As COVID-19 deaths across the globe top 3 million, with more than 1 million in Europe alone, the global demand is increasing for mRNA vaccines, even as sponsors of adenovirus vaccines push back against ongoing safety concerns.

Last week, the World Health Organization’s (WHO) Regional Office for Europe reported that the confirmed COVID-19 death toll for the region had surpassed 1 million, with 1.6 million new cases being reported every week. More than 171 million doses of COVID-19 vaccines have been administered in the region, translating to nearly 13% of the European population receiving one dose and close to 6% completing both doses of the vaccines.

With hospitalization levels high throughout Europe (France is seeing its highest levels in a year) and several EU countries reporting that intensive care units have exceeded their capacity, the European Commission exercised its option to purchase an additional 100 million doses of the Pfizer Inc.-Biontech SE COVID-19 Comirnaty vaccine, bringing the total number of doses the companies will deliver to the EU to 600 million. That’s enough to cover two-thirds of the EU population, Sean Marett, Biontech’s chief business and chief commercial officer, said April 19.

Pfizer Chair and CEO Albert Bourla said the companies plan to deliver 250 million vaccine doses to the EU this quarter for a fourfold increase of the quantity delivered in the first quarter.

Europe isn’t the only region looking for ways to deal with a COVID-19 surge. WHO officials are tracking the spread of a variant, B1617, in India. First seen in two states in India late last year, the coronavirus variant is now responsible for an increasing proportion of COVID-19 cases across the country, and the variant was detected in the U.S. earlier this month.

B1617 has two specific mutations in its genome, the E484Q and the L452R. Those mutations may increase transmissibility and result in reduced neutralization, which could have an impact on the efficacy of vaccines and other countermeasures, the WHO’s Maria Van Kerkhove said at an April 16 press conference.

The WHO is working with India and other countries to increase sequencing to detect variants that could impact the continuing response to the pandemic, Van Kerkhove said.

Also on April 16, the Biden administration announced a U.S. investment of $1.7 billion, to be allocated through the CDC, to help states and other jurisdictions more effectively detect and track COVID-19 variants by scaling genomic sequencing efforts.

WHO tech transfer initiative

On the vaccine front, the WHO launched an initiative April 16 to establish a technology transfer hub to help low- and middle-income countries (LMICs) produce COVID-19 vaccines and scale up manufacturing to increase global access. The immediate focus will be on mRNA technologies, such as those used in the Moderna Inc. and Pfizer-Biontech vaccines, but the WHO said it could be expanded to other technologies in the future.

The initiative proposes a “hub-and-spoke model” to voluntarily transfer a comprehensive technology package and provide appropriate training to interested manufacturers. As the next step, the WHO is seeking small or middle-sized manufacturers of medical products in LMICs that could host a COVID-19 mRNA hub, assemble the technology up to good manufacturing practices-grade pilot lots for clinical trials and transfer the know-how and technology to existing or new manufacturers in LMICs so they can develop and produce the vaccines. The initiative also will depend on the owners of the technologies being willing to contribute their intellectual property through nonexclusive licenses. “Preference will be given to applicants who have already generated clinical data in humans, as such clinical data will contribute to accelerated approval in LMICs,” according to the WHO.

The WHO initiative comes as pressure mounts for U.S. President Joe Biden to get behind a proposed World Trade Organization waiver of IP rights for vaccines, therapies and devices being used in the pandemic. Last week, 10 U.S. senators, led by Bernie Sanders (I-Vt.) and Elizabeth Warren (D-Mass.), were the latest to call on Biden to support the temporary waiver proposed by India and South Africa.

The “waiver is essential to eliminating restrictions that currently prevent countries from manufacturing COVID-19 treatments, vaccines and testing supplies,” the senators said in an April 15 letter. They added that WHO efforts to meet the global demand have proved inadequate.

“Simply put, we must make vaccines, testing and treatments accessible everywhere if we are going to crush the virus anywhere,” the lawmakers told Biden.

