Covid-19 vaccines – Time to reset the impact bar

Even more concerning is the approval of the DNA vaccine of Cadila Healthcare in India for children in the 12-18 age group based on a small subset of data, without biodistribution studies and without evaluation of long-term safety aspects in children.

October 15, 2021 5:54 PM
WHO has also recently recommended a third dose for the inactivated vaccines from China and this means an implicit acceptance of the low efficacy of the Chinese vaccines.

By K V Balasubramaniam

Idea in Brief

The rapid response in developing vaccines to tackle the Covid pandemic has led to approval of sub-optimal vaccines. While these vaccines may have helped tame the pandemic, they still fall way short of the benchmarks of safety and efficacy for a good vaccine. It is time to reset the benchmarks so that the combating transmission of the virus and control of the disease is effectively achieved.

The Story So far on Covid-19 Vaccines

The Covid-19 pandemic has been unprecedented in human history. As it ravaged across planet earth, it left in its wake extensive loss of human lives, inflicted huge morbidity, and threw out of gear the world economy, and with it the livelihoods of people. It was crisis of untold dimensions.

Even as the medical community began to tackle the new pandemic, the pharmaceutical industry scrambled to find solutions to limit the damage and find more permanent solutions to the viral infection. The vaccine industry, which had some experience with the previous SARS and MERS epidemics was quick to come up with vaccine candidates against Covid-19. Western governments and multilateral agencies pitched in with huge resource outlays. The light at the end of the tunnel emerged and the vaccine industry was able to come up with reasonable vaccine solutions. The speed of vaccine development and approvals on emergency mode by regulators was unprecedented.

There are about six different vaccines which are presently internationally approved for emergency use – the mRNA vaccines of Moderna and Pfizer/BioNtech, the live vectored vaccines of Astra Zeneca and Johnson & Johnson Janssen and the inactivated vaccines of Sinopharm and Sinovac. In addition, four vaccines await international approvals – the live vectored vaccine of Gamaleya Institute, the inactivated vaccine of Bharat Biotech, the sub-unit vaccine of Novovax and the DNA vaccine of Cadila Heathcare.

Worrying Developments

With growing use of these vaccines, several safety issues have started making news. For example, the mRNA vaccines are reported to cause myocarditis and as a result have been put on hold in some Scandinavian countries, who are more careful about the safety aspects. Likewise, the live vectored vaccine of Astra Zeneca faces issues of brain clots and has been taken off use for people below 40 years in some European countries.

Also, what is of concern is the relative low level of efficacy of the vaccines. To compound this problem, the Delta strain has made the vaccines even less efficacious. The drop in efficacy is uniformly across all technology platforms. This has led to even Pfizer with initial high efficacy claim for its mRNA vaccine, now clamouring for booster doses for the entire population.

WHO has also recently recommended a third dose for the inactivated vaccines from China and this means an implicit acceptance of the low efficacy of the Chinese vaccines. As regards the Indian inactivated vaccine – Covaxin, it appears that WHO is still not convinced about the robustness of the clinical trials and the efficacy results, as it has repeatedly asked the company for more data.

The other discomforting issue is the general position that the vaccines, although of low efficacy, have been effective against serious disease and reduced hospitalisation for vaccinated individuals contracting the infection again. It must be argued that in the first place, the vaccines should not result in the virus staging re-entry since a good vaccine with high immunity, and a sterilising immunity at that, would avoid this unfortunate situation. A sterilising immunity is conferred when the vaccine can completely block the virus during subsequent infection. This is important to stop transmission of the virus and to achieve more effective herd immunity.

Even more concerning is the approval of the DNA vaccine of Cadila Healthcare in India for children in the 12-18 age group 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 threat of oncogene development which is a serious issue. To advocate use of a vaccine in children 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 effective in the subsequent doses as in boosters due to antibody resistance to the very vector used in the vaccines, making them less effective. Considering that India is banking heavily on the vectored vaccine – Covishield, this does pose concerns about the long-term usefulness of the vaccination drive which banks on this vaccine.

