Testing Fractional doses of COVID-19 Vaccines

Abstract

and the Economy conference for helpful comments. This work was supported in part by the Wellspring Philanthropic Fund (Grant No: 15104) and Open Philanthropy. Więcek provides scientific consultancy for Certara, a drug development company and 1 Day Sooner, a COVID-19 human challenge trial advocacy group. Więcek reports no material conflicts of interest with regards to development of COVID-19 vaccines. Michael Kremer is the Faculty Director of the Development Innovation Lab (DIL) at the University of Chicago. Więcek is a Consulting Director at DIL. The views expressed herein are those of the authors and do not necessarily reflect the views of the National Bureau of Economic Research.NBER working papers are circulated for discussion and comment purposes. They have not been peer-reviewed or been subject to the review by the NBER Board of Directors that accompanies official NBER publications.

Safety and immunogenicity of a reduced dose of the BNT162b2 mRNA COVID-19 vaccine (REDU-VAC): a single blind, randomized, non-inferiority trial

“…The study results show that the administration of a reduced dose (2x20µg) of the mRNA vaccine BNT162b2 (12,20). We therefore argue that the moderately lower humoral response of the reduced dose regimen investigated in our study is still excellent, and likely provides significant protection against COVID-19 with additional benefit as compared to the non-mRNA vaccines currently in use in most low and middle-income countries (13,14). Larger immunogenicity and effectiveness trials are warranted to support this notion.…”

“…Despite ChadOx1 nCoV-19’s markedly lower humoral responses, it still has been shown to have an efficacy against symptomatic infection of about 70%, and it has been approved for use in 182 countries with more than two billion doses administered, primarily in LIC (12, 20). We therefore argue that the moderately lower humoral response of the reduced dose regimen investigated in our study is still excellent, and likely provides significant protection against COVID-19 with additional benefit as compared to the non-mRNA vaccines currently in use in most low and middle-income countries (13, 14). Larger immunogenicity and effectiveness trials are warranted to support this notion.…”

“…This multicentre trial observed 67%-97% efficacy of protection against symptomatic COVID-19 in a sub-group of participants who were primed with a half dose and boosted with a full dose of the ChAdOx1 nCoV-19 (Vaxzevria®, AstraZeneca) vaccine (12). In a recent paper, Więcek et al used modelling data by Khoury et al to predict vaccine efficacy of fractional doses (13, 14). Compared to the 95% efficacy provided by the full dose of 30µg, fractional doses of 10µg and 20µg of BNT162b2 are estimated to still be 80-90% effective in adults below 55 years old.…”

Expanding Capacity for Vaccines Against Covid-19 and Future Pandemics: A Review of Economic Issues

“…For Covid-19 vaccines, evidence from clinical trials suggests that lower doses of certain vaccines produce strong immune responses (as measured by neutralizing antibodies), especially against the original strain of the virus. Combined with early research on correlates of immunity, this evidence suggests that 1/2 or even 1/4 doses of some vaccines could be highly effective-possibly even more effective than full doses in some cases (Więcek et al 2022).…”

“…Yet the vaccination rate in low-income countries remained low deep into the pandemic (Agarwal and Reed 2022). While Ahuja et al (2022) can rationalize why low-income countries did not invest at risk, it does not rationalize persistently low vaccine purchases. The tiny benefit of an at-risk investment program to the average low-income country estimated by Ahuja et al (2021), 30 cents per capita, vastly understates the gain from eventually purchasing vaccines there.…”