Two of the COVID-19 vaccines currently approved in the US require two doses, administered three to four weeks apart, however, there are few data indicating how best to minimise new infections and hospitalisations with limited vaccine supply and distribution capacity.
A study by Seyed Moghadas at York University in Toronto, Canada, and colleagues suggests that delaying the second dose could improve the effectiveness of vaccine programmes.
The emergence of novel, more contagious SARS-CoV-2 variants has led to a public health debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose, or to prioritize completion of the two-dose series based on tested schedules in clinical trials.
In order to compare the epidemiological impact of each vaccination strategy, researchers built a mathematical model that simulated both COVID-19 transmission and various delayed second dose vaccination schedules. The model simulated several scenarios, including a range of levels of pre-existing immunity in the population and decreased vaccine efficacy of the first dose when followed by a longer interval between doses.
The authors found that delaying the second dose for 9-15 weeks after the first dose avoided more hospitalizations, infections, and deaths compared to following the recommended schedules for Moderna and Pfizer-BioNTech vaccines.
The authors note that the study has several limitations, including a lack of clinical evidence quantifying the durability of the vaccines when administered under different schedules. Researchers thus assumed that protection levels of the first dose were stable if second doses were delayed, and that the protection level after delaying second doses was identical to overall protection after two doses when vaccinating according to schedule. Further studies are needed to pinpoint the optimal time between doses for each type of vaccine.
According to the authors: “When racing against a burgeoning outbreak, our results show that prioritizing vaccine coverage with rapid distribution of the first dose would be critical to mitigating adverse outcomes and allow the healthcare system to also address non-COVID-19 medical needs of the population.”
“We still do not have the full picture of vaccine effectiveness as new and more contagious variants spread. Efficacy of vaccines against these variants is an additional factor that would need to be considered in determining the outcomes of on-time versus delayed second dose and interval between doses,” said Moghadas, the lead author of the study.
“Frozen evolution” of an RNA virus suggests accidental release as a potential cause of arbovirus re-emergence
David J Pascall, Kyriaki Nomikou, Emmanuel Bréard, Stephan Zientara, Ana da Silva Filipe, Bernd Hoffmann, Maude Jacquot, Joshua B Singer, Kris De Clercq, Anette Bøtner, Corinne Sailleau, Cyril Viarouge, Carrie Batten, Giantonella Puggioni, Ciriaco Ligios, Giovanni Savini, Piet A van Rijn, Peter PC Mertens, Roman Biek, Massimo Palmarini
Published in PLOS Biology on 21 April 2021
The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. Bluetongue virus serotype 8 (BTV-8), an arthropod-borne virus of ruminants, emerged in livestock in northern Europe in 2006, spreading to most European countries by 2009 and causing losses of billions of euros. Although the outbreak was successfully controlled through vaccination by early 2010, puzzlingly, a closely related BTV-8 strain re-emerged in France in 2015, triggering a second outbreak that is still ongoing. The origin of this virus and the mechanisms underlying its re-emergence are unknown. Here, we performed phylogenetic analyses of 164 whole BTV-8 genomes sampled throughout the two outbreaks. We demonstrate consistent clock-like virus evolution during both epizootics but found negligible evolutionary change between them. We estimate that the ancestor of the second outbreak dates from the height of the first outbreak in 2008. This implies that the virus had not been replicating for multiple years prior to its re-emergence in 2015. Given the absence of any known natural mechanism that could explain BTV-8 persistence over this long period without replication, we hypothesise that the second outbreak could have been initiated by accidental exposure of livestock to frozen material contaminated with virus from approximately 2008. Our work highlights new targets for pathogen surveillance programmes in livestock and illustrates the power of genomic epidemiology to identify pathways of infectious disease emergence.