What that letter and the WHO’s latest initiative ignore is that the access problem isn’t just IP rights and technology. The Serum Institute of India Pvt. Ltd., for instance, is looking to boost its manufacturing of licensed COVID-19 vaccines, but getting the necessary raw materials could be an obstacle. In an April 16 tweet to Biden, the institute’s CEO, Adar Poonawalla, said, “If we are to truly unite in beating this virus, on behalf of the vaccine industry outside the U.S., I humbly request you to lift the embargo of raw material exports out of the U.S. so that vaccine production can ramp up.”

Vaccine safety

Meanwhile, the debate about the safety of COVID-19 adenovirus vaccines made by Johnson & Johnson (J&J) and Astrazeneca plc continues. Australia’s Therapeutic Goods Administration (TGA) reported April 16 a third case of thrombosis with thrombocytopenia (TTS) that is “likely linked to vaccine.” The case involved a 48-year-old woman with underlying health conditions who died last week after she developed blood clots four days following vaccination with Astrazeneca’s vaccine. Some tests are still pending, but “in the absence of an alternative cause for the clinical syndrome, [a panel of independent expert advisers] believed that a causative link to vaccination should be assumed at this time,” the TGA said.

With at least 885,000 doses of Astrazeneca’s vaccine administered in Australia to date, three cases of TTS equates to a frequency of one in 295,000, the TGA said.

Following six similar reports of blood clots with thrombocytopenia, use of J&J’s vaccine was paused last week in the U.S. The pause was continued when the CDC’s Advisory Committee on Immunization Practices declined to make a recommendation on a path forward April 14, despite the impact the hold could have on some populations. The pause could be lifted after the committee holds a second emergency meeting April 23 to once again discuss the risk-benefit profile of the J&J vaccine.

In a letter to the editor published April 16 in The New England Journal of Medicine, J&J pointed out that with more than 7.2 million doses of its vaccine being administered globally as of April 14, only six blood clotting incidents have been reported – a rate of less than one per 1 million vaccinations, which is within the range of published background incidence. “At this time, evidence is insufficient to establish a causal relationship between these events and [J&J’s] vaccine,” according to the letter.

Countering suggestions that COVID-19 vaccines that use an adenoviral vector platform may be related to the occurrence of the rare blood clots, J&J pointed out the different phylogenetic and biologic characteristics of its vaccine vs. the Astrazeneca vaccine.

Russia’s Gamaleya National Center of Epidemiology and Microbiology made the same argument last week when it differentiated its adenovirus vaccine, Sputnik V, from those of Astrazeneca and J&J. However, Russian officials appeared to be taking a different tack a few days later when they tweeted about an Oxford University study that they claimed showed “the risk of portal vein thrombosis appears to be 30 times higher with mRNA vaccines (Pfizer and Moderna) than with Astrazeneca’s.”

Actually, Oxford’s retrospective analysis of the electronic health care records of more than 500,000 COVID-19 patients found that infection with SARS-CoV-2 carries “a significantly and substantially” greater risk of cerebral venous thrombosis (CVT) than does either one of the two approved mRNA COVID-19 vaccines.

But the concern with the J&J and Astrazeneca vaccines is CVT with thrombocytopenia, which is a low platelet level that makes it more challenging to treat the blood clots. Experts speaking at last week’s ACIP meeting noted that no such cases have been observed with the mRNA vaccines, which have had 182 million doses administered.

In other news, the Russian Direct Investment Fund and Hualan Biological Bacterin Inc., a subsidiary of China’s Hualan Biological Engineering Inc., announced April 19 an agreement for the production of more than 100 million doses per year of Sputnik V in China. The agreement follows a recent acknowledgment from the director of China’s Centers for Disease Control that coronavirus vaccines developed in China “don’t have very high protection rates.”

Based on an analysis of data on the COVID-19 infection rate among people in Russia who have completed the Sputnik V dosage, Russian health officials claimed April 19 that Sputnik V has demonstrated efficacy of 97.6%. Sputnik V has been approved in more than 60 countries, but it has yet to be approved by regulatory agencies with standards akin to those of the U.S. FDA.