Source : 'Scrip Intelligence'
In a world struggling for sufficient supplies of COVID-19 vaccines, South Africa refused to use one million doses of AstraZeneca PLC/University of Oxford partner Serum Institute of India Pvt. Ltd.’s vaccine, instead donating the lot to the African Union (AU). Another 500,000 doses are due to arrive in South Africa over the next few weeks and their fate is not yet clear.
The decision followed a study by the Vaccines and Infectious Diseases Analytics Research Unit of the University of the Witwatersrand in South Africa that showed a two-dose regimen of AZD1222 provides minimal protection against mild to moderate COVID-19 infection from the B.1.351/501.V2 strain of SARS-CoV-2m which has caused the majority of COVID-19 cases in the country of late. ()
Vaccinating with an option that could result in better outcomes is an obvious move and the South African government has decided to go ahead with Johnson & Johnson's single-dose vaccine, which studies have shown is 57% effective against mild disease from the B.1.351 strain. Immunization will begin in the form of an “implementation study”.
At the same time, South Africa reportedly paid $5.25 per dose to Serum Institute, and as the South African study gave no information on whether AZD1222 prevented serious cases of the disease, hospitalization or deaths, some health experts are not entirely convinced of the wisdom of the act.
Some sections of Indian media reported that South Africa had asked Serum Institute to take back the unused doses. However, during a state of the nation address debate in South Africa, the country’s health minister, Dr Zweli Mkhize, denied returning the vaccine to India, adding that the doses have an expiry date of 30 April. The AU will now distribute them to members who have already expressed interest in acquiring the stock, the minister said. Serum Institute did not comment when contacted by Scrip.
While this could prove to be a one-off, the incident also begs the question of whether newer vaccine strains will upend painstakingly negotiated supply deals in the future for vaccines, like that of AstraZeneca, that are shown to be less effective against them.
Several high-income countries like the US, UK, Canada and others from Europe have signed advance purchase agreements with multiple COVID-19 vaccine makers. Given that immunization programs in some, including India, are already underway, companies are under pressure to ensure timely manufacture and supply of such doses.
However, the situation also puts manufacturers at risk given that vaccines have a limited shelf life and in case of returns due to efficacy concerns, they will suffer financial losses, with revenue projections made by analysts going out the window.
In some cases, like that of Pfizer Inc./BioNTech SE's mRNA vaccine Comirnaty, over 90% efficacy against the original strain and a reasonable efficacy against B.1.351 and the UK variant B.1.1.7 mean that this can continue to be used, at least for now.
Researchers from the Aaron Diamond AIDS Research Center at Columbia University in the US found that, in the laboratory, Comirnaty was 6.5-fold and Moderna, Inc.’s vaccine 8.6-fold less effective against the strain. A later, real-world study by William James, professor of virology at the University of Oxford and his colleagues showed that in over 90% of cases, two doses of the Pfizer vaccine would be able to protect from infection by the South African strain and the UK strain, as well as the original strain of the virus.
COVID-19 vaccines made by J&J and Novavax, Inc. also offer protection against the South African strain. However, against mild disease, Novavax’s candidate was only 49% effective. Most vaccines, however, continue to offer immunogenicity against the B.1.1.7 variant, which spreads faster than the original SARS-CoV-2 virus. () ()
“There are many moving parts in this story. What happens to deals already negotiated with any of these companies if their vaccines fail to work against mutant strains depends on the specifics of the contracts. Clauses can be built in for vaccines to meet certain pre-determined parameters. But when there is a clamor for immunizing your population at the earliest and a supply shortage, vaccine companies will obviously have an upper hand in negotiations,” said one industry expert.
Nevertheless, efficacy against a higher number of strains will tilt the balance in favor of such vaccines, he added.
While AstraZeneca and the University of Oxford are working to produce a second generation of their vaccine adapted to target new variants of the coronavirus, the World Health Organization (WHO) granted emergency authorization to two versions of the vaccine on 15 February.
The first is one produced by Serum Institute under the brand name Covishield and the other is being manufactured in South Korea by SK Bioscience. () ()
Serum Institute has already supplied Covishield to multiple countries through privately negotiated deals and as donations by the Indian government. While the WHO approval is comforting, being faced with the ugly prospect of product returns is an unknown if the South African variant becomes rampant in more countries.
In India, the Indian Council of Medical Research has so far confirmed only four cases of the South African variant, detected in fliers who had returned from South Africa, Angola and Tanzania. However, it’s only a matter of time before the known variants become more widespread across the world and newer mutant strains are found, given that a still small percentage of the world’s population has been vaccinated so far.
Meanwhile, companies including Serum and SK Bioscience have committed to supply doses of the AstraZeneca and Novavax vaccines to the COVAX facility and the United Nations International Children's Emergency Fund (UNICEF). Pfizer/BioNTech have also entered a supply deal with UNICEF for Comirnaty.
At $3 a dose for low- and middle-income countries, the AZ and Novavax vaccines would be preferred for vaccinations in these areas. Besides, higher availability implies that the WHO might immunize populations wherever it can with these vaccines before Pfizer makes supplies available.
The WHO has continually underscored the importance of vaccinating as many people as possible at the earliest opportunity and even if the first dose provides a lower immune response, it always has the option of boosting with another vaccine with higher efficacy later, though the implications of combining vaccines are not yet known.
As the situation evolves and many more vaccines get approved, it will be interesting to watch who gains and who doesn’t.
By Vibha Ravi