The total number of Covid-19 vaccine doses is approaching 7 billion. In a world with 7.9 billion people, that sounds like impressive coverage of the global population. But in reality, those doses are extremely unevenly distributed, creating a potentially dangerous worst-case pandemic scenario in which a failure to distribute vaccines in low- and middle-income countries creates conditions that encourage the evolution of viral variants, particularly variants that are resistant to vaccines and capable of driving devastating new waves of deaths, even in highly vaccinated nations.

According to a recent report from Doctors Without Borders, more than 60 percent of people in high-income countries (HIC) have received at least one dose of vaccine, while less than 3 percent of people in low-income countries (LIC) have received a shot. And even as health care workers and high-risk individuals remain unvaccinated in low-income countries, pharmaceutical companies are marketing extra doses in high-income countries.

According to the World Health Organization, even if all eligible people in the US, Canada, and eight European countries received third dose boosters, over 870 million vaccine doses will be left over, and quickly approaching their expiration dates.

As unused vaccine doses pile up, so does evidence that herd immunity through natural infection may not be an achievable goal for Covid-19. Early in the pandemic, epidemiologists predicted that once a certain percentage of the population had been infected–for example, 60 percent or 70 percent, the pandemic would naturally come to an end. Essentially, they believed it would burn itself out.

However, more than a year and a half into the pandemic, herd immunity has not been achieved in any country, in spite of very high levels of exposure, particularly in LICs where vaccination rates remain low. In fact, a recent analysis of excess death data from one LIC, Iran, predicted that in 11 of Iran’s 31 provinces, infection rates exceeded 100 percent of the population. The most likely explanation for that is that people are becoming infected again. That’s according to a new study from Oxford researchers Mahan Ghafari and Aris Katzourakis.

Iran had a late start to its vaccination program. At the end of July, only 3 percent of its population was vaccinated. The delay has been attributed to ineffective pandemic mitigation measures and conspiracy theories promoted by Iran’s Supreme Leader Ayatollah Ali Khamenei. This made Iran a good example of a country where extensive spread of the virus might have led to herd immunity.

“If this data is correct and our interpretation of it is correct, then these waves of infection are not giving the background population the kind of immunity that it needs to slow down the spread of the virus and subsequent waves of infection and death,” says Katzourakis. “It really shines a hard light on the need for not relying on this, and making sure that these countries do get the access to vaccines that they need. And unfortunately, on some occasions having to take other measures until that point. Otherwise, they’ll be seeing this wave after wave of death.”

This is consistent with previous studies showing significant rates of reinfection and pandemic waves overshooting the putative herd immunity threshold. For example, in October 2020, a study in The Lancet reported that 76 percent of the population of Manaus, Brazil had been infected with SARS-CoV-2, based on a survey of blood donors. Nonetheless, Manaus was subsequently crushed by a fresh surge of cases and deaths just two months later. The highly transmissible gamma variant was identified as the culprit behind that surge.

New laboratory evidence backs up what epidemiologists are seeing in the field, with separate studies finding a reinfection rate of 27 percent and a median time to reinfection with SARS-CoV-2 of just 16 months.

Even without evidence that the pandemic will never burn itself out through natural herd immunity, distributing vaccines to low- and middle-income countries seems like a no-brainer. It’s obvious the pandemic is not over until it’s over everywhere. That’s the idea behind COVAX, a global initiative led by Gavi, the Vaccine Alliance, and WHO. Launched in June 2020 with the support of the Bill and Melinda Gates Foundation, it coordinates 190 participating countries to distribute Covid-19 vaccines worldwide in a timely and equitable manner. COVAX has fallen far short of its goal to deliver two billion doses by the end of 2021. As of September, it had only delivered 230 million doses, and some of those went to high-income countries.

So what’s the hold up? Why are high-income countries hoarding millions of doses of vaccine while the virus rampages through unvaccinated low- and middle-income countries? It’s a dynamic between governments and pharmaceutical companies, says Doctors Without Borders.

