TY - JOUR
T1 - Antibody Responses and Reactogenicity of a Heterologous, Full-Dose Messenger RNA-1273 Booster in Heavily SARS-CoV-2-Exposed CoronaVac-Vaccinated Health-Care Workers in Indonesia
T2 - A Real-World Observational Study
AU - Sinto, Robert
AU - Utomo, Dwi
AU - Suwarti,
AU - Nelwan, Erni J.
AU - Surendra, Henry
AU - Natasha, Cindy
AU - Fransiska,
AU - Theresia, Deborah
AU - Ranitria, Adella Faiqa
AU - Subekti, Decy
AU - Nuraeni, Nunung
AU - Handayani, Winahyu
AU - Rahardjani, Mutia
AU - Baird, J. Kevin
AU - Dunachie, Susanna
AU - Shankar, Anuraj H.
AU - Hamers, Raph L.
N1 - Funding Information:
Financial support: This work was funded by the Wellcome Trust, UK (106680/Z/14/Z and 222574/Z/21/Z). S. D. is funded by a National Institute for Health and Care Research Global Research Professorship (NIHR300791). The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Funding Information:
We thank the study participants, the staff at the collaborating clinical sites, and Prodia Clinical Laboratory in Jakarta. The American Society of Tropical Medicine and Hygiene has waived the open-access fee for this article due to the ongoing COVID-19 pandemic.
Publisher Copyright:
Copyright © 2023 The author(s)
PY - 2023/1
Y1 - 2023/1
N2 - Real-world data on heterologous boosting with messenger RNA (mRNA)-1273 (Moderna) after inactivated COVID-19 vaccination are limited. We report mRNA-1273 boosting in heavily SARS-CoV-2-exposed Indonesian healthcare workers who received a two-dose CoronaVac 6 months prior. Between August and November 2021, we measured SARS-CoV-2 spike-specific IgG binding antibody (Bab) titers in all 304 participants, and neutralizing antibody titers in a random subset of 71 participants, on stored paired serum samples taken before and 28 days after a full-dose (100-mg) mRNA-1273 booster. At the time of the mRNA-1273 boost, 107 participants (35.2%) were not previously infected (naive vaccinated), 42 (13.8%) were infected before CoronaVac (infected vaccinated), and 155 (51.0%) were infected after CoronaVac (mostly during the Delta wave; vaccinated infected). At time of the mRNA-1273 boost, neutralizing antibodies could still be detected in 83% of participants (59 of 71) overall, 60% of naive-vaccinated participants (15 of 25), 95.7% of vaccinated-infected participants (22 of 23), and 95.7% of infected vaccinated participants (22 of 23). After the mRNA-1273 boost, 100% of participants (71 of 71) had neutralizing antibody activity, with increases in median Bab and neutralizing antibody serum titers of 9.3- and 27.0-fold overall, 89.1- and 2,803.4-fold in naive-vaccinated participants, 15.9- and 19.9-fold in infected-vaccinated participants, and 2.2- and 18.4-fold in vaccinated-infected participants. In the multivariable analysis, Bab titers after the mRNA-1273 boost were greatest in individuals who had a previous virus breakthrough post-CoronaVac, and when a longer time period (. 4 months) had elapsed since the most recent prior “spike antigen exposure” (either second CoronaVac or virus breakthrough). Overall, adverse reactions were mild and short-lived. In conclusion, a full-dose mRNA-1273 booster after CoronaVac was well tolerated and immunogenic after 28 days, including in those with very low antibody levels.
AB - Real-world data on heterologous boosting with messenger RNA (mRNA)-1273 (Moderna) after inactivated COVID-19 vaccination are limited. We report mRNA-1273 boosting in heavily SARS-CoV-2-exposed Indonesian healthcare workers who received a two-dose CoronaVac 6 months prior. Between August and November 2021, we measured SARS-CoV-2 spike-specific IgG binding antibody (Bab) titers in all 304 participants, and neutralizing antibody titers in a random subset of 71 participants, on stored paired serum samples taken before and 28 days after a full-dose (100-mg) mRNA-1273 booster. At the time of the mRNA-1273 boost, 107 participants (35.2%) were not previously infected (naive vaccinated), 42 (13.8%) were infected before CoronaVac (infected vaccinated), and 155 (51.0%) were infected after CoronaVac (mostly during the Delta wave; vaccinated infected). At time of the mRNA-1273 boost, neutralizing antibodies could still be detected in 83% of participants (59 of 71) overall, 60% of naive-vaccinated participants (15 of 25), 95.7% of vaccinated-infected participants (22 of 23), and 95.7% of infected vaccinated participants (22 of 23). After the mRNA-1273 boost, 100% of participants (71 of 71) had neutralizing antibody activity, with increases in median Bab and neutralizing antibody serum titers of 9.3- and 27.0-fold overall, 89.1- and 2,803.4-fold in naive-vaccinated participants, 15.9- and 19.9-fold in infected-vaccinated participants, and 2.2- and 18.4-fold in vaccinated-infected participants. In the multivariable analysis, Bab titers after the mRNA-1273 boost were greatest in individuals who had a previous virus breakthrough post-CoronaVac, and when a longer time period (. 4 months) had elapsed since the most recent prior “spike antigen exposure” (either second CoronaVac or virus breakthrough). Overall, adverse reactions were mild and short-lived. In conclusion, a full-dose mRNA-1273 booster after CoronaVac was well tolerated and immunogenic after 28 days, including in those with very low antibody levels.
UR - http://www.scopus.com/inward/record.url?scp=85146324545&partnerID=8YFLogxK
U2 - 10.4269/ajtmh.22-0256
DO - 10.4269/ajtmh.22-0256
M3 - Article
AN - SCOPUS:85146324545
SN - 0002-9637
VL - 108
SP - 115
EP - 123
JO - American Journal of Tropical Medicine and Hygiene
JF - American Journal of Tropical Medicine and Hygiene
IS - 1
ER -