enormous morbidity and unbalanced the global economy, and with it the livelihoods of people. It was a crisis of incalculable dimensions.
Even as the medical community began to grapple with the new pandemic, the pharmaceutical industry rushed to find solutions to limit the damage and find more permanent solutions to the viral infection. The vaccine industry, which had some experience with previous outbreaks of SARS and MERS, was quick to come up with candidate vaccines against Covid-19. Western governments and multilateral agencies have invested huge amounts of resources. The light at the end of the tunnel appeared and the vaccine industry was able to come up with reasonable vaccine solutions. The speed of vaccine development and emergency mode approvals by regulators was unprecedented.
There are approximately six different vaccines that are currently approved internationally for emergency use – mRNA vaccines from Moderna and Pfizer / BioNtech, live vector vaccines from Astra Zeneca and Johnson & Johnson Janssen, and inactivated vaccines from Sinopharm and Sinovac. In addition, four vaccines are awaiting international approvals – the live vector vaccine from the Gamaleya Institute, the inactivated vaccine from Bharat Biotech, the subunit vaccine from Novovax and the DNA vaccine from Cadila Heathcare.
With the increasing use of these vaccines, several safety concerns have started to make headlines. For example, mRNA vaccines are said to cause myocarditis and, as a result, have been suspended in some Scandinavian countries, which are paying more attention to safety aspects. Likewise, Astra Zeneca’s live vector vaccine faces problems with brain clots and has been withdrawn from use for people under the age of 40 in some European countries.
Moreover, what is of concern is the relatively low level of efficacy of the vaccines. To compound this problem, the Delta strain has made vaccines even less effective. The drop in efficiency is uniform across all technology platforms. This even led Pfizer to claim high initial efficacy for its mRNA vaccine, now calling for booster doses for the entire population.
The WHO also recently recommended a third dose for inactivated vaccines from China, which signifies an implicit acceptance of the low efficacy of Chinese vaccines. Regarding the inactivated Indian vaccine – Covaxin, it appears that the WHO is still not convinced of the robustness of the clinical trials and the efficacy results, as it has repeatedly asked the company for more data.
The other troublesome issue is the general position that vaccines, although of low efficacy, have been effective against serious illnesses and have reduced hospitalizations for those vaccinated who become infected again. It must be argued that in the first place, vaccines should not cause the virus to reenter the stage, because a good vaccine with high immunity, and sterilizing immunity, would avoid this unfortunate situation. Sterilizing immunity is conferred when the vaccine can completely block the virus upon subsequent infection. This is important to stop the transmission of the virus and achieve more effective herd immunity.
Of even more concern is the approval of the DNA vaccine from Cadila Healthcare in India for children 12-18 years old based on a small subset of data, without biodistribution studies and without evaluation of long-term safety aspects. in children. DNA vaccines are known to interfere with the host genome with the threat of development of oncogenes, which is a serious problem. Advocating the use of a vaccine in children from a new technological platform without longitudinal studies is risky.
In addition, what is still not understood is the fact that the viral vector vaccine may not be effective in subsequent doses such as in boosters due to the resistance of the antibodies to the vector itself used in the vaccines, which makes them less effective. Given that India is relying heavily on the vector vaccine – Covishield, this raises concerns about the long-term usefulness of the vaccination campaign that relies on this vaccine.
Amid all this, the expectation that a vaccine should confer long-term immunity has all too conveniently been ignored. On the other hand, the refrain of vaccine suppliers has been on the need for boosters!
Disadvantages of First Mover vaccines
These worrying developments are a direct result of the rush to develop vaccines and the rush of regulators, pushed by governments desperate to grant emergency approvals. This was to ensure that vaccination could be carried out to achieve progressive herd immunity for the susceptible population and, therefore, that economic activity could be put back on track. The vaccines developed are not among the best vaccines you need to have. They represent at best a rapid response to an impending pandemic.
Now that many countries have achieved reasonable levels of immunization of their populations and the fury of the pandemic has dramatically reduced, it is time to demand that better vaccines be available. However, vaccine manufacturers who had the first-mover advantage seem to persist with their vaccines. Added to this is the reluctance of governments and even the WHO to prescribe new benchmarks for the efficacy and safety of vaccines. We can say that there could be a comfort with the status quo.
If the downsides are overlooked for too long, there will be a lot of price to pay due to the dire consequences of using relatively dangerous and ineffective vaccines, some of which are becoming too obvious now.
Need for safer and more effective Covid-19 vaccines
In the field of vaccines, it is a well accepted doctrine that a vaccine must first and foremost be a safe vaccine. Safety is not reflected only in the low level of adverse events immediately after vaccination. This is more reflected in the way the vaccine does not cause any unwanted long-term medical consequences. This is more important for children because the negative impact can have debilitating consequences over the course of their lives. It is no less important in vulnerable sections, such as the immunocompromised and elderly population, due to the high costs associated with disability. Therefore, vaccine safety is a primary consideration.
Only after satisfying the safety considerations are the efficiency considerations worth considering, as good efficiency without adequate safety can create more problems than it solves. Safety is evident in the technology platform chosen for the vaccine, while efficacy is an aspect that can be achieved through appropriate application of the technology and in the construction of the vaccine. For example, inactivated vaccines are considered safe and their efficacy can be improved by proper formulation with good adjuvants.
Therefore, now is the time to redefine the benchmarks for a good vaccine and the choices governments make in using vaccines for immunization campaigns. The key benchmark is vaccine safety, as the vaccine should be very safe in all age groups and in healthy and sick populations. On the efficiency parameter, the reference must be set with a stipulated efficiency greater than 90%. It is also important to look at the period of immunity conferred by the vaccine. The expectation is that the vaccine should confer robust and long-term immunity, not in months but in years.
Good vaccines on the horizon
A few good vaccines have emerged on the development horizon. Among them are subunit protein vaccines based on recombinant technology. It is a well known fact that recombinant vaccines are generally safe since what is injected as an antigen is a protein. A recombinant vaccine formulated with good adjuvants can confer good neutralizing and long-lasting immunity. Likewise, an inactivated vaccine is also considered safe and can confer good immunity with the right choice of adjuvant. 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. No wonder the large multinational vaccine companies – Sanofi and GSK, are jointly developing a subunit vaccine against Covid-19. Likewise, Covaxin (from Bharat Biotech) as an inactivated vaccine may also be safe. However, the problem with the inactivated vaccine is the higher manufacturing cost and the difficulties of large-scale manufacturing.
It is relevant to note that the subunit and inactivated vaccines can be used safely in children. As vaccination coverage evolves to cover children, it would be advisable to choose only these subunit or inactivated vaccines rather than mRNA, live vector or DNA vaccines. Most countries are on the verge of vaccinating children, and they would do well to redefine the settings for the safety and efficacy of Covid-19 vaccines so that the world as a whole gets a better vaccine to fight the pandemic.
When it comes to the proper choices regarding Covid-19 vaccines, safety is of paramount importance. As the Covid pandemic recedes and a large portion of the world’s population is still vaccinated, especially children under the age of 18, the need to reset the safety and efficacy bar of Covid-19 vaccines is taking a long time of importance. The world now needs safer and more effective Covid-19 vaccines. It’s time to act.
(The author is Ph.D, Life Sciences Consultant and Former MD, Indian Immunologicals Ltd. Opinions expressed are personal and do not reflect the official position or policy of Financial Express Online.)
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