With more than 260 million cases and 5.2 million deaths due to Covid-19 worldwide as we enter the third year of the pandemic, it is clear that the battle is far from over. Almost all vaccines that are based on the initial Wuhan virus genome have held on to their promise of greatly reducing the risk of severe disease, hospitalisation, and death due to Covid, including the more infectious Delta, which now accounts for over 99% of the pandemic worldwide. But the recent, fierce fourth wave in European countries, more than two-thirds of whose populations are fully vaccinated, and a surge of infections in the US, have sent alarm bells ringing around the world.
It is an unfortunate fact that many rich countries have more vaccines in stock than they can consume. About 8 billion shots have been given, but an unacceptable gap remains between rich and poor countries. For example, vaccination coverage in many countries in Africa remains well below 10%.
For this, and several other reasons, Indonesia’s recent approval for emergency use of the first protein-based vaccine developed by Novavax is welcome news. Unlike the never-used-before platforms of the mRNA and viral vector vaccines, recombinant protein-based technology is time-tested and widely used for many viral diseases. Protein-based vaccines, while slow to develop, are more stable at higher temperatures, easy to scale up, highly cost-effective, safe, and efficacious. The Novavax vaccine showed more than 90% efficacy in a large phase 3 trial.
Several other protein-based vaccines are awaiting approval — including those from Biological E (India), Clover Biosciences (China), S K Biosciences (South Korea), and Sanofi/GSK (France/UK). Importantly, clinical trials of these vaccines were carried out when the Delta variant had already taken hold. Their superior safety profile should help address any remaining hesitancy issues. Besides the advantages of accessibility and affordability, these vaccines will be ideal candidates for mix-and-match strategies and booster shots. It is hoped that India will become a major supplier of protein-based vaccines from Biological E and Serum Institute of India.
The search for therapeutics started early in the pandemic. Several known antiviral, anti-infective, and anti-inflammatory agents were tested in clinical trials, but only a few, including remdesivir, were approved for use. However, these needed careful administration in hospitalised Covid-19 patients, and their limited supply, high cost, and moderate efficacy limited their impact.
The recent announcement of trial data of two separate antiviral drugs by Merck and Pfizer have raised hopes for easy-to-deliver therapeutic treatment of severe Covid. Both molnupiravir from Merck— which was approved for use in the UK on November 4 — and Paxlovid from Pfizer are pills based on small molecules that can be easily manufactured at scale. Moreover, these can be stored and dispensed at pharmacies, and taken orally at home.
Merck has said molnupiravir prevented severe disease and hospitalisation by about 50%; according to Pfizer, Paxlovid prevented hospitalisation by 89%, making it more efficacious than molnupiravir.
Molnupiravir targets a viral enzyme called RNA-dependent RNA polymerase, and introduces a large number of errors in the viral genome leading to severe hampering of replication. Paxlovid is a combination of two molecules, an antiviral and a drug called ritonavir, and acts by blocking the action of a viral enzyme that is crucial for converting viral proteins into their functional forms.
A five-day treatment course with molnupiravir requires 40 pills; that with Paxlovid requires 30, including 10 ritonavir pills. Both companies have claimed their drugs are safe, but some categories of patients like pregnant women may be excluded.
Many questions regarding the safety profile, efficacy in a range of populations, and development of resistance by the virus can only be answered after these drugs are rolled out at scale. The efficacy results of clinical trials will need to hold in the real-world situation. Indeed, Merck has said that the efficacy of molnupiravir may be lower than what was announced in October.
Both Merck and Pfizer have agreed to provide the drugs to poor countries at lower prices, and announced separate deals with Medicine Patent Pool, a UN-supported nonprofit, under which the drugs can be manufactured and sold for cheaper in poor and low-income countries. However, resource-rich countries such as the UK, US, and Australia have placed orders for sizeable numbers of these pills — many parts of the world may thus have to wait for a steady supply of these drugs, as has been the case with vaccines.
Also, since these oral pills need to be given early in the infection cycle, timely and quality testing infrastructure will need to be put in place, which may present a challenge for poorer countries. But after the many efficacious vaccines, the addition of oral pills as therapeutics will be another important scientific tool in controlling the pandemic.
The emergence of the highly infectious B.1.1.529 Omicron variant, containing a large number of mutations in the spike protein, has brought the virus back centre-stage. While it seems Omicron has spread fast in South Africa and neighbouring countries, its infectivity and ability to escape vaccine-induced immune responses are yet to be precisely ascertained. The panic response of some western countries to its emergence seems highly exaggerated. An earlier variant of concern, also first detected in South Africa in September 2020 (Beta), was shown to be highly infectious and with the ability to partially escape immune responses, but it did not spread widely.
The fact that most Covid vaccines have remained effective in breaking the link between infection and severe disease should nudge policymakers to be patient until the relevant scientific data are gathered. That said, we must remain cautious and well-prepared to deal with any situation due to Omicron. Viruses do not know international boundaries, and it is imperative that all scientific tools and interventions to control the pandemic are equally shared among the haves and have-nots. The best way to deal with Omicron is to go back to the basics with enhanced surveillance, rapid genome sequencing, increased testing and contact tracing, in addition to the Covid-appropriate behaviour of masking, physical distancing, and hygiene. Vaccines are our best bet to fight the virus, and therefore vaccination drives should continue with even greater vigour.
Virologist Dr Chauhan is Emeritus Scientist, International Centre for Genetic Engineering and Biotechnology, New Delhi
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