key: cord-0786687-qngtk33d
authors: Kanokudom, S.; Assawakosri, S.; suntronwong, N.; Chansaenroj, J.; Auphimai, C.; Nilyanimit, P.; Vichaiwattana, P.; Thongmee, T.; Yorsaeng, R.; Duangchinda, T.; Chantima, W.; Pakchotanon, P.; Srimuan, D.; Thatsanatorn, T.; Klinfueng, S.; Mongkolsapaya, J.; Sudhinaraset, N.; Wanlapakorn, N.; Honsawek, S.; Poovorawan, Y.
title: Comparison of the reactogenicity and immunogenicity of a reduced and standard booster dose of the mRNA COVID-19 vaccine in healthy adults after two doses of inactivated vaccine.
date: 2022-03-02
journal: nan
DOI: 10.1101/2022.03.01.22271735
sha: cb840a29f67d092d7711270f630d2ba6b3bff2b6
doc_id: 786687
cord_uid: qngtk33d

The coronavirus disease 2019 (COVID-19) pandemic has been a serious healthcare problem worldwide since December 2019. The third dose of heterologous vaccine was recently approved by World Health Organization. The present study compared the reactogenicity and immunogenicity of the reduced and standard third booster dose of the BNT162b2 and mRNA-1273 vaccine in adults who previously received the two-dose CoronaVac vaccine. Results showed that headache, joint pain, and diarrhea were more frequent in the 15 g- than the 30 g-BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 g- than the 50 g-mRNA-1273 groups. No significant differences in immunogenicity were detected. These findings demonstrate that the reduced dose of the mRNA vaccines elicited antibody responses against the SARS-CoV-2 delta and omicron variants that were comparable to the standard dose. The reduced dose could be used to increase vaccine coverage in situations of limited global vaccine supply.

• No differences were observed in antibody responses after the reduced or standard booster 37 dose of the mRNA vaccine in CoronaVac-vaccinated adults 38 • Neutralizing antibodies against the delta and omicron variants were significantly higher (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 2, 2022. showed that headache, joint pain, and diarrhea were more frequent in the 15 μg-than the 30 μg-48 BNT162b2 groups, whereas joint pain and chilling were more frequent in the 100 μg-than the 50 49 μg-mRNA-1273 groups. No significant differences in immunogenicity were detected. These (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 2, 2022. ; https://doi.org/10.1101/2022.03.01.22271735 doi: medRxiv preprint 20210910002). Written informed consent was obtained from participants prior to enrollment.

The study was conducted according to the Declaration of Helsinki and the principle of Good The subjects were continuously monitored for local, systemic, and any adverse events 99 (AEs) following immunization (AEFIs) occurring within 7 days using an online or paper-based 100 self-assessment questionnaire. The data collection protocol was given to participants by trained 101 investigators during the initial visit. reduction neutralization test (FRNT50) as previously described [1, 10] . The seropositivity rate of 108 sVNT showed > 30% inhibition, and the seropositivity rate of FRNT50 was > 20-serum dilution.

The assay used to measure the interferon-gamma (IFN-γ) SARS-CoV-2 releasing T cell response 110 was performed on a heparinized whole blood sample as previously described [10] . (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted March 2, 2022. ; https://doi.org/10.1101/2022.03.01.22271735 doi: medRxiv preprint analyses were carried out using GraphPad Prism version 9.3.1. Categorical analyses of age and 116 sex were performed using the Chi-square test. Adverse events were analyzed using the risk 117 difference with a 95% confidence interval (CI). IgG-specific RBDs and FRNT50 were designated 118 as geometric mean titers (GMT) with a 95% CI. Other parameters were presented as medians 119 with interquartile ranges. The differences in antibody titers, S/C, and percentage inhibition and 120 IU/mL minus nil between groups were calculated using the Kruskal-Wallis or Wilcoxon signed-121 rank test (non-parametric) with multiple comparison adjustments. A p-value of <0.05 was 122 considered statistically significant. The most common solicited AE for all groups was injection site pain. Systemic events, 143 including headache and myalgia. headache, joint pain, and diarrhea were more frequent in the 15 144 μg-than the 30 μg-BNT162b2 group, while joint pain and chilling were more frequent in the 100 145 All rights reserved. No reuse allowed without permission.

(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Figure S3 and Table S1 ). There were no significant differences in the (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The T-cell response was compared between the reduced and standard doses of the mRNA 177 vaccines in participants who previously received the two-dose CoronaVac. Results showed that 178 the median IFN-γ CD4+ T cell and CD4+ CD8+ T cell counts were higher at the second visit 179 than at baseline in all groups. By the third visit, IFN-γ CD4+ and CD4+ CD8+ T cell counts 180 were slightly reduced but this was not statistically significant. Importantly, there were no 181 differences in T cell counts between participants receiving the reduced and standard doses of 182 each vaccine ( Figure 4A-B) . (50 μg) [12] . However, the reduced 50 μg-mRNA-1273 vaccine was able to elicit an immune 198 response against the SARS-CoV-2 delta and omicron variants [12] [13] .

In the present study, IFN-γ release was observed by the second visit in participants who (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

Neutralizing activities against the omicron variant after a heterologous booster in healthy 248 adults Receiving Two Doses of CoronaVac Vaccination

Allocation criteria for an initial shortage of a future SARS-CoV-2 vaccine and 251 necessary measures for global immunity

Will the COVID-19 pandemic end with the delta and omicron variants? 254

Breakthrough 256 infections with SARS-CoV-2 omicron despite mRNA vaccine booster dose

Severe breakthrough

COVID-19 cases in the SARS-CoV-2 delta (B.1.617.2) variant era

Immunogenicity and safety of an intradermal BNT162b2 mRNA 263 vaccine booster after two doses of inactivated SARS-CoV-2 vaccine in healthy population

The immunogenicity against variants of concern and reactogenicity of four COVID-19

booster vaccinations following CoronaVac or ChAdOx1 nCoV-19 primary series

Safety and efficacy 270 of the BNT162b2 mRNA Covid-19 vaccine

An mRNA 273 vaccine against SARS-CoV-2 -Preliminary Report

Safety and immunogenicity of the third booster dose with inactivated

Omicron variant neutralization after mRNA-1273 booster vaccination

SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis

COVID-19 vaccination followed by activation of 289 glomerular diseases: does association equal causation?

CoV-2-specific T cells cross-recognize the Omicron variant

All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted March 2, 2022. ; https://doi.org/10.1101/2022.03.01.22271735 doi: medRxiv preprint All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted March 2, 2022. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Table S1 . Patient serum responses during study trials. 345 All rights reserved. No reuse allowed without permission.(which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint this version posted March 2, 2022. ; https://doi.org/10.1101/2022.03.01.22271735 doi: medRxiv preprint