As the uptake of the bivalent COVID-19 vaccine sputters and stalls—with just 8.5% of eligible Americans getting it, according to the Centers for Disease Control and Prevention—experts and researchers look to find ways to make inoculation against the ever-expanding roster of COVID-19 variants manageable.
They also search to find ways to coexist with other coronaviruses that will almost certainly be coming at us. As a subtitle in an article accompanying the release of one of two preprint studies dealing with vaccines that landed this week put it: “next threat not if but when.”
The research comes at a time when the Biden administration is looking to shift the costs of COVID-19 vaccines, tests and treatments to commercial health insurers.
One of the studies unveiled this week, from researchers with Columbia University and the University of Michigan and published on the website bioRxiv, focuses on what might be holding some individuals back from getting not only the bivalent shot, but any COVID-19 vaccine: Why get it if it doesn’t work?
BioRxiv is an open-access repository for preprint studies; its prominence rose during the fast-moving and mutating pandemic, because, often by the time peer-reviewed studies came out, the information and conclusions would be dated (e.g., studies that focused on the original COVID-19 strain as delta rampaged through the world).
The bivalent COVID-19 vaccine manufactured and sold specifically on the premise that it targets the BA.4 and BA.5 iterations of the omicron variant doesn’t really boost the body’s immune system to fight off those any more than does the original monovalent vaccine, the study by the Columbia University and University of Michigan researchers found.
“When given as a fourth dose, a bivalent mRNA vaccine targeting Omicron BA.4/BA.5 and an ancestral SARS-CoV-2 strain did not induce superior neutralizing antibody responses in humans … compared to the original monovalent vaccine formulation,” the study states.
As a rationale for doing the study, the researchers note that “despite their widespread use, the impact of a booster shot with a new bivalent vaccine on SARS-CoV-2-neutralizing antibody responses in humans remains unknown.”
The other preprint study, by researchers with the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP), states that research and development must focus on the creation of a COVID-19 vaccine that works against any possible variant that might be thrown at us. A one-and-done vaccine, at least on a yearly basis.
“Advancing a global R&D agenda for broadly protective coronavirus vaccines is a large and complex endeavor that will require ongoing investment, communication, and coordination among researchers; representatives from governments, industry, multilateral and nongovernmental organizations; regulators; and public health policymakers,” the study states. “The purpose of this roadmap is to provide a framework and timeline to align coordination, leadership, and investment to achieve these ambitious goals.”
The study notes that pharmaceutical companies have very little incentive to develop new vaccines. “Unless opportunity costs are absorbed by governments or other funding bodies, companies face a high opportunity cost when it comes to focusing on vaccines rather than other pharmaceuticals with a likely higher per-unit profit, on-going use, and stable demand,” the CIDRAP study states.
The observation comes on the heels of the Biden administration's effort to shift costs for COVID-19 vaccines, treatments and tests to commercial insurance companies, and think tanks such as the Commonwealth Fund start crunching numbers about how much cost payers will have to take on relative to public uptake of vaccines.
In the article on the CIDRAP website, Michael T. Osterholm, Ph.D., CIDRAP’s director, stressed that “the current vaccines should be used. But we need to look at vaccines that address more robust immunity, with a broad breadth of protection.”
The current crop of vaccines will not suffice as society hopefully eases out of the pandemic crisis stage and into one of coexistence not only with the coronaviruses that we know but also the ones that we will come to know. Three coronaviruses have jumped from animal hosts to humans in the last 20 years: COVID-19, or SARS-CoV-2; SARS-CoV-1; and MERS (Middle East respiratory syndrome).
Though COVID-19 is much more infectious than the other two, its case fatality rate stands at about 1%, as opposed to SARS-CoV-1 and MERS, with CFRs of 10% and 35% respectively. “The bigger threat is a future coronavirus that has a case fatality ratio (CFR) approaching that of SARS or MERS, but is as transmissible as COVID-19,” the CIDRAP article states.
Osterholm: “The current vaccines we have for COVID-19 have played a critical role in reducing morbidity and mortality, but they are not the vaccines that will sustain us in the future with coronavirus infections.”
He likened the current vaccines to the first bulky mobile phones that needed to be improved.
In their study, researchers with Columbia University and the University of Michigan collected sera from individuals who’d had three or four doses of the original vaccines, individuals who’d gotten the bivalent vaccine as a fourth dose and individuals infected by the BA.4 or BA.5 subvariants of omicron.
“Boosting with a new bivalent mRNA vaccine targeting both BA.4/BA.5 and an ancestral SARS76 CoV-2 strain did not elicit a discernibly superior virus-neutralizing antibody response compared [to] boosting with an original monovalent vaccine,” the study states. “These findings may be indicative of immunological imprinting, although follow-up studies are needed to determine if the antibody responses will deviate in time, including the impact of a second bivalent booster.”