We have learned many lessons from COVID-19, but how to get vaccines to low- and middle-income countries effectively isn’t one of them.
Pandemic threats stirs complicated reactions for many. The economic and personal repercussions of COVID-19 are still with us, like the disease itself. It is surely disappointing — not least for those in biotech — that none of the lessons learned from COVID are fully implemented even for one potential future pandemic cause. The World Health Organization (WHO) and the Coalition for Epidemic Preparedness Innovations (CEPI) have lists of possible threats. This season, influenza (H5N1) ‘avian flu’ and mpox are on the list, among 10 or 20 others. The infrastructure for action is there. Endeavors such as the 100 Days Mission set a framework for rapid and effective diagnostic, vaccine and drug responses to emerging threats. Objectively, the world is better prepared for avian flu than for mpox and yet, measurably, it is not even close.
One lesson from COVID-19 is the importance of tracking disease progression in preventing spread. For H5N1, global surveillance systems overseen by WHO have tracked the evolution of isolates of H5N1 in animal populations since 2003. The current spreading variants began making rounds in 2020. Reports of H5N1-infected cattle herds in Texas and Kansas in March 2024 set off louder alarm bells, since the virus had not previously been detected in cows. Within just days, the United States notified WHO of the first human case, and by April it had 13 reported human cases, all of which could be traced to people with direct interactions with infected cattle or poultry. Early reporting brought immediacy and captured attention: cows and cowherds were affected, the disease was close to houses in the US, and it was not a one-off. In early August, the US Centers for Disease Control and Prevention (CDC) increased slightly its estimate that H5N1 might cause another human pandemic.
Understanding of molecular characteristics helped to further focus the surveillance effort in H5N1. Human–human respiratory transmission would likely require changes in both the viral replication machinery and viral surface proteins, characteristics likely to be associated with increased pathogenicity. The CDC is looking for those additional mutations that may make the virus more dangerous to humans. PB2, a viral polymerase subunit, is of particular concern. The usual version of the polymerase interacts poorly with human or mammalian replication machinery, but several PB2 mutations have been detected in H5N1 strains in mammals since 2020 that enable mammalian transmission. Even with this focused approach, tracking the virus is difficult. This is partly because only about 200 people have been tested. It is also partly because most testing is left up to farmers and so is performed only when required — if cattle are moved between states, for instance, or when cows are visibly ill. There has been no effort at wider preemptive screening or testing asymptomatic at-risk workers.
These are clear gaps in the surveillance and reporting system in H5N1, where knowledge of the potential mechanisms of evolution are relative high. For mpox, the gaps in surveillance are much bigger. The systems are uncoordinated and relatively unstructured, and knowledge of mpox biology is more fragmentary. But it is clear that mpox is back, and that it has changed.
In August 2024, WHO declared mpox a public health emergency of international concern with a new strain infecting at least 17,000 people in Africa and causing over 500 deaths in the Democratic Republic of the Congo alone this year. For comparison, only there were over 100,000 reported cased in the 2022–2023 mpox outbreak but only 225 deaths. Cases have been confirmed in neighboring African countries and in travelers from Africa to Europe and Thailand.
The world is not entirely unprepared for potential pandemics. There are vaccines, for instance, for both mpox and influenza H5N1. Inactivated H5N1 vaccines are available immediately if human–human transmission emerges. The European Commission procured 700,000 doses in June, with an option for 40 million more if needed. EU member Finland began vaccinating at-risk farm and laboratory workers in June. The US is vaccinating farm workers against seasonal human flu, a strategy designed to avoid dual infections that could accelerate human transmissibility. mRNA vaccination — the fast-track, flexible solution that helped resolve COVID-19 in developed nations — has advanced, too. In July, GlaxoSmithKline (GSK) bid $430 million up front to develop and manufacture CureVac’s mRNA vaccines, including its phase 1/2 mRNA vaccine for bird flu, and the US Department of Health and Human Services recently provided Moderna with $176 million for its modified mRNA phase 3 candidate.
For mpox, the vaccines pipeline is more pinched but not quite monopolistic. Bavarian Nordic’s Jynneos, a live attenuated vaccinia strain, is approved in the US and Europe, and KM Biologics’ LC16 is approved in Japan. BioNTech, backed by CEPI, has a phase 1/2 candidate in trials. Three issues still stand out: cost, timing and a mismatch in distribution. The European Union, the United States and Bavarian Nordic combined pledged 255,000 vaccine doses in the short term, a figure not even close to the 10 million doses the director-general of the Africa Centres for Disease Control and Prevention (Africa CDC) declared would be needed to control the mpox epidemic. Bavarian Nordic is working closely with Africa CDC to look at transferring manufacturing technology to African producers, but whether KM Biologics or BioNTech will take a similar outlicensing approach for their mpox products and candidates is not clear; neither is the fate of CureVac and GSK’s or Moderna’s candidates in influenza H5N1.
Three years on from COVID-19, companies seem as reluctant as ever to tune their commercial strategies to the needs of low- and middle-income countries (LMIC) to help in creating markets from erstwhile dependencies. Defensive stockpiling continues, vaccine prices remain high, and manufacturing is distant. The shift from a proprietorial attitude could have started as the last emergency receded, but it did not. It could start now, and if it does not, other routes may force manufacturers’ hands. In South America, WHO has launched a new initiative with Argentinian biosimilar and vaccines manufacturer Sinergium Biotech to accelerate the development and accessibility of an H5N1 mRNA vaccine. With COVAX (COVID-19 Vaccines Global Access) largely in tatters despite some good intentions, LMICs have no reason to trust that vaccines (or drugs or diagnostics) will ‘trickle down’ for pandemic emergencies. The question is not whether WHO manufacturing initiatives in Africa will occur, but when. The choice for innovative companies then becomes only be whether to hinder or to help.
The current responses to both bird flu and mpox are inadequate and characterize a world that promotes solutions compatible with financial goals. Lurching from one emergency to another is an option — but acting on multiple global health threats is better, even if it does requires more imagination and planning.
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