https://www.nature.com/articles/d41586-021-01893-0 Skip to main content Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Advertisement Advertisement Nature * View all journals * Search * My Account Login * Explore content * Journal information * Publish with us Subscribe * Sign up for alerts * RSS feed 1. nature 2. news 3. article * NEWS * 09 July 2021 Quarter-dose of Moderna COVID vaccine still rouses a big immune response Results hint that dose stretching could help to address the world's acute vaccine shortage.' * Elie Dolgin ^0 1. Elie Dolgin 1. Elie Dolgin is a science journalist in Somerville, Massachusetts. View author publications You can also search for this author in PubMed Google Scholar * Share on Twitter * Share on Facebook * Share via E-Mail You have full access to this article via your institution. Download PDF Three health workers fill syringes with the Moderna COVID-19 vaccine at a vaccination center in Tokyo. Workers prepare doses of Moderna's COVID-19 vaccine.Credit: Eugene Hoshiko/AP/Shutterstock A little bit of coronavirus vaccine goes a long way towards generating lasting immunity. Two jabs that each contained only one-quarter of the standard dose of the Moderna COVID vaccine gave rise to long-lasting protective antibodies and virus-fighting T cells, according to tests in nearly three dozen people^1. The results hint at the possibility of administering fractional doses to stretch limited vaccine supplies and accelerate the global immunization effort. Since 2016, such a dose-reduction strategy has successfully vaccinated millions of people in Africa and South America against yellow fever^2. But no similar approach has been tried in response to COVID-19, despite vaccine shortages in much of the global south. "There's a huge status quo bias, and it's killing people," says Alex Tabarrok, an economist at George Mason University in Fairfax, Virginia. "Had we done this starting in January, we could have vaccinated tens, perhaps hundreds, of millions more people." The just-right dose? In the earliest trial of Moderna's mRNA-based vaccine, study participants received one of three dose levels: 25, 100 or 250 micrograms^3. The top dose proved too toxic. The low dose elicited the weakest immune response. The middle dose seemed to offer the best balance: it triggered strong immunity and had acceptable side effects. That 100-microgram dose ultimately became the one authorized for mass use in dozens of countries. But Moderna scientists later showed that a half-dose seemed to be just as good as the standard dose at stimulating immune protection^4. To find out whether a low dose might offer protection, scientists analysed blood from 35 participants in the original trial. Each had received two 25-microgram jabs of vaccine 28 days apart. Six months after the second shot, nearly all of the 35 participants had 'neutralizing' antibodies, which block the virus from infecting cells, the researchers reported in a preprint published on 5 July^1. Participants' blood also contained an armada of different T cells, both 'killer' cells that can destroy infected cells and a variety of 'helper' cells that aid in general immune defence. [d41586-021] Had COVID? You'll probably make antibodies for a lifetime Levels of both antibodies and T cells were comparable to those found in people who have recovered from COVID-19. "It is quite remarkable -- and quite promising -- that you can easily detect responses for that long a time," says Daniela Weiskopf, an immunologist at the La Jolla Institute for Immunology (LJI) in California and a co-author of the study, which has not yet been peer reviewed. Corine Geurts van Kessel, a clinical virologist at the Erasmus University Medical Center in Rotterdam, the Netherlands, who was not involved in the study, agrees. "It's rather good news," she says. "Even with a low dose, you can prime your own immune system in quite a nice way." Weiskopf and her study co-author Shane Crotty, also at LJI, are among the scientists who would prefer carefully planned trials to confirm the efficacy of reduced vaccine doses before any such regimen is widely deployed. One such trial is ongoing: a study in Belgium is comparing a lower-dose version of the vaccine from Pfizer-BioNTech against the standard dose. But Sarah Cobey, an infectious-disease researcher at the University of Chicago in Illinois and a co-author of a 5 July Nature Medicine commentary^5 supporting dose 'fractionation', disagrees about the need for time-consuming data collection. "We shouldn't wait that long," she says. "People are dying, and we have historical precedent for making very well-reasoned guesses that we think are going to save lives." Less is more Even if the immune responses spurred by the low-dose strategy are only moderately effective at keeping SARS-CoV-2 at bay, it could still be worth giving quarter doses to speed up the pace of vaccination around the world, argues Tabarrok. According to a modelling study published by Tabarrok and other economists, such an approach would reduce infections and COVID-linked deaths more than current policies^6. The study has not yet been peer reviewed. A half-dose now is more useful to an unvaccinated person than a full dose a year from now, Tabarrok says, which means that dose-stretching "is a way of promoting vaccine equity." doi: https://doi.org/10.1038/d41586-021-01893-0 References 1. 1. Mateus, J. et al. Preprint at medRxiv https://doi.org/10.1101/ 2021.06.30.21259787 (2021). 2. 2. Casey, R. M. et al. N. Engl. J. Med. 381, 444-454 (2019). PubMed Article Google Scholar 3. 3. Jackson, L. A. et al. N. Engl. J. Med. 383, 1920-1931 (2020). PubMed Article Google Scholar 4. 4. Chu, L. et al. Vaccine 39, 2791-2799 (2021). PubMed Article Google Scholar 5. 5. Cowling, B. J. et al. Nature Med. https://doi.org/10.1038/ s41591-021-01440-4 (2021). PubMed Article Google Scholar 6. 6. Wiecek, W. et al. Preprint at SSRN https://doi.org/10.2139/ ssrn.3864485 (2021). Download references Related Articles * [d41586-021] How can countries stretch COVID vaccine supplies? 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Email address [ ] [ ] Yes! Sign me up to receive the daily Nature Briefing email. I agree my information will be processed in accordance with the Nature and Springer Nature Limited Privacy Policy. Sign up You have full access to this article via your institution. Download PDF Related Articles * [d41586-021] How can countries stretch COVID vaccine supplies? Scientists are divided over dosing strategies * [d41586-021] 'Unprecedented achievement': who received the first billion COVID vaccinations? * [d41586-021] Is one vaccine dose enough if you've had COVID? What the science says * [d41586-021] Mounting evidence suggests Sputnik COVID vaccine is safe and effective * [d41586-021] Six months of COVID vaccines: what 1.7 billion doses have taught scientists Subjects * SARS-CoV-2 * Vaccines * Medical research * Public health * Immunology * Infection Advertisement Sign up to Nature Briefing An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday. 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