“The hoarding is happening because from the beginning, high-income countries were making deals with manufacturers to ensure that they had enough supply of the vaccines, and high-income countries are holding on to these vaccine doses in the hopes of providing boosters, whereas the rest of the world hasn’t had the same kind of access to these vaccines,” says says Dr. Sharmila Shetty, Vaccines Medical Advisor for Doctors Without Borders, and one of the authors of the organization’s report, which charges the pharmaceutical industry with profiteering from the pandemic:

“Pharmaceutical companies are making huge profits from vaccines whose development was substantially paid for by taxpayers. BioNTech-Pfizer and Moderna estimate they will earn US$26 billion and $19.2 billion, respectively, in sales from COVID-19 vaccines in 2021. They have together secured over $60 billion in sales of the shots just for 2021 and 2022. Furthermore, BioNTech-Pfizer and Moderna recently raised their COVID-19 vaccine prices in the UK and EU.”

A recent editorial in theBMJ goes further, calling pharmaceutical profits from the pandemic a crime against humanity and a protection racket.

“Vaccine preventable deaths and illness are occurring across Africa, Asia, and Latin America at an unprecedented speed and scale. These continents are being outmanoeuvered by rich nations flexing their market power. Let us be clear what is causing these deaths: a free market, profit-driven enterprise on patent and intellectual property protection, combined with a lack of political will. Contrary to claims, it is possible to make enough vaccines for the world.”

Solutions proposed include urgent redistribution of excess doses by high-income countries as well as changes by manufacturers including removal of contractual barriers, technology transfer allowing their vaccines to be manufactured elsewhere, and assumption of liability for vaccine injuries, relieving low-income governments of that burden.

“Manufacturing is being held in a couple of hands and those are mostly in high-income countries right now,” says Shetty. She explains that DWB is asking for vaccine manufacturers, especially mRNA vaccine manufacturers, Moderna and Pfizer, to transfer their manufacturing capacity to other countries, especially in the African continent, so that they can be self-sufficient and create enough doses for themselves. That would also allow them to anticipate future global pandemics and respond using their own capacity rather than being reliant on charity. “The charity model really has not been working, especially not in the pandemic.”

According to Shetty, the consequences of failing to redistribute vaccine doses as quickly as possible are dire. “All viruses mutate. When you have non-immune populations, people who are susceptible to the virus, the more the virus circulates, the more it has a chance to mutate. The more it has a chance to mutate, the more it can mutate into these variants of concern,” says Shetty.

As Delta driven cases abate worldwide, public health experts are watching the Delta Plus variant closely. That variant, a sublineage of Delta, is not yet a “variant of concern.” It’s considered a “variant under investigation.” In the UK, which has one of the world’s best genomic surveillance programs for new variants, Delta Plus cases are on the rise, accounting for 6 percent of total cases, and there are signs that it may be more transmissible than Delta.

Not only would failing to vaccinate low and middle income countries fuel potentially endless cycles of new infection and emergence of new variants, it could lead to the emergence of a truly vaccine resistant variant. “The worst case scenario would be a variant developing that would evade the vaccine-induced immunity,” explains Shetty. Current vaccines remain highly effective against known variants, but if one emerged that could not be stopped with those vaccines, “All of the vaccines that we would have would no longer be effective and we’d have to scramble to develop new vaccines that would be targeted against that particular variant.”

Even if vaccine doses can be quickly and equitably distributed, even that might not be enough to stop the pandemic. That’s according to Deepti Gurdasani, a clinical epidemiologist with Queen Mary University of London, who recommends a “vaccine plus” approach. “Vaccines alone are not the answer, because the same waning of immunity that you see with natural infection, you also see with vaccines,” says Gurdasani. “And as new variants evolve, vaccines are less effective against them.” She lists upgrades in ventilation, remote work accommodations, and masks as some of those additional measures that are needed. “It has to be mitigations and vaccination.”

David Fisman, an epidemiologist with the University of Toronto, agrees with a vaccine-plus approach. “Vaccination alone may not be enough for a return to normalcy; light-touch interventions that reflect the aerosol nature of this disease…masks, HEPA cleaners, open windows, improved ventilation, will help a lot, as will smart and widespread use of rapid testing.”