Testing fractional doses of COVID-19 vaccines

Abstract

Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches.

Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac

“…Due to more rapid waning neutralizing antibody, dose-sparing strategy with intradermal booster vaccination should be used in the setting of inadequate vaccine supply. Fractional doses of COVID-19 vaccines could speed up vaccine coverages and save lives, even with lower efficacy, especially in the era of omicron pandemic [43] .…”

A Randomized Clinical Trial of a Fractional Low Dose of BNT162b2 Booster in Adults Following AZD1222

“…A low-dose BNT162b2 booster after AZD1222 also showed lower adverse events, e.g., fatigue, fever, and local reaction, than the standard-dose booster [16]. Based on the correlation between neutralizing antibody titers and vaccine efficacy against symptomatic infection [17], a model using data from dose-finding trials suggested that half or one-fourth doses of mRNA-1273 have 90 to 95% efficacy, similar to a standard dose [18]. One-third and two-third doses of BNT162b2 also showed predicted efficacy of 70 to 85%, compared with 95% for a standard dose [18].…”

“…Based on the correlation between neutralizing antibody titers and vaccine efficacy against symptomatic infection [17], a model using data from dose-finding trials suggested that half or one-fourth doses of mRNA-1273 have 90 to 95% efficacy, similar to a standard dose [18]. One-third and two-third doses of BNT162b2 also showed predicted efficacy of 70 to 85%, compared with 95% for a standard dose [18]. Using a fractional dosing strategy might ease the limited vaccine supply, thus speeding up vaccine coverage and reducing mortality, even if it yields lower efficacy [18].…”

“…One-third and two-third doses of BNT162b2 also showed predicted efficacy of 70 to 85%, compared with 95% for a standard dose [18]. Using a fractional dosing strategy might ease the limited vaccine supply, thus speeding up vaccine coverage and reducing mortality, even if it yields lower efficacy [18].…”

If You Build it, Will They Vaccinate? The Impact of COVID-19 Vaccine Sites on Vaccination Rates and Outcomes

“…This allocation design has led to discussion on optimal strategies going forward for COVID-19 vaccine and other vaccine distribution for the U.S., and the optimal design of vaccine allocation mechanisms in general (Press, Huisingh-Scheetz, and Arora 2021;Agarwal et al 2021;Cole 2021;Guo et al 2021;Więcek et al 2022).…”