There are benefits to delaying second doses of COVID-19 vaccines, but long-term outcomes depend on strong immunity

Delays in second doses of COVID-19 vaccines should soon reduce case numbers. But the long-term issue burden and the ability for viral “escape” from immunity will depend on the strength of immune responses stemming from natural diseases and one or two vaccine doses, according to a study from Princeton University and McGill University. was published on 9 March. in the magazine Science.

Several countries including the United Kingdom and Canada have said they will delay second doses of COVID-19 vaccines in response to a shortage of supply, but also in an effort to reduce the number of people who are rapidly increasing vaccinations. “

Chadi Saad-Roy, Ph.D. Candidate and Principal Author of Research, Lewis-Sigler Institute for Integrative Genomics, Princeton University

“The initial clinical trials of the vaccines, as well as subsequent epidemiology, are very promising for the effectiveness of the first dose,” said Saad-Roy. long-term immunity from a single dose – or the full two-dose course or natural disease, for that matter – in the long run. “

“All of these will affect future outbreak dynamics,” said co-author Simon Levin, James S. McDonnell’s Distinguished University Professor of Ecology and Evolutionary Biology and an associate faculty member at the High Meadows Environmental Institute (HMEI).

The researchers used a simple model to predict the frequency of COVID-19 cases, as well as the level of population immunity, under a range of vaccine dosing regimens and hypotheses related to immune responses.

“Because the uncertainties in immunology and epidemiology drive these outcomes, simple models are an essential tool for exploring future opportunities,” said lead author Caroline Wagner , assistant professor of bioengineering at McGill University.

“The model, for example, allows for the assumption that immune responses after one dose are weaker than those following a natural infection or two doses,” said co-author Andrea Graham, Princeton professor in evolutionary ecology and biology and an associated faculty member in HMEI. “This seems to be consistent with early reports from countries that have rapidly vaccinated according to a delay schedule. second dose. “

The study found that one-dose strategies could, as expected, reduce the number of cases in the short term by vaccinating a larger number of people faster. However, if immune responses after a single dose are less robust, episodic peaks may be more pronounced.

“More hopefully, we are finding out that as vaccine capacity increases, increasing vaccine levels or changing the dosing regimen may be closer to the recommended two-dose schedule than the epidemiological effects. reduce this long – term, which is important for public health planning, “said Wagner.

Another important outcome associated with incomplete immune responses is the ability to escape viral immunity. To begin addressing this complex issue, the authors modified an existing simple ‘phylodynamic’ model for the escape of viral immunity developed by co-authors Bryan Grenfell, the Kathryn Briger and Sarah Fenton Professor of Evolutionary Ecology and Biology and Public Affairs; Oliver G. Pybus, professor of evolution and infectious disease at Oxford University; and Edward C. Holmes, ARC Australian Laureate Fellow and professor at the University of Sydney; along with other colleagues not currently involved in the work.

The escape theory of viral immunity predicts that moderate selective stress in individuals with partial immunity, combined with adequate viral transmission, may lead to viral evolution. Here, the authors examine this potential along with a range of other scenarios, including the more promising case of minimal potential for change in hosts with weak immunity after doses. one or two vaccines.

“At least one variable has already emerged that could be adjusted for partial protective escape,” Holmes said.

“A simple theory confirms that the evolution and spread of changes by infectious hosts with moderate levels of immunity may be important,” said Grenfell, an associate faculty member at HMEI. and the duration of immunity, and in particular the effect of these on repeats, are key parameters to be determined. “

“Our results are largely dependent on the strength of immune responses after one and two vaccine doses, but ultimately these clinical parameters are largely unknown,” explained co-author Michael Mina, senior. assistant professor at Harvard School of Public Health and Harvard Medical School.

“Moving forward, a better grip on these will be essential to make strong public policy decisions,” Mina said. “We suggest that randomized early dose times in vaccination campaigns and careful monitoring may be necessary. on viral loads and immune markers in vaccinated individuals as well as those with natural diseases and their binders have been important means of doing so. “

One intuitive finding that the paper confirms is that very low levels of vaccine administration are associated with larger case numbers and, possibly, a higher potential for viral conversion.

“This strongly reinforces the importance of global vaccine circulation, as immune escape in one place spreads rapidly,” said C. Jessica E. Metcalf, associate professor in ec and evolutionary biology and public affairs at Princeton, as well as an associate faculty member at HMEI.

“The models are relatively simple in concept, but they illustrate the complexity of the problem and highlight the challenges that lie ahead,” said Michael Boots, professor of integrated biology at UC. Berkeley was not involved in the study. ”This important piece of work provides a framework that we can use to inform our ongoing approach and further identifies the key issues. information gaps we need to address. “