Amidst all this, the expectation that a vaccine must 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 worrisome developments are directly the result of the rush to develop vaccines and the eagerness of regulators, pushed by desperate governments to grant emergency approvals. This was to ensure that vaccination can be carried out to achieve progressive herd immunity for the susceptible population and as a result, economic activity can be put back on rails. The vaccines developed are not among the best vaccines that must be had. They at best represent a quick response to a looming pandemic.

Now that many countries have achieved a reasonable level of vaccination of their population and the pandemic’s fury has greatly reduced, it is time to call for better vaccines to be available. However, the vaccine companies which had the first mover advantage seem to be persisting with their vaccines. Compounding this is the reluctance of governments and even WHO to prescribe new benchmarks for vaccine efficacy and safety. It can be said that there could possibly be comfort with the status quo.

If the disadvantages are overlooked for too long, there will be much price to be paid due to the dire consequences of using relatively unsafe and ineffective vaccines, some of which are getting to be all too apparent now.

Need for Safe and More Effective Covid-19 Vaccines

In the vaccine field, it is a well-accepted doctrine that a vaccine must first and foremost be a safe vaccine. Safety is not reflected just in the low level of adverse events immediately following vaccination. It is reflected more in how the vaccine does not cause any long term adverse medical fall out. This is more important for children since the adverse impact can have debilitating consequences in their lifetime. It is no less important in the vulnerable sections, such as the immunocompromised and aged population, due to the high disability related costs. Therefore, safety in vaccines is a paramount consideration.

It is only after safety considerations are met that the efficacy considerations merit attention, since good efficacy without adequate safety can create more problems than they solve. Safety is manifest in the technology platform chosen for the vaccine, whereas efficacy is an aspect which can be achieved by proper application of the technology and in the vaccine construct. For example, inactivated vaccines are considered safe, and their efficacy can be enhanced by proper formulation with good adjuvants.

Therefore, it is now time to redefine the benchmarks for a good vaccine and the choices that governments make in the use of the vaccines for the vaccination campaigns. The key benchmark is of the safety of the vaccine, that the vaccine must be very safe across age groups and across the healthy and sick populations. On the efficacy parameter, the benchmark must be set with efficacy stipulated to be above 90%. It is also important to look at the immunity period conferred by the vaccine. The expectation being that the vaccine must 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 the sub-unit protein vaccines based on recombinant technology. It is a well-known fact that recombinant vaccines are generally safe since what is injected as the antigen is a protein. A recombinant vaccine formulated with good adjuvants can confer good neutralising and long-lasting immunity. Likewise, an inactivated vaccine is also considered safe and can confer good immunity with a good choice of adjuvant. In the list of such vaccines are Novovax (Covovax by Serum Institute in India), RelCovax (by Reliance Life Sciences) and Corbevax (by Biological E) as sub-unit vaccines. Not surprising that the seasoned multinational vaccine majors – Sanofi and GSK, are jointly developing a subunit vaccine against Covid-19. Likewise, Covaxin (by Bharat Biotech) as an inactivated vaccine can also be safe. However, the issue with inactivated vaccine is the higher cost of manufacture and difficulties with manufacturability at scale.

It is pertinent to note that both the sub-unit and inactivated vaccines are safe for use in children. With vaccination coverage advancing to cover children, it would be appropriate to choose only these subunit or inactivated vaccines rather than the mRNA, live vectored or DNA vaccines. Most countries are at the threshold of vaccinating children, and they would do well to redefine the safety and efficacy parameters of the Covid-19 vaccines so that the world at large gets better vaccine to tackle the pandemic.

Conclusion

In the matter of making appropriate choices regarding Covid-19 vaccines, safety is of paramount importance. With the Covid pandemic receding and much of the world population to be still vaccinated, especially children under 18 years, the need to reset the safety and efficacy bar for Covid-19 vaccines assumes much importance. The world now needs safer and more efficacious Covid-19 vaccines. The time to act is now.

(The author is Ph.D, Life Sciences Consultant and Former M.D, Indian Immunologicals Ltd. Views expressed are personal and do not reflect the official position or policy of the Financial Express Online.)

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